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• Palgrave's Study Guide to Carrying Out a Literature Review Your research is seen as a contribution to knowledge in the field and it needs to indicate, therefore, that there is an awareness of what that knowledge comprises. Read this guide to getting started.
• Purdue OWL's Guide to Writing a Literature Review A literature review requires the writer to perform extensive research on published work in one’s field in order to explain how one’s own work fits into the larger conversation regarding a particular topic. This task requires the writer to spend time reading, managing, and conveying information; the complexity of literature reviews can make this section one of the most challenging parts of writing about one’s research. This handout will provide some strategies for revising literature reviews.

Every time you conduct research, you will need to make it clear where you got your evidence from. This work of citing our sources is absolutely essential for a couple of reasons.

• It demonstrates to the readers of our own research that we have evidence to back up our claims.
• A complete and correct citation directs readers to the original source for them to verify our claims and learn more.
• It gives credit to the researchers whose intellectual work helped form our own research.
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• 04 December 2020
• Correction 09 December 2020

How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

You can also search for this author in PubMed   Google Scholar

Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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doi: https://doi.org/10.1038/d41586-020-03422-x

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Correction 09 December 2020 : An earlier version of the tables in this article included some incorrect details about the programs Zotero, Endnote and Manubot. These have now been corrected.

Hsing, I.-M., Xu, Y. & Zhao, W. Electroanalysis 19 , 755–768 (2007).

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Ledesma, H. A. et al. Nature Nanotechnol. 14 , 645–657 (2019).

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Brahlek, M., Koirala, N., Bansal, N. & Oh, S. Solid State Commun. 215–216 , 54–62 (2015).

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• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

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What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
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What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

• Provide a comprehensive and updated review of the literature;
• Explain why this review has taken place;
• Articulate a position or hypothesis;
• Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

• Demonstrate how a study fills a gap in research
• Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

• Organizes or describes a topic
• Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

• It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
• It may be too focused. Some niche studies may miss the bigger picture.
• It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
• It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

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Susan Macicak : Linguistics

Imelda Vetter : Dell Medical School

For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

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A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

• Give a new interpretation of old material or combine new with old interpretations,
• Trace the intellectual progression of the field, including major debates,
• Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
• Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

• Place each work in the context of its contribution to understanding the research problem being studied.
• Describe the relationship of each work to the others under consideration.
• Identify new ways to interpret prior research.
• Reveal any gaps that exist in the literature.
• Resolve conflicts amongst seemingly contradictory previous studies.
• Identify areas of prior scholarship to prevent duplication of effort.
• Point the way in fulfilling a need for additional research.
• Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE: Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

• An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
• Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
• An explanation of how each work is similar to and how it varies from the others,
• Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

• Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
• Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
• Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
• Persuasiveness -- which of the author's theses are most convincing or least convincing?
• Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

• Current Situation : Information necessary to understand the current topic or focus of the literature review.
• Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
• History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
• Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
• Standards : Description of the way in which you present your information.
• Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

• Sources in your literature review do not clearly relate to the research problem;
• You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
• Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
• Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
• Does not describe the search procedures that were used in identifying the literature to review;
• Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
• Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

• How are they organizing their ideas?
• What methods have they used to study the problem?
• What theories have been used to explain, predict, or understand their research problem?
• What sources have they cited to support their conclusions?
• How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

• Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
• Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
• Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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• v.21(3); Fall 2022

Literature Reviews, Theoretical Frameworks, and Conceptual Frameworks: An Introduction for New Biology Education Researchers

Julie a. luft.

† Department of Mathematics, Social Studies, and Science Education, Mary Frances Early College of Education, University of Georgia, Athens, GA 30602-7124

Sophia Jeong

‡ Department of Teaching & Learning, College of Education & Human Ecology, Ohio State University, Columbus, OH 43210

Robert Idsardi

§ Department of Biology, Eastern Washington University, Cheney, WA 99004

Grant Gardner

∥ Department of Biology, Middle Tennessee State University, Murfreesboro, TN 37132

Associated Data

To frame their work, biology education researchers need to consider the role of literature reviews, theoretical frameworks, and conceptual frameworks as critical elements of the research and writing process. However, these elements can be confusing for scholars new to education research. This Research Methods article is designed to provide an overview of each of these elements and delineate the purpose of each in the educational research process. We describe what biology education researchers should consider as they conduct literature reviews, identify theoretical frameworks, and construct conceptual frameworks. Clarifying these different components of educational research studies can be helpful to new biology education researchers and the biology education research community at large in situating their work in the broader scholarly literature.

INTRODUCTION

Discipline-based education research (DBER) involves the purposeful and situated study of teaching and learning in specific disciplinary areas ( Singer et al. , 2012 ). Studies in DBER are guided by research questions that reflect disciplines’ priorities and worldviews. Researchers can use quantitative data, qualitative data, or both to answer these research questions through a variety of methodological traditions. Across all methodologies, there are different methods associated with planning and conducting educational research studies that include the use of surveys, interviews, observations, artifacts, or instruments. Ensuring the coherence of these elements to the discipline’s perspective also involves situating the work in the broader scholarly literature. The tools for doing this include literature reviews, theoretical frameworks, and conceptual frameworks. However, the purpose and function of each of these elements is often confusing to new education researchers. The goal of this article is to introduce new biology education researchers to these three important elements important in DBER scholarship and the broader educational literature.

The first element we discuss is a review of research (literature reviews), which highlights the need for a specific research question, study problem, or topic of investigation. Literature reviews situate the relevance of the study within a topic and a field. The process may seem familiar to science researchers entering DBER fields, but new researchers may still struggle in conducting the review. Booth et al. (2016b) highlight some of the challenges novice education researchers face when conducting a review of literature. They point out that novice researchers struggle in deciding how to focus the review, determining the scope of articles needed in the review, and knowing how to be critical of the articles in the review. Overcoming these challenges (and others) can help novice researchers construct a sound literature review that can inform the design of the study and help ensure the work makes a contribution to the field.

The second and third highlighted elements are theoretical and conceptual frameworks. These guide biology education research (BER) studies, and may be less familiar to science researchers. These elements are important in shaping the construction of new knowledge. Theoretical frameworks offer a way to explain and interpret the studied phenomenon, while conceptual frameworks clarify assumptions about the studied phenomenon. Despite the importance of these constructs in educational research, biology educational researchers have noted the limited use of theoretical or conceptual frameworks in published work ( DeHaan, 2011 ; Dirks, 2011 ; Lo et al. , 2019 ). In reviewing articles published in CBE—Life Sciences Education ( LSE ) between 2015 and 2019, we found that fewer than 25% of the research articles had a theoretical or conceptual framework (see the Supplemental Information), and at times there was an inconsistent use of theoretical and conceptual frameworks. Clearly, these frameworks are challenging for published biology education researchers, which suggests the importance of providing some initial guidance to new biology education researchers.

Fortunately, educational researchers have increased their explicit use of these frameworks over time, and this is influencing educational research in science, technology, engineering, and mathematics (STEM) fields. For instance, a quick search for theoretical or conceptual frameworks in the abstracts of articles in Educational Research Complete (a common database for educational research) in STEM fields demonstrates a dramatic change over the last 20 years: from only 778 articles published between 2000 and 2010 to 5703 articles published between 2010 and 2020, a more than sevenfold increase. Greater recognition of the importance of these frameworks is contributing to DBER authors being more explicit about such frameworks in their studies.

Collectively, literature reviews, theoretical frameworks, and conceptual frameworks work to guide methodological decisions and the elucidation of important findings. Each offers a different perspective on the problem of study and is an essential element in all forms of educational research. As new researchers seek to learn about these elements, they will find different resources, a variety of perspectives, and many suggestions about the construction and use of these elements. The wide range of available information can overwhelm the new researcher who just wants to learn the distinction between these elements or how to craft them adequately.

Our goal in writing this paper is not to offer specific advice about how to write these sections in scholarly work. Instead, we wanted to introduce these elements to those who are new to BER and who are interested in better distinguishing one from the other. In this paper, we share the purpose of each element in BER scholarship, along with important points on its construction. We also provide references for additional resources that may be beneficial to better understanding each element. Table 1 summarizes the key distinctions among these elements.

Comparison of literature reviews, theoretical frameworks, and conceptual reviews

This article is written for the new biology education researcher who is just learning about these different elements or for scientists looking to become more involved in BER. It is a result of our own work as science education and biology education researchers, whether as graduate students and postdoctoral scholars or newly hired and established faculty members. This is the article we wish had been available as we started to learn about these elements or discussed them with new educational researchers in biology.

LITERATURE REVIEWS

Purpose of a literature review.

A literature review is foundational to any research study in education or science. In education, a well-conceptualized and well-executed review provides a summary of the research that has already been done on a specific topic and identifies questions that remain to be answered, thus illustrating the current research project’s potential contribution to the field and the reasoning behind the methodological approach selected for the study ( Maxwell, 2012 ). BER is an evolving disciplinary area that is redefining areas of conceptual emphasis as well as orientations toward teaching and learning (e.g., Labov et al. , 2010 ; American Association for the Advancement of Science, 2011 ; Nehm, 2019 ). As a result, building comprehensive, critical, purposeful, and concise literature reviews can be a challenge for new biology education researchers.

Building Literature Reviews

There are different ways to approach and construct a literature review. Booth et al. (2016a) provide an overview that includes, for example, scoping reviews, which are focused only on notable studies and use a basic method of analysis, and integrative reviews, which are the result of exhaustive literature searches across different genres. Underlying each of these different review processes are attention to the s earch process, a ppraisa l of articles, s ynthesis of the literature, and a nalysis: SALSA ( Booth et al. , 2016a ). This useful acronym can help the researcher focus on the process while building a specific type of review.

However, new educational researchers often have questions about literature reviews that are foundational to SALSA or other approaches. Common questions concern determining which literature pertains to the topic of study or the role of the literature review in the design of the study. This section addresses such questions broadly while providing general guidance for writing a narrative literature review that evaluates the most pertinent studies.

The literature review process should begin before the research is conducted. As Boote and Beile (2005 , p. 3) suggested, researchers should be “scholars before researchers.” They point out that having a good working knowledge of the proposed topic helps illuminate avenues of study. Some subject areas have a deep body of work to read and reflect upon, providing a strong foundation for developing the research question(s). For instance, the teaching and learning of evolution is an area of long-standing interest in the BER community, generating many studies (e.g., Perry et al. , 2008 ; Barnes and Brownell, 2016 ) and reviews of research (e.g., Sickel and Friedrichsen, 2013 ; Ziadie and Andrews, 2018 ). Emerging areas of BER include the affective domain, issues of transfer, and metacognition ( Singer et al. , 2012 ). Many studies in these areas are transdisciplinary and not always specific to biology education (e.g., Rodrigo-Peiris et al. , 2018 ; Kolpikova et al. , 2019 ). These newer areas may require reading outside BER; fortunately, summaries of some of these topics can be found in the Current Insights section of the LSE website.

In focusing on a specific problem within a broader research strand, a new researcher will likely need to examine research outside BER. Depending upon the area of study, the expanded reading list might involve a mix of BER, DBER, and educational research studies. Determining the scope of the reading is not always straightforward. A simple way to focus one’s reading is to create a “summary phrase” or “research nugget,” which is a very brief descriptive statement about the study. It should focus on the essence of the study, for example, “first-year nonmajor students’ understanding of evolution,” “metacognitive prompts to enhance learning during biochemistry,” or “instructors’ inquiry-based instructional practices after professional development programming.” This type of phrase should help a new researcher identify two or more areas to review that pertain to the study. Focusing on recent research in the last 5 years is a good first step. Additional studies can be identified by reading relevant works referenced in those articles. It is also important to read seminal studies that are more than 5 years old. Reading a range of studies should give the researcher the necessary command of the subject in order to suggest a research question.

Given that the research question(s) arise from the literature review, the review should also substantiate the selected methodological approach. The review and research question(s) guide the researcher in determining how to collect and analyze data. Often the methodological approach used in a study is selected to contribute knowledge that expands upon what has been published previously about the topic (see Institute of Education Sciences and National Science Foundation, 2013 ). An emerging topic of study may need an exploratory approach that allows for a description of the phenomenon and development of a potential theory. This could, but not necessarily, require a methodological approach that uses interviews, observations, surveys, or other instruments. An extensively studied topic may call for the additional understanding of specific factors or variables; this type of study would be well suited to a verification or a causal research design. These could entail a methodological approach that uses valid and reliable instruments, observations, or interviews to determine an effect in the studied event. In either of these examples, the researcher(s) may use a qualitative, quantitative, or mixed methods methodological approach.

Even with a good research question, there is still more reading to be done. The complexity and focus of the research question dictates the depth and breadth of the literature to be examined. Questions that connect multiple topics can require broad literature reviews. For instance, a study that explores the impact of a biology faculty learning community on the inquiry instruction of faculty could have the following review areas: learning communities among biology faculty, inquiry instruction among biology faculty, and inquiry instruction among biology faculty as a result of professional learning. Biology education researchers need to consider whether their literature review requires studies from different disciplines within or outside DBER. For the example given, it would be fruitful to look at research focused on learning communities with faculty in STEM fields or in general education fields that result in instructional change. It is important not to be too narrow or too broad when reading. When the conclusions of articles start to sound similar or no new insights are gained, the researcher likely has a good foundation for a literature review. This level of reading should allow the researcher to demonstrate a mastery in understanding the researched topic, explain the suitability of the proposed research approach, and point to the need for the refined research question(s).

The literature review should include the researcher’s evaluation and critique of the selected studies. A researcher may have a large collection of studies, but not all of the studies will follow standards important in the reporting of empirical work in the social sciences. The American Educational Research Association ( Duran et al. , 2006 ), for example, offers a general discussion about standards for such work: an adequate review of research informing the study, the existence of sound and appropriate data collection and analysis methods, and appropriate conclusions that do not overstep or underexplore the analyzed data. The Institute of Education Sciences and National Science Foundation (2013) also offer Common Guidelines for Education Research and Development that can be used to evaluate collected studies.

Because not all journals adhere to such standards, it is important that a researcher review each study to determine the quality of published research, per the guidelines suggested earlier. In some instances, the research may be fatally flawed. Examples of such flaws include data that do not pertain to the question, a lack of discussion about the data collection, poorly constructed instruments, or an inadequate analysis. These types of errors result in studies that are incomplete, error-laden, or inaccurate and should be excluded from the review. Most studies have limitations, and the author(s) often make them explicit. For instance, there may be an instructor effect, recognized bias in the analysis, or issues with the sample population. Limitations are usually addressed by the research team in some way to ensure a sound and acceptable research process. Occasionally, the limitations associated with the study can be significant and not addressed adequately, which leaves a consequential decision in the hands of the researcher. Providing critiques of studies in the literature review process gives the reader confidence that the researcher has carefully examined relevant work in preparation for the study and, ultimately, the manuscript.

A solid literature review clearly anchors the proposed study in the field and connects the research question(s), the methodological approach, and the discussion. Reviewing extant research leads to research questions that will contribute to what is known in the field. By summarizing what is known, the literature review points to what needs to be known, which in turn guides decisions about methodology. Finally, notable findings of the new study are discussed in reference to those described in the literature review.

Within published BER studies, literature reviews can be placed in different locations in an article. When included in the introductory section of the study, the first few paragraphs of the manuscript set the stage, with the literature review following the opening paragraphs. Cooper et al. (2019) illustrate this approach in their study of course-based undergraduate research experiences (CUREs). An introduction discussing the potential of CURES is followed by an analysis of the existing literature relevant to the design of CUREs that allows for novel student discoveries. Within this review, the authors point out contradictory findings among research on novel student discoveries. This clarifies the need for their study, which is described and highlighted through specific research aims.

A literature reviews can also make up a separate section in a paper. For example, the introduction to Todd et al. (2019) illustrates the need for their research topic by highlighting the potential of learning progressions (LPs) and suggesting that LPs may help mitigate learning loss in genetics. At the end of the introduction, the authors state their specific research questions. The review of literature following this opening section comprises two subsections. One focuses on learning loss in general and examines a variety of studies and meta-analyses from the disciplines of medical education, mathematics, and reading. The second section focuses specifically on LPs in genetics and highlights student learning in the midst of LPs. These separate reviews provide insights into the stated research question.

Suggestions and Advice

A well-conceptualized, comprehensive, and critical literature review reveals the understanding of the topic that the researcher brings to the study. Literature reviews should not be so big that there is no clear area of focus; nor should they be so narrow that no real research question arises. The task for a researcher is to craft an efficient literature review that offers a critical analysis of published work, articulates the need for the study, guides the methodological approach to the topic of study, and provides an adequate foundation for the discussion of the findings.

In our own writing of literature reviews, there are often many drafts. An early draft may seem well suited to the study because the need for and approach to the study are well described. However, as the results of the study are analyzed and findings begin to emerge, the existing literature review may be inadequate and need revision. The need for an expanded discussion about the research area can result in the inclusion of new studies that support the explanation of a potential finding. The literature review may also prove to be too broad. Refocusing on a specific area allows for more contemplation of a finding.

It should be noted that there are different types of literature reviews, and many books and articles have been written about the different ways to embark on these types of reviews. Among these different resources, the following may be helpful in considering how to refine the review process for scholarly journals:

• Booth, A., Sutton, A., & Papaioannou, D. (2016a). Systemic approaches to a successful literature review (2nd ed.). Los Angeles, CA: Sage. This book addresses different types of literature reviews and offers important suggestions pertaining to defining the scope of the literature review and assessing extant studies.
• Booth, W. C., Colomb, G. G., Williams, J. M., Bizup, J., & Fitzgerald, W. T. (2016b). The craft of research (4th ed.). Chicago: University of Chicago Press. This book can help the novice consider how to make the case for an area of study. While this book is not specifically about literature reviews, it offers suggestions about making the case for your study.
• Galvan, J. L., & Galvan, M. C. (2017). Writing literature reviews: A guide for students of the social and behavioral sciences (7th ed.). Routledge. This book offers guidance on writing different types of literature reviews. For the novice researcher, there are useful suggestions for creating coherent literature reviews.

THEORETICAL FRAMEWORKS

Purpose of theoretical frameworks.

As new education researchers may be less familiar with theoretical frameworks than with literature reviews, this discussion begins with an analogy. Envision a biologist, chemist, and physicist examining together the dramatic effect of a fog tsunami over the ocean. A biologist gazing at this phenomenon may be concerned with the effect of fog on various species. A chemist may be interested in the chemical composition of the fog as water vapor condenses around bits of salt. A physicist may be focused on the refraction of light to make fog appear to be “sitting” above the ocean. While observing the same “objective event,” the scientists are operating under different theoretical frameworks that provide a particular perspective or “lens” for the interpretation of the phenomenon. Each of these scientists brings specialized knowledge, experiences, and values to this phenomenon, and these influence the interpretation of the phenomenon. The scientists’ theoretical frameworks influence how they design and carry out their studies and interpret their data.

Within an educational study, a theoretical framework helps to explain a phenomenon through a particular lens and challenges and extends existing knowledge within the limitations of that lens. Theoretical frameworks are explicitly stated by an educational researcher in the paper’s framework, theory, or relevant literature section. The framework shapes the types of questions asked, guides the method by which data are collected and analyzed, and informs the discussion of the results of the study. It also reveals the researcher’s subjectivities, for example, values, social experience, and viewpoint ( Allen, 2017 ). It is essential that a novice researcher learn to explicitly state a theoretical framework, because all research questions are being asked from the researcher’s implicit or explicit assumptions of a phenomenon of interest ( Schwandt, 2000 ).

Selecting Theoretical Frameworks

Theoretical frameworks are one of the most contemplated elements in our work in educational research. In this section, we share three important considerations for new scholars selecting a theoretical framework.

The first step in identifying a theoretical framework involves reflecting on the phenomenon within the study and the assumptions aligned with the phenomenon. The phenomenon involves the studied event. There are many possibilities, for example, student learning, instructional approach, or group organization. A researcher holds assumptions about how the phenomenon will be effected, influenced, changed, or portrayed. It is ultimately the researcher’s assumption(s) about the phenomenon that aligns with a theoretical framework. An example can help illustrate how a researcher’s reflection on the phenomenon and acknowledgment of assumptions can result in the identification of a theoretical framework.

In our example, a biology education researcher may be interested in exploring how students’ learning of difficult biological concepts can be supported by the interactions of group members. The phenomenon of interest is the interactions among the peers, and the researcher assumes that more knowledgeable students are important in supporting the learning of the group. As a result, the researcher may draw on Vygotsky’s (1978) sociocultural theory of learning and development that is focused on the phenomenon of student learning in a social setting. This theory posits the critical nature of interactions among students and between students and teachers in the process of building knowledge. A researcher drawing upon this framework holds the assumption that learning is a dynamic social process involving questions and explanations among students in the classroom and that more knowledgeable peers play an important part in the process of building conceptual knowledge.

It is important to state at this point that there are many different theoretical frameworks. Some frameworks focus on learning and knowing, while other theoretical frameworks focus on equity, empowerment, or discourse. Some frameworks are well articulated, and others are still being refined. For a new researcher, it can be challenging to find a theoretical framework. Two of the best ways to look for theoretical frameworks is through published works that highlight different frameworks.

When a theoretical framework is selected, it should clearly connect to all parts of the study. The framework should augment the study by adding a perspective that provides greater insights into the phenomenon. It should clearly align with the studies described in the literature review. For instance, a framework focused on learning would correspond to research that reported different learning outcomes for similar studies. The methods for data collection and analysis should also correspond to the framework. For instance, a study about instructional interventions could use a theoretical framework concerned with learning and could collect data about the effect of the intervention on what is learned. When the data are analyzed, the theoretical framework should provide added meaning to the findings, and the findings should align with the theoretical framework.

A study by Jensen and Lawson (2011) provides an example of how a theoretical framework connects different parts of the study. They compared undergraduate biology students in heterogeneous and homogeneous groups over the course of a semester. Jensen and Lawson (2011) assumed that learning involved collaboration and more knowledgeable peers, which made Vygotsky’s (1978) theory a good fit for their study. They predicted that students in heterogeneous groups would experience greater improvement in their reasoning abilities and science achievements with much of the learning guided by the more knowledgeable peers.

In the enactment of the study, they collected data about the instruction in traditional and inquiry-oriented classes, while the students worked in homogeneous or heterogeneous groups. To determine the effect of working in groups, the authors also measured students’ reasoning abilities and achievement. Each data-collection and analysis decision connected to understanding the influence of collaborative work.

Their findings highlighted aspects of Vygotsky’s (1978) theory of learning. One finding, for instance, posited that inquiry instruction, as a whole, resulted in reasoning and achievement gains. This links to Vygotsky (1978) , because inquiry instruction involves interactions among group members. A more nuanced finding was that group composition had a conditional effect. Heterogeneous groups performed better with more traditional and didactic instruction, regardless of the reasoning ability of the group members. Homogeneous groups worked better during interaction-rich activities for students with low reasoning ability. The authors attributed the variation to the different types of helping behaviors of students. High-performing students provided the answers, while students with low reasoning ability had to work collectively through the material. In terms of Vygotsky (1978) , this finding provided new insights into the learning context in which productive interactions can occur for students.

Another consideration in the selection and use of a theoretical framework pertains to its orientation to the study. This can result in the theoretical framework prioritizing individuals, institutions, and/or policies ( Anfara and Mertz, 2014 ). Frameworks that connect to individuals, for instance, could contribute to understanding their actions, learning, or knowledge. Institutional frameworks, on the other hand, offer insights into how institutions, organizations, or groups can influence individuals or materials. Policy theories provide ways to understand how national or local policies can dictate an emphasis on outcomes or instructional design. These different types of frameworks highlight different aspects in an educational setting, which influences the design of the study and the collection of data. In addition, these different frameworks offer a way to make sense of the data. Aligning the data collection and analysis with the framework ensures that a study is coherent and can contribute to the field.

New understandings emerge when different theoretical frameworks are used. For instance, Ebert-May et al. (2015) prioritized the individual level within conceptual change theory (see Posner et al. , 1982 ). In this theory, an individual’s knowledge changes when it no longer fits the phenomenon. Ebert-May et al. (2015) designed a professional development program challenging biology postdoctoral scholars’ existing conceptions of teaching. The authors reported that the biology postdoctoral scholars’ teaching practices became more student-centered as they were challenged to explain their instructional decision making. According to the theory, the biology postdoctoral scholars’ dissatisfaction in their descriptions of teaching and learning initiated change in their knowledge and instruction. These results reveal how conceptual change theory can explain the learning of participants and guide the design of professional development programming.

The communities of practice (CoP) theoretical framework ( Lave, 1988 ; Wenger, 1998 ) prioritizes the institutional level , suggesting that learning occurs when individuals learn from and contribute to the communities in which they reside. Grounded in the assumption of community learning, the literature on CoP suggests that, as individuals interact regularly with the other members of their group, they learn about the rules, roles, and goals of the community ( Allee, 2000 ). A study conducted by Gehrke and Kezar (2017) used the CoP framework to understand organizational change by examining the involvement of individual faculty engaged in a cross-institutional CoP focused on changing the instructional practice of faculty at each institution. In the CoP, faculty members were involved in enhancing instructional materials within their department, which aligned with an overarching goal of instituting instruction that embraced active learning. Not surprisingly, Gehrke and Kezar (2017) revealed that faculty who perceived the community culture as important in their work cultivated institutional change. Furthermore, they found that institutional change was sustained when key leaders served as mentors and provided support for faculty, and as faculty themselves developed into leaders. This study reveals the complexity of individual roles in a COP in order to support institutional instructional change.

It is important to explicitly state the theoretical framework used in a study, but elucidating a theoretical framework can be challenging for a new educational researcher. The literature review can help to identify an applicable theoretical framework. Focal areas of the review or central terms often connect to assumptions and assertions associated with the framework that pertain to the phenomenon of interest. Another way to identify a theoretical framework is self-reflection by the researcher on personal beliefs and understandings about the nature of knowledge the researcher brings to the study ( Lysaght, 2011 ). In stating one’s beliefs and understandings related to the study (e.g., students construct their knowledge, instructional materials support learning), an orientation becomes evident that will suggest a particular theoretical framework. Theoretical frameworks are not arbitrary , but purposefully selected.

With experience, a researcher may find expanded roles for theoretical frameworks. Researchers may revise an existing framework that has limited explanatory power, or they may decide there is a need to develop a new theoretical framework. These frameworks can emerge from a current study or the need to explain a phenomenon in a new way. Researchers may also find that multiple theoretical frameworks are necessary to frame and explore a problem, as different frameworks can provide different insights into a problem.

Finally, it is important to recognize that choosing “x” theoretical framework does not necessarily mean a researcher chooses “y” methodology and so on, nor is there a clear-cut, linear process in selecting a theoretical framework for one’s study. In part, the nonlinear process of identifying a theoretical framework is what makes understanding and using theoretical frameworks challenging. For the novice scholar, contemplating and understanding theoretical frameworks is essential. Fortunately, there are articles and books that can help:

• Creswell, J. W. (2018). Research design: Qualitative, quantitative, and mixed methods approaches (5th ed.). Los Angeles, CA: Sage. This book provides an overview of theoretical frameworks in general educational research.
• Ding, L. (2019). Theoretical perspectives of quantitative physics education research. Physical Review Physics Education Research , 15 (2), 020101-1–020101-13. This paper illustrates how a DBER field can use theoretical frameworks.
• Nehm, R. (2019). Biology education research: Building integrative frameworks for teaching and learning about living systems. Disciplinary and Interdisciplinary Science Education Research , 1 , ar15. https://doi.org/10.1186/s43031-019-0017-6 . This paper articulates the need for studies in BER to explicitly state theoretical frameworks and provides examples of potential studies.
• Patton, M. Q. (2015). Qualitative research & evaluation methods: Integrating theory and practice . Sage. This book also provides an overview of theoretical frameworks, but for both research and evaluation.

CONCEPTUAL FRAMEWORKS

Purpose of a conceptual framework.

A conceptual framework is a description of the way a researcher understands the factors and/or variables that are involved in the study and their relationships to one another. The purpose of a conceptual framework is to articulate the concepts under study using relevant literature ( Rocco and Plakhotnik, 2009 ) and to clarify the presumed relationships among those concepts ( Rocco and Plakhotnik, 2009 ; Anfara and Mertz, 2014 ). Conceptual frameworks are different from theoretical frameworks in both their breadth and grounding in established findings. Whereas a theoretical framework articulates the lens through which a researcher views the work, the conceptual framework is often more mechanistic and malleable.

Conceptual frameworks are broader, encompassing both established theories (i.e., theoretical frameworks) and the researchers’ own emergent ideas. Emergent ideas, for example, may be rooted in informal and/or unpublished observations from experience. These emergent ideas would not be considered a “theory” if they are not yet tested, supported by systematically collected evidence, and peer reviewed. However, they do still play an important role in the way researchers approach their studies. The conceptual framework allows authors to clearly describe their emergent ideas so that connections among ideas in the study and the significance of the study are apparent to readers.

Constructing Conceptual Frameworks

Including a conceptual framework in a research study is important, but researchers often opt to include either a conceptual or a theoretical framework. Either may be adequate, but both provide greater insight into the research approach. For instance, a research team plans to test a novel component of an existing theory. In their study, they describe the existing theoretical framework that informs their work and then present their own conceptual framework. Within this conceptual framework, specific topics portray emergent ideas that are related to the theory. Describing both frameworks allows readers to better understand the researchers’ assumptions, orientations, and understanding of concepts being investigated. For example, Connolly et al. (2018) included a conceptual framework that described how they applied a theoretical framework of social cognitive career theory (SCCT) to their study on teaching programs for doctoral students. In their conceptual framework, the authors described SCCT, explained how it applied to the investigation, and drew upon results from previous studies to justify the proposed connections between the theory and their emergent ideas.

In some cases, authors may be able to sufficiently describe their conceptualization of the phenomenon under study in an introduction alone, without a separate conceptual framework section. However, incomplete descriptions of how the researchers conceptualize the components of the study may limit the significance of the study by making the research less intelligible to readers. This is especially problematic when studying topics in which researchers use the same terms for different constructs or different terms for similar and overlapping constructs (e.g., inquiry, teacher beliefs, pedagogical content knowledge, or active learning). Authors must describe their conceptualization of a construct if the research is to be understandable and useful.

There are some key areas to consider regarding the inclusion of a conceptual framework in a study. To begin with, it is important to recognize that conceptual frameworks are constructed by the researchers conducting the study ( Rocco and Plakhotnik, 2009 ; Maxwell, 2012 ). This is different from theoretical frameworks that are often taken from established literature. Researchers should bring together ideas from the literature, but they may be influenced by their own experiences as a student and/or instructor, the shared experiences of others, or thought experiments as they construct a description, model, or representation of their understanding of the phenomenon under study. This is an exercise in intellectual organization and clarity that often considers what is learned, known, and experienced. The conceptual framework makes these constructs explicitly visible to readers, who may have different understandings of the phenomenon based on their prior knowledge and experience. There is no single method to go about this intellectual work.

Reeves et al. (2016) is an example of an article that proposed a conceptual framework about graduate teaching assistant professional development evaluation and research. The authors used existing literature to create a novel framework that filled a gap in current research and practice related to the training of graduate teaching assistants. This conceptual framework can guide the systematic collection of data by other researchers because the framework describes the relationships among various factors that influence teaching and learning. The Reeves et al. (2016) conceptual framework may be modified as additional data are collected and analyzed by other researchers. This is not uncommon, as conceptual frameworks can serve as catalysts for concerted research efforts that systematically explore a phenomenon (e.g., Reynolds et al. , 2012 ; Brownell and Kloser, 2015 ).

Sabel et al. (2017) used a conceptual framework in their exploration of how scaffolds, an external factor, interact with internal factors to support student learning. Their conceptual framework integrated principles from two theoretical frameworks, self-regulated learning and metacognition, to illustrate how the research team conceptualized students’ use of scaffolds in their learning ( Figure 1 ). Sabel et al. (2017) created this model using their interpretations of these two frameworks in the context of their teaching.

Conceptual framework from Sabel et al. (2017) .

A conceptual framework should describe the relationship among components of the investigation ( Anfara and Mertz, 2014 ). These relationships should guide the researcher’s methods of approaching the study ( Miles et al. , 2014 ) and inform both the data to be collected and how those data should be analyzed. Explicitly describing the connections among the ideas allows the researcher to justify the importance of the study and the rigor of the research design. Just as importantly, these frameworks help readers understand why certain components of a system were not explored in the study. This is a challenge in education research, which is rooted in complex environments with many variables that are difficult to control.

For example, Sabel et al. (2017) stated: “Scaffolds, such as enhanced answer keys and reflection questions, can help students and instructors bridge the external and internal factors and support learning” (p. 3). They connected the scaffolds in the study to the three dimensions of metacognition and the eventual transformation of existing ideas into new or revised ideas. Their framework provides a rationale for focusing on how students use two different scaffolds, and not on other factors that may influence a student’s success (self-efficacy, use of active learning, exam format, etc.).

In constructing conceptual frameworks, researchers should address needed areas of study and/or contradictions discovered in literature reviews. By attending to these areas, researchers can strengthen their arguments for the importance of a study. For instance, conceptual frameworks can address how the current study will fill gaps in the research, resolve contradictions in existing literature, or suggest a new area of study. While a literature review describes what is known and not known about the phenomenon, the conceptual framework leverages these gaps in describing the current study ( Maxwell, 2012 ). In the example of Sabel et al. (2017) , the authors indicated there was a gap in the literature regarding how scaffolds engage students in metacognition to promote learning in large classes. Their study helps fill that gap by describing how scaffolds can support students in the three dimensions of metacognition: intelligibility, plausibility, and wide applicability. In another example, Lane (2016) integrated research from science identity, the ethic of care, the sense of belonging, and an expertise model of student success to form a conceptual framework that addressed the critiques of other frameworks. In a more recent example, Sbeglia et al. (2021) illustrated how a conceptual framework influences the methodological choices and inferences in studies by educational researchers.

Sometimes researchers draw upon the conceptual frameworks of other researchers. When a researcher’s conceptual framework closely aligns with an existing framework, the discussion may be brief. For example, Ghee et al. (2016) referred to portions of SCCT as their conceptual framework to explain the significance of their work on students’ self-efficacy and career interests. Because the authors’ conceptualization of this phenomenon aligned with a previously described framework, they briefly mentioned the conceptual framework and provided additional citations that provided more detail for the readers.

Within both the BER and the broader DBER communities, conceptual frameworks have been used to describe different constructs. For example, some researchers have used the term “conceptual framework” to describe students’ conceptual understandings of a biological phenomenon. This is distinct from a researcher’s conceptual framework of the educational phenomenon under investigation, which may also need to be explicitly described in the article. Other studies have presented a research logic model or flowchart of the research design as a conceptual framework. These constructions can be quite valuable in helping readers understand the data-collection and analysis process. However, a model depicting the study design does not serve the same role as a conceptual framework. Researchers need to avoid conflating these constructs by differentiating the researchers’ conceptual framework that guides the study from the research design, when applicable.

Explicitly describing conceptual frameworks is essential in depicting the focus of the study. We have found that being explicit in a conceptual framework means using accepted terminology, referencing prior work, and clearly noting connections between terms. This description can also highlight gaps in the literature or suggest potential contributions to the field of study. A well-elucidated conceptual framework can suggest additional studies that may be warranted. This can also spur other researchers to consider how they would approach the examination of a phenomenon and could result in a revised conceptual framework.

It can be challenging to create conceptual frameworks, but they are important. Below are two resources that could be helpful in constructing and presenting conceptual frameworks in educational research:

• Maxwell, J. A. (2012). Qualitative research design: An interactive approach (3rd ed.). Los Angeles, CA: Sage. Chapter 3 in this book describes how to construct conceptual frameworks.
• Ravitch, S. M., & Riggan, M. (2016). Reason & rigor: How conceptual frameworks guide research . Los Angeles, CA: Sage. This book explains how conceptual frameworks guide the research questions, data collection, data analyses, and interpretation of results.

CONCLUDING THOUGHTS

Literature reviews, theoretical frameworks, and conceptual frameworks are all important in DBER and BER. Robust literature reviews reinforce the importance of a study. Theoretical frameworks connect the study to the base of knowledge in educational theory and specify the researcher’s assumptions. Conceptual frameworks allow researchers to explicitly describe their conceptualization of the relationships among the components of the phenomenon under study. Table 1 provides a general overview of these components in order to assist biology education researchers in thinking about these elements.

It is important to emphasize that these different elements are intertwined. When these elements are aligned and complement one another, the study is coherent, and the study findings contribute to knowledge in the field. When literature reviews, theoretical frameworks, and conceptual frameworks are disconnected from one another, the study suffers. The point of the study is lost, suggested findings are unsupported, or important conclusions are invisible to the researcher. In addition, this misalignment may be costly in terms of time and money.

Conducting a literature review, selecting a theoretical framework, and building a conceptual framework are some of the most difficult elements of a research study. It takes time to understand the relevant research, identify a theoretical framework that provides important insights into the study, and formulate a conceptual framework that organizes the finding. In the research process, there is often a constant back and forth among these elements as the study evolves. With an ongoing refinement of the review of literature, clarification of the theoretical framework, and articulation of a conceptual framework, a sound study can emerge that makes a contribution to the field. This is the goal of BER and education research.

Supplementary Material

• Allee, V. (2000). Knowledge networks and communities of learning . OD Practitioner , 32 ( 4 ), 4–13. [ Google Scholar ]
• Allen, M. (2017). The Sage encyclopedia of communication research methods (Vols. 1–4 ). Los Angeles, CA: Sage. 10.4135/9781483381411 [ CrossRef ] [ Google Scholar ]
• American Association for the Advancement of Science. (2011). Vision and change in undergraduate biology education: A call to action . Washington, DC. [ Google Scholar ]
• Anfara, V. A., Mertz, N. T. (2014). Setting the stage . In Anfara, V. A., Mertz, N. T. (eds.), Theoretical frameworks in qualitative research (pp. 1–22). Sage. [ Google Scholar ]
• Barnes, M. E., Brownell, S. E. (2016). Practices and perspectives of college instructors on addressing religious beliefs when teaching evolution . CBE—Life Sciences Education , 15 ( 2 ), ar18. https://doi.org/10.1187/cbe.15-11-0243 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Boote, D. N., Beile, P. (2005). Scholars before researchers: On the centrality of the dissertation literature review in research preparation . Educational Researcher , 34 ( 6 ), 3–15. 10.3102/0013189x034006003 [ CrossRef ] [ Google Scholar ]
• Booth, A., Sutton, A., Papaioannou, D. (2016a). Systemic approaches to a successful literature review (2nd ed.). Los Angeles, CA: Sage. [ Google Scholar ]
• Booth, W. C., Colomb, G. G., Williams, J. M., Bizup, J., Fitzgerald, W. T. (2016b). The craft of research (4th ed.). Chicago, IL: University of Chicago Press. [ Google Scholar ]
• Brownell, S. E., Kloser, M. J. (2015). Toward a conceptual framework for measuring the effectiveness of course-based undergraduate research experiences in undergraduate biology . Studies in Higher Education , 40 ( 3 ), 525–544. https://doi.org/10.1080/03075079.2015.1004234 [ Google Scholar ]
• Connolly, M. R., Lee, Y. G., Savoy, J. N. (2018). The effects of doctoral teaching development on early-career STEM scholars’ college teaching self-efficacy . CBE—Life Sciences Education , 17 ( 1 ), ar14. https://doi.org/10.1187/cbe.17-02-0039 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Cooper, K. M., Blattman, J. N., Hendrix, T., Brownell, S. E. (2019). The impact of broadly relevant novel discoveries on student project ownership in a traditional lab course turned CURE . CBE—Life Sciences Education , 18 ( 4 ), ar57. https://doi.org/10.1187/cbe.19-06-0113 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Creswell, J. W. (2018). Research design: Qualitative, quantitative, and mixed methods approaches (5th ed.). Los Angeles, CA: Sage. [ Google Scholar ]
• DeHaan, R. L. (2011). Education research in the biological sciences: A nine decade review (Paper commissioned by the NAS/NRC Committee on the Status, Contributions, and Future Directions of Discipline Based Education Research) . Washington, DC: National Academies Press. Retrieved May 20, 2022, from www7.nationalacademies.org/bose/DBER_Mee ting2_commissioned_papers_page.html [ Google Scholar ]
• Ding, L. (2019). Theoretical perspectives of quantitative physics education research . Physical Review Physics Education Research , 15 ( 2 ), 020101. [ Google Scholar ]
• Dirks, C. (2011). The current status and future direction of biology education research . Paper presented at: Second Committee Meeting on the Status, Contributions, and Future Directions of Discipline-Based Education Research, 18–19 October (Washington, DC). Retrieved May 20, 2022, from http://sites.nationalacademies.org/DBASSE/BOSE/DBASSE_071087 [ Google Scholar ]
• Duran, R. P., Eisenhart, M. A., Erickson, F. D., Grant, C. A., Green, J. L., Hedges, L. V., Schneider, B. L. (2006). Standards for reporting on empirical social science research in AERA publications: American Educational Research Association . Educational Researcher , 35 ( 6 ), 33–40. [ Google Scholar ]
• Ebert-May, D., Derting, T. L., Henkel, T. P., Middlemis Maher, J., Momsen, J. L., Arnold, B., Passmore, H. A. (2015). Breaking the cycle: Future faculty begin teaching with learner-centered strategies after professional development . CBE—Life Sciences Education , 14 ( 2 ), ar22. https://doi.org/10.1187/cbe.14-12-0222 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Galvan, J. L., Galvan, M. C. (2017). Writing literature reviews: A guide for students of the social and behavioral sciences (7th ed.). New York, NY: Routledge. https://doi.org/10.4324/9781315229386 [ Google Scholar ]
• Gehrke, S., Kezar, A. (2017). The roles of STEM faculty communities of practice in institutional and departmental reform in higher education . American Educational Research Journal , 54 ( 5 ), 803–833. https://doi.org/10.3102/0002831217706736 [ Google Scholar ]
• Ghee, M., Keels, M., Collins, D., Neal-Spence, C., Baker, E. (2016). Fine-tuning summer research programs to promote underrepresented students’ persistence in the STEM pathway . CBE—Life Sciences Education , 15 ( 3 ), ar28. https://doi.org/10.1187/cbe.16-01-0046 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Institute of Education Sciences & National Science Foundation. (2013). Common guidelines for education research and development . Retrieved May 20, 2022, from www.nsf.gov/pubs/2013/nsf13126/nsf13126.pdf
• Jensen, J. L., Lawson, A. (2011). Effects of collaborative group composition and inquiry instruction on reasoning gains and achievement in undergraduate biology . CBE—Life Sciences Education , 10 ( 1 ), 64–73. https://doi.org/10.1187/cbe.19-05-0098 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Kolpikova, E. P., Chen, D. C., Doherty, J. H. (2019). Does the format of preclass reading quizzes matter? An evaluation of traditional and gamified, adaptive preclass reading quizzes . CBE—Life Sciences Education , 18 ( 4 ), ar52. https://doi.org/10.1187/cbe.19-05-0098 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Labov, J. B., Reid, A. H., Yamamoto, K. R. (2010). Integrated biology and undergraduate science education: A new biology education for the twenty-first century? CBE—Life Sciences Education , 9 ( 1 ), 10–16. https://doi.org/10.1187/cbe.09-12-0092 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Lane, T. B. (2016). Beyond academic and social integration: Understanding the impact of a STEM enrichment program on the retention and degree attainment of underrepresented students . CBE—Life Sciences Education , 15 ( 3 ), ar39. https://doi.org/10.1187/cbe.16-01-0070 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Lave, J. (1988). Cognition in practice: Mind, mathematics and culture in everyday life . New York, NY: Cambridge University Press. [ Google Scholar ]
• Lo, S. M., Gardner, G. E., Reid, J., Napoleon-Fanis, V., Carroll, P., Smith, E., Sato, B. K. (2019). Prevailing questions and methodologies in biology education research: A longitudinal analysis of research in CBE — Life Sciences Education and at the Society for the Advancement of Biology Education Research . CBE—Life Sciences Education , 18 ( 1 ), ar9. https://doi.org/10.1187/cbe.18-08-0164 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Lysaght, Z. (2011). Epistemological and paradigmatic ecumenism in “Pasteur’s quadrant:” Tales from doctoral research . In Official Conference Proceedings of the Third Asian Conference on Education in Osaka, Japan . Retrieved May 20, 2022, from http://iafor.org/ace2011_offprint/ACE2011_offprint_0254.pdf
• Maxwell, J. A. (2012). Qualitative research design: An interactive approach (3rd ed.). Los Angeles, CA: Sage. [ Google Scholar ]
• Miles, M. B., Huberman, A. M., Saldaña, J. (2014). Qualitative data analysis (3rd ed.). Los Angeles, CA: Sage. [ Google Scholar ]
• Nehm, R. (2019). Biology education research: Building integrative frameworks for teaching and learning about living systems . Disciplinary and Interdisciplinary Science Education Research , 1 , ar15. https://doi.org/10.1186/s43031-019-0017-6 [ Google Scholar ]
• Patton, M. Q. (2015). Qualitative research & evaluation methods: Integrating theory and practice . Los Angeles, CA: Sage. [ Google Scholar ]
• Perry, J., Meir, E., Herron, J. C., Maruca, S., Stal, D. (2008). Evaluating two approaches to helping college students understand evolutionary trees through diagramming tasks . CBE—Life Sciences Education , 7 ( 2 ), 193–201. https://doi.org/10.1187/cbe.07-01-0007 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Posner, G. J., Strike, K. A., Hewson, P. W., Gertzog, W. A. (1982). Accommodation of a scientific conception: Toward a theory of conceptual change . Science Education , 66 ( 2 ), 211–227. [ Google Scholar ]
• Ravitch, S. M., Riggan, M. (2016). Reason & rigor: How conceptual frameworks guide research . Los Angeles, CA: Sage. [ Google Scholar ]
• Reeves, T. D., Marbach-Ad, G., Miller, K. R., Ridgway, J., Gardner, G. E., Schussler, E. E., Wischusen, E. W. (2016). A conceptual framework for graduate teaching assistant professional development evaluation and research . CBE—Life Sciences Education , 15 ( 2 ), es2. https://doi.org/10.1187/cbe.15-10-0225 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Reynolds, J. A., Thaiss, C., Katkin, W., Thompson, R. J. Jr. (2012). Writing-to-learn in undergraduate science education: A community-based, conceptually driven approach . CBE—Life Sciences Education , 11 ( 1 ), 17–25. https://doi.org/10.1187/cbe.11-08-0064 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Rocco, T. S., Plakhotnik, M. S. (2009). Literature reviews, conceptual frameworks, and theoretical frameworks: Terms, functions, and distinctions . Human Resource Development Review , 8 ( 1 ), 120–130. https://doi.org/10.1177/1534484309332617 [ Google Scholar ]
• Rodrigo-Peiris, T., Xiang, L., Cassone, V. M. (2018). A low-intensity, hybrid design between a “traditional” and a “course-based” research experience yields positive outcomes for science undergraduate freshmen and shows potential for large-scale application . CBE—Life Sciences Education , 17 ( 4 ), ar53. https://doi.org/10.1187/cbe.17-11-0248 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Sabel, J. L., Dauer, J. T., Forbes, C. T. (2017). Introductory biology students’ use of enhanced answer keys and reflection questions to engage in metacognition and enhance understanding . CBE—Life Sciences Education , 16 ( 3 ), ar40. https://doi.org/10.1187/cbe.16-10-0298 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Sbeglia, G. C., Goodridge, J. A., Gordon, L. H., Nehm, R. H. (2021). Are faculty changing? How reform frameworks, sampling intensities, and instrument measures impact inferences about student-centered teaching practices . CBE—Life Sciences Education , 20 ( 3 ), ar39. https://doi.org/10.1187/cbe.20-11-0259 [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Schwandt, T. A. (2000). Three epistemological stances for qualitative inquiry: Interpretivism, hermeneutics, and social constructionism . In Denzin, N. K., Lincoln, Y. S. (Eds.), Handbook of qualitative research (2nd ed., pp. 189–213). Los Angeles, CA: Sage. [ Google Scholar ]
• Sickel, A. J., Friedrichsen, P. (2013). Examining the evolution education literature with a focus on teachers: Major findings, goals for teacher preparation, and directions for future research . Evolution: Education and Outreach , 6 ( 1 ), 23. https://doi.org/10.1186/1936-6434-6-23 [ Google Scholar ]
• Singer, S. R., Nielsen, N. R., Schweingruber, H. A. (2012). Discipline-based education research: Understanding and improving learning in undergraduate science and engineering . Washington, DC: National Academies Press. [ Google Scholar ]
• Todd, A., Romine, W. L., Correa-Menendez, J. (2019). Modeling the transition from a phenotypic to genotypic conceptualization of genetics in a university-level introductory biology context . Research in Science Education , 49 ( 2 ), 569–589. https://doi.org/10.1007/s11165-017-9626-2 [ Google Scholar ]
• Vygotsky, L. S. (1978). Mind in society: The development of higher psychological processes . Cambridge, MA: Harvard University Press. [ Google Scholar ]
• Wenger, E. (1998). Communities of practice: Learning as a social system . Systems Thinker , 9 ( 5 ), 2–3. [ Google Scholar ]
• Ziadie, M. A., Andrews, T. C. (2018). Moving evolution education forward: A systematic analysis of literature to identify gaps in collective knowledge for teaching . CBE—Life Sciences Education , 17 ( 1 ), ar11. https://doi.org/10.1187/cbe.17-08-0190 [ PMC free article ] [ PubMed ] [ Google Scholar ]

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Comprehensive Literature Review

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Acknowledgements

Thank you to Jennifer Corbin for permission to use content from her research guide “Comprehensive Literature Review" ( http://libguides.tulane.edu/c.php?g=182708&p=1204573 ), Howard-TiltonLibrary, Tulane University.  And thank you to the University of Santa Cruz Library for permission to incorporate content from their guide "Write a Literature Review" ( http://guides.library.ucsc.edu/write-a-literature-review).

What Is a Literature Review?

A literature review is an overview of selected articles, books and other sources about a specific subject. The purpose is to summarize the existing research that has been done on the subject in order to put your research in context and to highlight what your research will add to the existing body of knowledge. Literature reviews are typically organized in some way (chronological, thematic, methodological).

Note that your literature review is separate from your works cited page or bibliography, although sources used in your literature review will need to be cited properly in them.

Let's take a look at an example of a literature review in an article, a dissertation, and a review article.

• Article Example: Abused Drugs in Insects Oliveira, J. S.; Baia, T. C.; Gama, R. A.; Lima, K. M. G. Development of a novel non-destructive method based on spectral fingerprint for determination of abused drug in insects: An alternative entomotoxicology approach. Microchemical Journal 2014, 115, 39-46.
• Dissertation Example: Forensic Entomotoxicology Peace, Michelle Renee'. "Forensic Entomotoxicology: A Study in the Deposition and Effects of Amphetamines and Barbiturates in the Larvae of the Black Blow Fly, Phormia Regina." Order No. 3177624 Virginia Commonwealth University, 2005. Ann Arbor: ProQuest. Web. 18 Aug. 2016.
• Review Article: Determination of Post-Burial Entomology Singh R, Sharma S, Sharma A. 2016. Determination of post-burial interval using entomology: A review. J Forensic Leg Med. 42:37-40.

Purpose of a Literature Review

A literature review may constitute an essential chapter of a thesis or dissertation, or may be a self-contained review of writings on a subject. In either case, its purpose is to:

• Place each work in the context of its contribution to the understanding of the subject under review
• Describe the relationship of each work to the others under consideration
• Identify new ways to interpret, and shed light on any gaps in, previous research
• Resolve conflicts amongst seemingly contradictory previous studies
• Identify areas of prior scholarship to prevent duplication of effort
• Point the way forward for further research
• Place one's original work (in the case of theses or dissertations) in the context of existing literature

The literature review itself, however, does not present new primary scholarship.

• Next: The Basic Steps >>
• Last Updated: Oct 4, 2023 12:50 PM
• URL: https://libguides.wvu.edu/LitReview

Write a Literature Review

1. narrow your topic and select papers accordingly, 2. search for literature, 3. read the selected articles thoroughly and evaluate them, 4. organize the selected papers by looking for patterns and by developing subtopics, 5. develop a thesis or purpose statement, 6. write the paper, 7. review your work.

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Consider your specific area of study. Think about what interests you and what interests other researchers in your field.

Talk to your professor, brainstorm, and read lecture notes and recent issues of periodicals in the field.

Limit your scope to a smaller topic area (ie. focusing on France's role in WWII instead of focusing on WWII in general).

• Four Steps to Narrow Your Research Topic (Video) This 3-minute video provides instructions on how to narrow the focus of your research topic.
• Developing a Research Question + Worksheet Use this worksheet to develop, assess, and refine your research questions. There is also a downloadable PDF version.

Define your source selection criteria (ie. articles published between a specific date range, focusing on a specific geographic region, or using a specific methodology).

Using keywords, search a library database.

Reference lists of recent articles and reviews can lead to other useful papers.

Include any studies contrary to your point of view.

Evaluate and synthesize the studies' findings and conclusions.

Note the following:

• Assumptions some or most researchers seem to make
• Methodologies, testing procedures, subjects, material tested researchers use
• Experts in the field: names/labs that are frequently referenced
• Conflicting theories, results, methodologies
• Popularity of theories and how this has/has not changed over time
• Findings that are common/contested
• Important trends in the research
• The most influential theories

Tip: If your literature review is extensive, find a large table surface, and on it place post-it notes or filing cards to organize all your findings into categories.

• Move them around if you decide that (a) they fit better under different headings, or (b) you need to establish new topic headings.
• Develop headings/subheadings that reflect the major themes and patterns you detected

Write a one or two sentence statement summarizing the conclusion you have reached about the major trends and developments you see in the research that has been conducted on your subject.

• Templates for Writing Thesis Statements This template provides a two-step guide for writing thesis statements. There is also a downloadable PDF version.
• 5 Types of Thesis Statements Learn about five different types of thesis statements to help you choose the best type for your research. There is also a downloadable PDF version.
• 5 Questions to Strengthen Your Thesis Statement Follow these five steps to strengthen your thesis statements. There is also a downloadable PDF version.

Follow the organizational structure you developed above, including the headings and subheadings you constructed.

Make certain that each section links logically to the one before and after.

Structure your sections by themes or subtopics, not by individual theorists or researchers.

• Tip: If you find that each paragraph begins with a researcher's name, it might indicate that, instead of evaluating and comparing the research literature from an analytical point of view, you have simply described what research has been done.

Prioritize analysis over description.

• For example, look at the following two passages and note that Student A merely describes the literature, whereas Student B takes a more analytical and evaluative approach by comparing and contrasting. You can also see that this evaluative approach is well signaled by linguistic markers indicating logical connections (words such as "however," "moreover") and phrases such as "substantiates the claim that," which indicate supporting evidence and Student B's ability to synthesize knowledge.

Student A: Smith (2000) concludes that personal privacy in their living quarters is the most important factor in nursing home residents' perception of their autonomy. He suggests that the physical environment in the more public spaces of the building did not have much impact on their perceptions. Neither the layout of the building nor the activities available seem to make much difference. Jones and Johnstone make the claim that the need to control one's environment is a fundamental need of life (2001), and suggest that the approach of most institutions, which is to provide total care, may be as bad as no care at all. If people have no choices or think that they have none, they become depressed.

Student B: After studying residents and staff from two intermediate care facilities in Calgary, Alberta, Smith (2000) came to the conclusion that except for the amount of personal privacy available to residents, the physical environment of these institutions had minimal if any effect on their perceptions of control (autonomy). However, French (1998) and Haroon (2000) found that availability of private areas is not the only aspect of the physical environment that determines residents' autonomy. Haroon interviewed 115 residents from 32 different nursing homes known to have different levels of autonomy (2000). It was found that physical structures, such as standardized furniture, heating that could not be individually regulated, and no possession of a house key for residents limited their feelings of independence. Moreover, Hope (2002), who interviewed 225 residents from various nursing homes, substantiates the claim that characteristics of the institutional environment such as the extent of resources in the facility, as well as its location, are features which residents have indicated as being of great importance to their independence.

• How to Integrate Critical Voice into Your Literature Review (Video)
• Look at the topic sentences of each paragraph. If you were to read only these sentences, would you find that your paper presented a clear position, logically developed, from beginning to end? The topic sentences of each paragraph should indicate the main points of your literature review.
• Make an outline of each section of the paper and decide whether you need to add information, to delete irrelevant information, or to re-structure sections.
• Read your work out loud. That way you will be better able to identify where you need punctuation marks to signal pauses or divisions within sentences, where you have made grammatical errors, or where your sentences are unclear.
• Since the purpose of a literature review is to demonstrate that the writer is familiar with the important professional literature on the chosen subject, check to make certain that you have covered all of the important, up-to-date, and pertinent texts. In the sciences and some of the social sciences it is important that your literature be quite recent; this is not so important in the humanities.
• Make certain that all of the citations and references are correct and that you are referencing in the appropriate style for your discipline. If you are uncertain which style to use, ask your professor.
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Social and Psychophysiological Consequences of the COVID-19 Pandemic: An Extensive Literature Review

Affiliations.

• 1 Faculty of Sports Sciences, Universidad Europea de Madrid, Madrid, Spain.
• 2 Grupo de Investigación en Cultura, Educación y Sociedad, Universidad de la Costa, Barranquilla, Colombia.
• 3 Studies Centre in Applied Combat, Toledo, Spain.
• 4 Laboratory of Evaluation of Human Biological Performance, School of Physical Education and Sport Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
• 5 Departamento de Educación, Universidad Antonio de Nebrija, Madrid, Spain.
• 6 Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, University of Valladolid, Soria, Spain.
• PMID: 33391099
• PMCID: PMC7772398
• DOI: 10.3389/fpsyg.2020.580225

The Coronavirus Disease 2019 (COVID-19) pandemic, now a global health crisis, has surprised health authorities around the world. Recent studies suggest that the measures taken to curb the spread of the COVID-19 outbreak have generated issues throughout the population. Thus, it is necessary to establish and identify the possible risk factors related to the psychosocial and psychophysiological strain during the COVID-19 outbreak. The present extensive literature review assesses the social, psychological, and physiological consequences of COVID-19, reviewing the impact of quarantine measures, isolation, vast human loss, social and financial consequences in the family's economies, and its impact on the psychological health of the population. We also discussed the effect of psychophysiological factors, considering the impact of physical inactivity and modifications in nutritional habits, at psychological and physiological levels. The present review includes an actualized to date bibliography, articles for which were methodologically analyzed to verify they met the standards of quality and scientific accuracy. Authors understand the pandemic as a multifactorial event for which only a profound and extensive analysis would lead to better compression and efficient intervention in the near future.

Keywords: COVID-19; anxiety; depression; gut; nutrition; pandemic; physical activity; stress.

Copyright © 2020 Clemente-Suárez, Dalamitros, Beltran-Velasco, Mielgo-Ayuso and Tornero-Aguilera.

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• Open access
• Published: 02 June 2024

Neuroleptic malignant syndrome and serotonin syndrome: a comparative bibliometric analysis

• Waleed M. Sweileh 1  

Orphanet Journal of Rare Diseases volume  19 , Article number:  221 ( 2024 ) Cite this article

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This study aimed to analyze and map scientific literature on Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS) from prestigious, internationally indexed journals. The objective was to identify key topics, impactful articles, prominent journals, research output, growth patterns, hotspots, and leading countries in the field, providing valuable insights for scholars, medical students, and international funding agencies.

A systematic search strategy was implemented in the PubMed MeSH database using specific keywords for NMS and SS. The search was conducted in the Scopus database, renowned for its extensive coverage of scholarly publications. Inclusion criteria comprised articles published from 1950 to December 31st, 2022, restricted to journal research and review articles written in English. Data were analyzed using Microsoft Excel for descriptive analysis, and VOSviewer was employed for bibliometric mapping.

The search yielded 1150 articles on NMS and 587 on SS, with the majority being case reports. Growth patterns revealed a surge in NMS research between 1981 and 1991, while SS research increased notably between 1993 and 1997. Active countries and journals differed between NMS and SS, with psychiatry journals predominating for NMS and pharmacology/toxicology journals for SS. Authorship analysis indicated higher multi-authored articles for NMS. Top impactful articles focused on review articles and pathogenic mechanisms. Research hotspots included antipsychotics and catatonia for NMS, while SS highlighted drug interactions and specific medications like linezolid and tramadol.

Conclusions

NMS and SS represent rare but life-threatening conditions, requiring detailed clinical and scientific understanding. Differential diagnosis and management necessitate caution in prescribing medications affecting central serotonin or dopamine systems, with awareness of potential drug interactions. International diagnostic tools and genetic screening tests may aid in safe diagnosis and prevention. Reporting rare cases and utilizing bibliometric analysis enhance knowledge dissemination and research exploration in the field of rare drug-induced medical conditions.

Introduction

Neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) are drug-induced, potentially life-threatening conditions that are infrequently encountered in medical practice, necessitating prompt intervention [ 1 , 2 , 3 , 4 ]. Neuroleptic Malignant Syndrome is characterized by a decrease in dopamine activity in the brain, often associated with the use of dopamine antagonists, primarily neuroleptic or antipsychotic medications [ 5 , 6 ]. While the exact pathophysiology of NMS remains incompletely understood, it is believed to involve dopamine dysregulation in the basal ganglia and hypothalamus. This dysregulation, particularly the blockade of dopamine receptors, especially D2 receptors, leads to a state of dopamine deficiency, manifesting in symptoms such as muscle rigidity, hyperthermia, and autonomic instability. Furthermore, withdrawal from dopamine agonists, such as L-Dopa, can also precipitate NMS in susceptible individuals. Serotonin Syndrome is characterized by an excess of serotonin (5-HT) in the central nervous system, typically stemming from the use of serotonergic medications or substances that elevate serotonin levels [ 7 , 8 ]. These drugs encompass antidepressants, notably selective serotonin reuptake inhibitors (SSRIs), opioids, specific psychedelics, serotonin agonists, and herbal supplements. The pathophysiology of SS revolves around the excessive stimulation of serotonin receptors, particularly the 5-HT2A receptors. This heightened stimulation precipitates a spectrum of symptoms, ranging from agitation, confusion, hyperthermia, muscle rigidity, to autonomic dysfunction. The severity of SS can vary widely, from mild manifestations to life-threatening conditions, contingent upon the extent of serotonin excess and individual susceptibility factors.

Both NMS and SS exhibit shared clinical manifestations, including hyperthermia, hypertension, hypersalivation, diaphoresis, and altered mental status [ 4 ], with instances of coexistence reported in some patients [ 9 ]. However, they diverge in their etiologies and clinical presentations. For instance, individuals with NMS typically display hyporeflexia, normal pupil size, and normal bowel sounds, contrasting with SS patients who often present with hyperreflexia, dilated pupils, and hyperactive bowel activity [ 10 ]. NMS is typified by lead-pipe muscle rigidity, whereas SS manifests with increased muscle tone, particularly in the lower extremities [ 11 , 12 ]. Given these distinctions, treatment strategies for NMS and SS diverge based on their underlying causes [ 2 ]. The mechanisms driving these syndromes differ significantly; while NMS involves diminished dopamine activity in the brain, SS is characterized by elevated serotonin levels [ 13 ]. Dopamine antagonists, such as neuroleptics or antipsychotics, are commonly implicated in NMS [ 14 , 15 , 16 ], although other triggers like withdrawal from dopamine agonists, like L-Dopa, can also induce NMS [ 17 , 18 ]. Conversely, SS can result from various drug classes, including antidepressants, opioids, psychedelics, serotonin agonists, and certain herbs [ 7 , 19 , 20 , 21 , 22 , 23 ]. Consequently, distinct medications are employed for their management; benzodiazepines and serotonin antagonists are standard therapy for SS, whereas dopaminergic agents and dantrolene are preferred for NMS [ 10 ]. While the incidence of NMS remains low, particularly among patients receiving newer generation antipsychotics [ 24 , 25 ], recent studies on SS incidence are lacking. However, a 1999 study reported an incidence of 0.4 cases per 1000 patient-months with nefazodone [ 26 ], while SS incidence reaches 14–16% in cases of selective serotonin reuptake inhibitor (SSRI) overdose [ 27 ].

Research context and objectives

The landscape of psychiatric pharmacotherapy has evolved over time, witnessing a surge in the number of approved drugs and the introduction of novel classes into clinical practice [ 28 , 29 , 30 , 31 ]. This trend is particularly notable in the treatment of depression and schizophrenia, where the absence of universally safe and effective drugs persists [ 32 , 33 , 34 , 35 , 36 ]. Additionally, off-label utilization of antidepressants and antipsychotics has been observed among patients with dementia and other neuro-cognitive disorders [ 37 , 38 , 39 , 40 , 41 ], contributing to an upward trajectory in psychiatric drug consumption [ 42 , 43 ]. The risk of SS is linked to any medication or herb augmenting the central serotonergic pathway, necessitating vigilant monitoring by healthcare professionals due to the potential for adverse effects, whether as a primary mechanism or side effect [ 20 ]. A concerning trend of unsupported polypharmacy in psychiatric medications has also emerged [ 44 ], along with significant prescribing of antidepressants and antipsychotics to dementia patients without documented indications of depression or psychosis [ 45 , 46 ], mirroring similar trends among individuals with intellectual disabilities [ 47 ]. The escalating demand for psychiatric therapy raises apprehensions regarding the likelihood of adverse medication effects [ 48 ], exacerbated by increased prescribing rates, polypharmacy, and off-label usage, which heighten the incidence of drug-induced toxicities, including NMS and SS. Analyzing published literature on drug-induced NMS and SS provides valuable insights into these rare yet severe toxicities, aligning with the pressing global public health burden of depression, schizophrenia, and related conditions, accentuated by the fatal toxicities associated with specific psychiatric medications. This scientific literature on NMS and SS is ripe for analysis and mapping to delineate current research hotspots [ 49 , 50 , 51 , 52 , 53 , 54 , 55 ], addressing the gap in the literature. Accordingly, the present study aims to analyze and map scientific research on NMS and SS published in prestigious, internationally indexed journals. Through this analysis, the study seeks to identify key topics, impactful articles, prominent journals, research output, growth patterns, hotspots, and leading countries in the field, providing valuable insights for scholars, medical students, and international funding agencies to discern research trajectories, bibliographic trends, and knowledge structures pertaining to NMS and SS. Ultimately, this endeavor aims to invigorate scholarly discourse and inform clinical practice in the field.

Database and keywords

In this study, we employed a systematic search strategy to extract relevant scientific literature on NMS and SS from the PubMed MeSH database. Specifically, we utilized the following keywords:

Malignant neuroleptic syndrome: “malignant neuroleptic syndrome”.

Serotonin syndrome: “serotonin syndrome” or “serotonin toxicity”.

To ensure comprehensive coverage, we conducted our search in Scopus, a prestigious scientific database owned by Elsevier, which has previously been utilized for analyzing research in psychiatry [ 56 , 57 ]. Scopus is renowned for its extensive coverage, encompassing a vast array of scholarly publications in the field. Notably, Scopus encompasses over 95% of the content included in other databases such as PubMed and Web of Science, rendering it an ideal platform for our study [ 58 ].

Inclusion and exclusion criteria

We restricted our search to articles published from 1950 to December 31st, 2022, and focused exclusively on journal research and review articles written in English. Excluded from our analysis were editorials, notes, letters, and conference abstracts. Additionally, articles pertaining to non-human subjects were excluded, ensuring the relevance of our findings. We meticulously reviewed the titles and abstracts of over 100 articles to eliminate irrelevant publications, such as those mentioning NMS or SS only marginally, thereby refining the scope of our analysis.

Our search strategy yielded results indicative of its validity, as evidenced by the prominent presence of leading scientists and journals in the fields of psychiatry and pharmacology. This reaffirmed the robustness of our search criteria and the relevance of the retrieved literature to our study objectives.

Data management, analysis, and mapping

The dataset comprising the retrieved articles was subjected to descriptive analysis using Microsoft Excel. Subsequently, we employed VOSviewer, a freely available online tool, for bibliometric mapping purposes [ 59 ]. VOSviewer maps offer researchers a visual tool for exploring bibliometric data, revealing patterns, relationships, and trends within a dataset. Interpretation of these maps involves understanding several key elements. Firstly, node size indicates the prominence or frequency of an item, with larger nodes representing more significant themes or influential publications. Secondly, node color categorizes items into clusters, with similar colors indicating thematic groupings. Thirdly, the thickness of connecting lines between nodes signifies the strength of associations, with thicker lines indicating stronger connections. Lastly, the distance between nodes reflects the similarity or dissimilarity between items, with closer nodes indicating stronger relationships. Overall, VOSviewer maps provide a comprehensive visual overview of bibliometric data, enabling researchers to identify clusters, influential publications, and emerging trends within their field of study by considering the interplay between node size, color, line thickness, and spatial relationships. Within the descriptive analysis, we presented lists of active countries and journals, alongside a linear graph illustrating the growth of publications over time. In the keyword visualization map generated using VOSviewer, node size corresponded to the frequency of occurrence of each keyword, enabling visual identification of prominent themes. Similarly, in the journal visualization map, node size reflected the normalized citation count received by each journal, providing insights into publication impact within the field.

Number of publications

The search strategy yielded a total of 1150 articles on NMS and 587 on SS. Among the articles on NMS, 791 (68.8%) were case reports, while 384 (65.4%) of the articles on SS took the form of case reports.

Growth of publications

The earliest scientific publication on NMS dates back to 1973 [ 60 ], while publications on SS emerged in 1979 [ 61 ]. Research on NMS experienced a notable surge between 1981 and 1991, followed by a fluctuating decline. Conversely, research on SS saw a steep increase between 1993 and 1997, followed by a fluctuating rise. Figure  1 illustrates the growth trends of research on NMS and SS.

Annual growth of publications of NMS (blue line) and SS (green line). The Figure was created by SPSS program

Active countries and journals

Table  1 outlines the top five countries contributing articles on NMS and SS. Japan ranked second in NMS publications but fifth in SS publications. Table  2 presents the top five active journals for both NMS and SS, with NMS publications primarily within psychiatry journals and SS publications within pharmacology/toxicology journals.

Authorship analysis

Articles on NMS involved 3820 authors (mean = 3.1 authors per article), with 89 (7.3%) single-authored and 171 (14.1%) multi-authored articles. Similarly, articles on SS included 2105 authors (mean = 3.0 authors per article), with 102 (16.0%) single-authored and 41 (7.1%) multi-authored articles.

Most impactful articles

The top five impactful articles on NMS comprised mainly review articles and a research article focusing on the pathogenic role of dopamine antagonists [ 62 ]. For SS, the top five impactful articles included review articles and research articles discussing the Hunter diagnostic criteria [ 63 ] and the role of monoamine oxidase inhibitors (MAO-I) and opioid analgesics in serotonin toxicity [ 64 ].

Research hotspots

Research hotspots were identified by mapping author keywords with a minimum occurrence of five times (Figs.  2 and 3 ). Notable hotspots for SS included antidepressants, SSRIs, tramadol, linezolid, cyproheptadine, and drug interactions. For NMS, hotspots included antipsychotics (various drug names), catatonia, and rhabdomyolysis.

Network visualization map of author keywords with minimum occurrences of five times. Large nodes represent research hotspots on NMS. The term NMS was not shown to make other keywords more visible

Network visualization map of author keywords with minimum occurrences of five times. Large nodes represent research hotspots on SS. The term SS was not shown to make other keywords more visible

Journal citation analysis

The top 15 active journals in publishing articles on NMS and SS were mapped (Figs.  4 and 5 ). Notably, articles on NMS published in the American Journal of Psychiatry and the Journal of Clinical Psychiatry received the highest number of citations per article. Similarly, articles on SS published in Clinical Toxicology and the Annals of Pharmacotherapy garnered the most citations per article.

Network visualization map of the top 15 journals in the field of NMS. Large node sized indicates higher normalized citation count

Network visualization map of the top 15 journals in the field of SS. Large node sized indicates higher normalized citation count

Geographic mapping

The geographic distribution of research publications on NMS and SS was illustrated on a worldwide map (Fig.  6 ), with the majority of contributions originating from the US. Several countries in specific regions showed minimal to no research output on either NMS or SS.

Worldwide distribution of research publications on NMS and SS. Figure was created by Microsoft Excel

Molecular genetics

The retrieved literature on NMS has 20 articles that discussed the potential link between NMS and certain genetics. Ten articles discussed the potential linkage between Cytochrome 2D6 and potential risk for NMS [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. Five articles discussed the potential linkage between dopamine receptor 2 gene polymorphism and NMS [ 75 , 76 , 77 , 78 , 79 ]. Four articles discussed the linkage between ryanodine receptor gene mutations and susceptibility to NMS [ 80 , 81 , 82 , 83 ]. No association was found between NMS and serotonin receptor gene variation [ 84 ]. The literature on SS has few articles that discussed the genetic predisposition of patients to SS such as the 5-HT receptor gene or the CYP 2D6 gene polymorphism [ 85 , 86 ].

Drug interactions

Serious drug-drug interactions leading to NMS were mentioned in a limited number of articles and involved the administration of two dopamine antagonists [ 87 ] or two atypical antipsychotic drugs [ 88 ]. However, there were many articles discussing potential SS caused by drug-drug interactions, which included SSRI–methylene blue [ 89 ], SSRI–metoclopramide [ 89 ], sertraline–phenelzine [ 90 ], anti-depressants–opioids [ 91 ], citalopram-fentanyl [ 92 ], a combination of two anti-depressants [ 93 ], SSRI-linezolid [ 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ], sertraline–phenelzine [ 90 ], citalopram-buspirone [ 103 ], venlafaxine-tranylcypromine [ 104 ], and many others [ 92 , 105 , 106 , 107 , 108 , 109 ].

Non-psychiatric causative agents

The retrieved literature on SS, showed that several drugs and drug classes not related to antidepressants can induce SS. Examples of such drugs included Linezolid, CNS stimulants (amphetamine), hallucinogens (LSD), opioids (fentanyl), ondansetron, sumatriptan, and certain herbs (St. John’s wort), metoclopramide, ritonavir, and others [ 5 , 20 , 110 , 111 ]. The retrieved literature on NMS showed that drug-induced NMS is limited to antipsychotics and withdrawal of dopamine agonists [ 112 , 113 , 114 ].

Diagnostic criteria

For NMS, there were 30 articles that discussed issues related to diagnosis. In 2011, an international panel tried to develop NMS diagnostic criteria [ 115 , 116 ]. The neutrophil-lymphocyte ratio was suggested by certain researchers as a diagnostic test for NMS [ 117 , 118 ]. The differential diagnosis for NMS compared to SS and catatonia was also published [ 13 , 118 , 119 ]. For SS, there were 17 articles that discussed issues related to diagnosis of SS. The Hunter diagnostic criteria was one of these articles [ 63 ]. Other articles discussed controversies and the importance of differential diagnosis in SS [ 120 ].

The current study analyzed and compared the scientific literature on two rare drug-induced conditions with certain overlapping clinical features. Both syndromes are mainly caused by medications used in psychiatry, such as those for schizophrenia and depression. The name “NMS” implies that the syndrome is correlated with the use of neuroleptic medications, while the name “SS” implies that it is correlated with any medication or herb that raises serotonin centrally.

The analysis showed that the volume of research publications on NMS was larger and started earlier than research publications on SS. The NMS is associated with the use of dopamine antagonists (neuroleptics). The history of using old-generation antipsychotics for the treatment of schizophrenia dates back to the 1950s [ 121 , 122 , 123 , 124 , 125 ]. On the other hand, the introduction of the SSRI drug class, the main causative agent of SS, dates back to the late 1980s [ 126 ]. The difference in the history of introduction into clinical practice explains the differences between SS and NMS in growth patterns. The difference in the volume of literature between the two syndromes could be due to diagnostic uncertainty [ 127 ] for NMS versus SS, the seriousness of medical complications, or debate regarding whether an atypical antipsychotic drug class causes NMS in a similar way to conventional antipsychotics [ 13 , 30 , 128 , 129 , 130 ]. The current study showed that the number of research publications on NMS started to decline after 1991 but the number of publications on SS started to increase after 1997. The introduction of atypical antipsychotics with lesser dopaminergic side effects than conventional antipsychotics decreased the incidence of NMS and therefore decreased the number of publications with time. On the other hand, the increased number of SS publications after 1997 could be explained by the many reported drug interactions at serotonin level leading to more cases of SS with time.

The current study showed that journals in the field of psychiatry ranked highest in publishing articles on NMS, while those in the field of pharmacology/toxicology ranked highest in publishing articles on SS. The reason for this difference is difficult to explain. However, NMS is primarily limited to schizophrenia patients taking antipsychotic drugs, while SS might occur in normal people taking SSRIs for depression or any other condition. Furthermore, the potentially large numbers of drug- or drug-herb interactions make the SS interesting to pharmacology/toxicology journals [ 22 ]. Actually, SS has been termed “serotonin toxicity” implying relatedness to toxicology [ 131 ].

The findings of the current study regarding active countries were not surprising. The English-speaking countries, the US, the UK, Australia, and Canada showed leading roles in many scientific disciplines and ranked first in several studies that analyzed research activity [ 132 , 133 , 134 , 135 ]. This is due to advancements in technology, medicine, clinical practice, and research funding in high-income countries relative to other countries. However, there are also reasons related to the nature of journals indexed in Scopus. The vast majority of Scopus-indexed journals publish articles in English, and the vast majority of the journals are issued by publishers and institutions based in the US, Europe, or Australia. Therefore, Scopus might be biased toward scholars in English-speaking countries. The finding that research articles on NMS tend to be multi-authored while those on SS are not is not easy to explain. However, it is possible that cases of NMS tend to involve a larger medical team due to the nature of complications that might involve renal and blood complications. Furthermore, the treatment of NMS requires medications and follow-up. All this makes the number of authors in a case study of NMS higher than those involved in SS cases [ 13 , 136 , 137 ].

Of the retrieved articles on SS and NMS, the research article “The hunter serotonin toxicity criteria: Simple and accurate diagnostic decision rules for serotonin toxicity” [ 63 ] received the highest number of citations excluding the review articles. The diagnosis of SS is based on the clinical symptoms and the medical history of the patient. Harvey Sternbach introduced the first diagnostic criteria for SS in 1991 and the Hunter Diagnostic Criteria tool was introduced in 2003 [ 63 , 138 ].

Mapping the retrieved literature on NMS showed that rhabdomyolysis and catatonia constituted distinct research hotspots in addition to those related to antipsychotic medications and schizophrenia. However, mapping the author keywords of SS research publications showed that linezolid, drug interactions, and tramadol constituted research hotspots in addition to antidepressants and SSRIs. Rhabdomyolysis has been reported as a consequence of NMS even among children and adolescents [ 139 , 140 ]. However, reports of rhabdomyolysis among patients taking antipsychotics were published, suggesting that rhabdomyolysis could be a side effect of antipsychotics even in the absence of NMS [ 139 , 140 ]. Catatonia is, as NMS, a consequence of neuroleptic drugs, and there is an overlap in clinical features between the symptoms of catatonia and those of NMS, which makes the distinction between them difficult [ 141 ]. Linezolid is an antibiotic that was originally designed to be used as an anti-depressant by virtue of its MAO enzyme inhibition property [ 142 ]. This explains the many cases of SS induced by drug interactions with Linezolid [ 141 ]. The relatively higher number of research articles on drug/herb interactions leading to SS is attributed to the presence of many and different drug classes that affect and increase serotonergic pathways in the brain [ 90 , 105 , 109 , 143 ]. The scientific controversy about the potential ability of tramadol to cause SS received a high number of citations. Current scientific evidence supports the ability of tramadol to cause SS due to its molecular pharmacological effects on both the opioid and serotonergic systems [ 105 , 107 , 144 , 145 , 146 , 147 ]. Cyproheptadine was also a research hotspot in the field of SS. Cyproheptadine has anti-histaminic, anticholinergic, and anti-serotonergic properties and that is why it has been used to counter the symptoms of SS [ 148 , 149 , 150 ].

The current study showed that SS has a wide range of possible drug/herb interactions due to the many drugs that affect the serotonin system. Of particular interest is the one with opioid analgesics, since they are commonly used in hospital settings. Opioids, including fentanyl and even dextromethorphan in cough syrups, were reported to increase serotonin levels, and therefore caution should be practiced when given to patients with SSRIs in their medical records [ 19 , 22 , 109 , 151 ].

Limitations

Limitations arise in this study from various factors. Firstly, the reliance on the Scopus database for literature retrieval could potentially limit the inclusivity of articles from low- and middle-income countries. Although Scopus offers extensive coverage, the possibility exists that some relevant journals from these regions may not be indexed, thereby leading to a potential underestimation of publications from certain geographic areas. Secondly, despite efforts to employ a comprehensive search strategy, the use of a title-abstract search method might have resulted in the retrieval of some false-positive results. While validation tests were conducted to mitigate this issue, the possibility of false positives cannot be entirely ruled out. Thirdly, the analysis focused solely on articles published in English-language journals, which could introduce a language bias and limit the generalizability of findings. This exclusion of literature published in other languages may have led to the omission of relevant data from non-English sources. Lastly, diagnostic uncertainty poses a challenge in distinguishing between neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) due to overlapping clinical features and the absence of definitive diagnostic tests. Misdiagnosis or underreporting of cases may have occurred, potentially impacting the accuracy of the literature analysis and conclusions drawn from it.

In conclusion, NMS and SS represent rare but potentially life-threatening conditions associated with drug-induced dysregulation of dopamine and serotonin systems, respectively. The study analyzed and compared the scientific literature on these syndromes, revealing distinct growth patterns, research hotspots, and publication trends. The findings underscored the evolving landscape of psychiatric pharmacotherapy and the complexities involved in diagnosing and managing NMS and SS. While NMS research exhibited a longer history and a decline in publications over time, SS research witnessed a notable increase in publications, reflecting advancements in pharmacological understanding and the recognition of SS as a significant clinical entity. Identified research hotspots provided valuable insights into emerging areas of interest, including drug interactions, molecular genetics, and diagnostic criteria. Understanding these trends is essential for informing clinical practice, guiding future research endeavors, and promoting collaboration among scholars and healthcare professionals. Despite the study’s contributions, several limitations warrant consideration, including database restrictions, potential publication bias, and diagnostic uncertainties. Addressing these limitations through expanded literature search strategies, international collaboration, and improved diagnostic tools is crucial for advancing knowledge and enhancing patient care in the field of rare drug-induced syndromes. Moving forward, efforts to develop standardized diagnostic criteria, genetic screening tools, and international reporting mechanisms for NMS and SS are warranted. Additionally, continued bibliometric analysis and mapping of literature on rare medical conditions can facilitate ongoing research and contribute to the dissemination of knowledge across global healthcare communities.

Data availability

All data present in this article can be retrieved from Scopus using keywords listed in the methodology.

Abbreviations

• Neuroleptic malignant syndrome

Serotonin Syndrome/ Serotonin toxicity

Darracq MA, Comment. Neuroleptic malignant syndrome versus serotonin syndrome: the search for a diagnostic tool. Ann Pharmacother. 2012;46(4):611–2. https://doi.org/10.1345/aph.1P787a . author reply 3.

Article   PubMed   Google Scholar  

Sokoro AA, Zivot J, Ariano RE. Neuroleptic malignant syndrome versus serotonin syndrome: the search for a diagnostic tool. Ann Pharmacother. 2011;45(9):e50. https://doi.org/10.1345/aph.1P787 .

Fernández M, Lago L, Alonso MG, Guede A, Benavente JL, Olivares JM. Serotonin syndrome versus neuroleptic malignant syndrome: a case report. Actas Esp Psiquiatr. 2018;46(2):68–74.

PubMed   Google Scholar  

Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep. 2014. https://doi.org/10.1136/bcr-2014-204154 . 2014.

Article   PubMed   PubMed Central   Google Scholar  

Tormoehlen LM, Rusyniak DE. Neuroleptic malignant syndrome and serotonin syndrome. Handb Clin Neurol. 2018;157:663–75. https://doi.org/10.1016/b978-0-444-64074-1.00039-2 .

Ware MR, Feller DB, Hall KL. Neuroleptic malignant syndrome: diagnosis and management. Prim Care Companion CNS Disord. 2018;20(1). https://doi.org/10.4088/PCC.17r02185 .

Maitland S, Baker M. Serotonin syndrome. Drug Ther Bull. 2022;60(6):88–91. https://doi.org/10.1136/dtb.2021.000032 .

Mikkelsen N, Damkier P, Pedersen SA. Serotonin syndrome-A focused review. Basic Clin Pharmacol Toxicol. 2023;133(2):124–9. https://doi.org/10.1111/bcpt.13912 .

Article   CAS   PubMed   Google Scholar  

Prakash S, Lodha D, Rawat KS. Coexistence of serotonin syndrome and neuroleptic malignant syndrome: does it exist? BMJ Case Rep. 2021;14(8). https://doi.org/10.1136/bcr-2021-241578 .

Katus LE, Frucht SJ. Management of Serotonin Syndrome and neuroleptic malignant syndrome. Curr Treat Options Neurol. 2016;18(9):39. https://doi.org/10.1007/s11940-016-0423-4 .

Hadad E, Weinbroum AA, Ben-Abraham R. Drug-induced hyperthermia and muscle rigidity: a practical approach. Eur J Emerg Med. 2003;10(2):149–54. https://doi.org/10.1097/00063110-200306000-00018 .

Haddad PM, Dursun SM. Neurological complications of psychiatric drugs: clinical features and management. Hum Psychopharmacol. 2008;23(Suppl 1):15–26. https://doi.org/10.1002/hup.918 .

Perry PJ, Wilborn CA. Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management. Ann Clin Psychiatry. 2012;24(2):155–62.

Pileggi DJ, Cook AM. Neuroleptic malignant syndrome. Ann Pharmacother. 2016;50(11):973–81. https://doi.org/10.1177/1060028016657553 .

Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry. 1998;155(8):1113–6. https://doi.org/10.1176/ajp.155.8.1113 .

Belvederi Murri M, Guaglianone A, Bugliani M, Calcagno P, Respino M, Serafini G, et al. Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D. 2015;15(1):45–62. https://doi.org/10.1007/s40268-014-0078-0 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Mizuno Y, Takubo H, Mizuta E, Kuno S. Malignant syndrome in Parkinson’s disease: concept and review of the literature. Parkinsonism Relat Disord. 2003;9(Suppl 1). https://doi.org/10.1016/s1353-8020(02)00125-6 . :S3-9.

Rainer C, Scheinost NA, Lefeber EJ. Neuroleptic malignant syndrome. When levodopa withdrawal is the cause. Postgrad Med. 1991;89(5):175–8. https://doi.org/10.1080/00325481.1991.11700900 .

Baldo BA, Rose MA. The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review. Br J Anaesth. 2020;124(1):44–62. https://doi.org/10.1016/j.bja.2019.08.010 .

Bartlett D. Drug-Induced Serotonin Syndrome. Crit Care Nurse. 2017;37(1):49–54. https://doi.org/10.4037/ccn2017169 .

Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, et al. Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239–82. https://doi.org/10.2165/00003495-200565090-00005 .

Baldo BA. Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects. Arch Toxicol. 2018;92(8):2457–73. https://doi.org/10.1007/s00204-018-2244-6 .

Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res. 2019;12:1178646919873925. https://doi.org/10.1177/1178646919873925 .

Velamoor VR. Neuroleptic malignant syndrome. Recognition, prevention and management. Drug Saf. 1998;19(1):73–82. https://doi.org/10.2165/00002018-199819010-00006 .

Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41–7. https://doi.org/10.1177/1941875210386491 .

Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49(448):871–4.

CAS   PubMed   PubMed Central   Google Scholar  

Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004;42(3):277–85. https://doi.org/10.1081/clt-120037428 .

Adell A. Brain NMDA receptors in Schizophrenia and Depression. Biomolecules. 2020;10(6). https://doi.org/10.3390/biom10060947 .

Laszlovszky I, Barabássy Á, Németh G, Cariprazine. A broad-spectrum antipsychotic for the treatment of Schizophrenia: Pharmacology, Efficacy, and Safety. Adv Ther. 2021;38(7):3652–73. https://doi.org/10.1007/s12325-021-01797-5 .

Orzelska-Górka J, Mikulska J, Wiszniewska A, Biała G. New atypical antipsychotics in the treatment of Schizophrenia and Depression. Int J Mol Sci. 2022;23(18). https://doi.org/10.3390/ijms231810624 .

Marwaha S, Palmer E, Suppes T, Cons E, Young AH, Upthegrove R. Novel and emerging treatments for major depression. Lancet. 2023;401(10371):141–53. https://doi.org/10.1016/s0140-6736(22)02080-3 .

Preda A, Shapiro BB. A safety evaluation of aripiprazole in the treatment of schizophrenia. Expert Opin Drug Saf. 2020;19(12):1529–38. https://doi.org/10.1080/14740338.2020.1832990 .

Solmi M, Murru A, Pacchiarotti I, Undurraga J, Veronese N, Fornaro M, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757–77. https://doi.org/10.2147/tcrm.S117321 .

Cheniaux E, Nardi AE. Evaluating the efficacy and safety of antidepressants in patients with bipolar disorder. Expert Opin Drug Saf. 2019;18(10):893–913. https://doi.org/10.1080/14740338.2019.1651291 .

Sommer BR, Fenn H, Pompei P, DeBattista C, Lembke A, Wang P, et al. Safety of antidepressants in the elderly. Expert Opin Drug Saf. 2003;2(4):367–83. https://doi.org/10.1517/14740338.2.4.367 .

Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA. The Safety, Tolerability and Risks Associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom. 2016;85(5):270–88. https://doi.org/10.1159/000447034 .

Yunusa I, Rashid N, Demos GN, Mahadik BS, Abler VC, Rajagopalan K. Comparative outcomes of commonly used off-label atypical antipsychotics in the treatment of dementia-related psychosis: a Network Meta-analysis. Adv Ther. 2022;39(5):1993–2008. https://doi.org/10.1007/s12325-022-02075-8 .

Scheltema Beduin A, de Haan L. Off-label second generation antipsychotics for impulse regulation disorders: a review. Psychopharmacol Bull. 2010;43(3):45–81.

Hefner G, Wolff J, Toto S, Reißner P, Klimke A. Off-label use of antidepressants, antipsychotics, and mood-stabilizers in psychiatry. J Neural Transm (Vienna). 2022;129(11):1353–65. https://doi.org/10.1007/s00702-022-02542-0 .

Haw C, Stubbs J. Off-label use of antipsychotics: are we mad? Expert Opin Drug Saf. 2007;6(5):533–45. https://doi.org/10.1517/14740338.6.5.533 .

Maher AR, Theodore G. Summary of the comparative effectiveness review on off-label use of atypical antipsychotics. J Manag Care Pharm. 2012;18(5 Suppl B):S1–20. https://doi.org/10.18553/jmcp.2012.18.s5-b.1 .

González-López MDC, Díaz-Calvo V, Ruíz-González C, Nievas-Soriano BJ, Rebollo-Lavado B, Parrón-Carreño T. Consumption of Psychiatric drugs in Primary Care during the COVID-19 pandemic. Int J Environ Res Public Health. 2022;19(8). https://doi.org/10.3390/ijerph19084782 .

Heald AH, Stedman M, Farman S, Khine C, Davies M, De Hert M, et al. Links between the amount of antipsychotic medication prescribed per population at general practice level, local demographic factors and medication selection. BMC Psychiatry. 2020;20(1):528. https://doi.org/10.1186/s12888-020-02915-3 .

Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry. 2010;67(1):26–36. https://doi.org/10.1001/archgenpsychiatry.2009.175 .

Drummond N, McCleary L, Freiheit E, Molnar F, Dalziel W, Cohen C, et al. Antidepressant and antipsychotic prescribing in primary care for people with dementia. Can Fam Physician. 2018;64(11):e488–97.

PubMed   PubMed Central   Google Scholar  

Luo H, Lau WCY, Chai Y, Torre CO, Howard R, Liu KY, et al. Rates of antipsychotic drug prescribing among people living with Dementia during the COVID-19 pandemic. JAMA Psychiatry. 2023;80(3):211–9. https://doi.org/10.1001/jamapsychiatry.2022.4448 .

Henderson A, McSkimming P, Kinnear D, McCowan C, McIntosh A, Allan L, et al. Changes over a decade in psychotropic prescribing for people with intellectual disabilities: prospective cohort study. BMJ Open. 2020;10(9):e036862. https://doi.org/10.1136/bmjopen-2020-036862 .

Rogers K, Spring B. Mental Health professionals are in high demand as the pandemic enters a Second Year. CNBC; 2022.

Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J. Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res. 2020;126:134–40. https://doi.org/10.1016/j.jpsychires.2019.08.002 .

Woody CA, Ferrari AJ, Siskind DJ, Whiteford HA, Harris MG. A systematic review and meta-regression of the prevalence and incidence of perinatal depression. J Affect Disord. 2017;219:86–92. https://doi.org/10.1016/j.jad.2017.05.003 .

Chong HY, Teoh SL, Wu DB, Kotirum S, Chiou CF, Chaiyakunapruk N. Global economic burden of schizophrenia: a systematic review. Neuropsychiatr Dis Treat. 2016;12:357–73. https://doi.org/10.2147/ndt.S96649 .

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global Epidemiology and burden of Schizophrenia: findings from the global burden of Disease Study 2016. Schizophr Bull. 2018;44(6):1195–203. https://doi.org/10.1093/schbul/sby058 .

Global, regional, and, national, burden, of, 12, mental, disorders, in, 204, countries, and, territories, 1990–2019, a, systematic, analysis, for, the, Global, Burden, of, Disease, Study, 2019. Lancet Psychiatry. 2022;9(2):137–50. https://doi.org/10.1016/s2215-0366(21)00395-3 .

Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry. 2015;72(4):334–41. https://doi.org/10.1001/jamapsychiatry.2014.2502 .

Hany M, Rehman B, Azhar Y, Chapman J. Schizophrenia. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023. StatPearls Publishing LLC.; 2023.

Sweileh WM. Analysis of global research output on diabetes depression and suicide. Ann Gen Psychiatry. 2018;17:44. https://doi.org/10.1186/s12991-018-0214-2 .

Sweileh WM. Contribution of researchers in the arab region to peer-reviewed literature on mental health and well-being of university students. Int J Ment Health Syst. 2021;15(1):50. https://doi.org/10.1186/s13033-021-00477-9 .

Falagas ME, Pitsouni EI, Malietzis GA, Pappas G. Comparison of PubMed, Scopus, web of Science, and Google Scholar: strengths and weaknesses. FASEB Journal: Official Publication Federation Am Soc Experimental Biology. 2008;22(2):338–42. https://doi.org/10.1096/fj.07-9492LSF .

Article   CAS   Google Scholar  

van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84(2):523–38. https://doi.org/10.1007/s11192-009-0146-3 .

Meltzer HY. Rigidity, hyperpyrexia and coma following fluphenazine enanthate. Psychopharmacologia. 1973;29(4):337–46. https://doi.org/10.1007/bf00429281 .

Silbergeld EK, Hruska RE. Lisuride and LSD: dopaminergic and serotonergic interactions in the serotonin syndrome. Psychopharmacology. 1979;65(3):233–7. https://doi.org/10.1007/bf00492209 .

Henderson VW, Wooten GF. Neuroleptic malignant syndrome: a pathogenetic role for dopamine receptor blockade? Neurology. 1981;31(2):132–7. https://doi.org/10.1212/wnl.31.2.132 .

Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–42. https://doi.org/10.1093/qjmed/hcg109 .

Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005;95(4):434–41. https://doi.org/10.1093/bja/aei210 .

Ueno S, Otani K, Kaneko S, Koshiro K, Kondoh K, Kotani Y, et al. Cytochrome P-450 2D6 gene polymorphism is not associated with neuroleptic malignant syndrome. Biol Psychiatry. 1996;40(1):72–4. https://doi.org/10.1016/0006-3223(95)00427-0 .

Ochi S, Kawasoe K, Abe M, Fukuhara R, Sonobe K, Kawabe K, et al. A case study: neuroleptic malignant syndrome with risperidone and CYP2D6 gene variation. Gen Hosp Psychiatry. 2011;33(6):640. https://doi.org/10.1016/j.genhosppsych.2011.03.003 . .e1-2.

Article   Google Scholar  

Kato D, Kawanishi C, Kishida I, Furuno T, Matsumura T, Hasegawa H, et al. CYP2D6 gene deletion allele in patients with neuroleptic malignant syndrome: preliminary report. Psychiatry Clin Neurosci. 2005;59(4):504–7. https://doi.org/10.1111/j.1440-1819.2005.01405.x .

Iwahashi K, Yoshihara E, Nakamura K, Ameno K, Watanabe M, Tsuneoka Y, et al. CYP2D6 HhaI genotype and the neuroleptic malignant syndrome. Neuropsychobiology. 1999;39(1):33–7. https://doi.org/10.1159/000026557 .

Iwahashi K, Nakamura K, Suwaki H, Tsuneoka Y, Ichikawa Y. CYP2D6 Hhal genotype and the neuroleptic malignant syndrome (NMS). Clin Chim Acta. 1997;265(1):143–4. https://doi.org/10.1016/s0009-8981(97)00113-7 .

Kato D, Kawanishi C, Kishida I, Furuno T, Suzuki K, Onishi H, et al. Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome. Eur J Clin Pharmacol. 2007;63(11):991–6. https://doi.org/10.1007/s00228-007-0355-8 .

Kawanishi C, Shimoda Y, Fujimaki J, Onishi H, Suzuki K, Hanihara T, et al. Mutation involving cytochrome P450IID6 in two Japanese patients with neuroleptic malignant syndrome. J Neurol Sci. 1998;160(1):102–4. https://doi.org/10.1016/s0022-510x(98)00238-x .

Kawanishi C, Hanihara T, Maruyama Y, Matsumura T, Onishi H, Inoue K, et al. Neuroleptic malignant syndrome and hydroxylase gene mutations: no association with CYP2D6A or CYP2D6B. Psychiatr Genet. 1997;7(3):127–9. https://doi.org/10.1097/00041444-199723000-00007 .

Butwicka A, Krystyna S, Retka W, Wolańczyk T. Neuroleptic malignant syndrome in an adolescent with CYP2D6 deficiency. Eur J Pediatr. 2014;173(12):1639–42. https://doi.org/10.1007/s00431-013-2208-z .

Zivković M, Mihaljević-Peles A, Sagud M, Silić A, Mihanović M. The role of CYP2D6 and TaqI a polymorphisms in malignant neuroleptic syndrome: two case reports with three episodes. Psychiatr Danub. 2010;22(1):112–6.

Mihara K, Kondo T, Suzuki A, Yasui-Furukori N, Ono S, Sano A, et al. Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome. Am J Med Genet B Neuropsychiatr Genet. 2003;117b(1):57–60. https://doi.org/10.1002/ajmg.b.10025 .

Kishida I, Kawanishi C, Furuno T, Kato D, Ishigami T, Kosaka K. Association in Japanese patients between neuroleptic malignant syndrome and functional polymorphisms of the dopamine D(2) receptor gene. Mol Psychiatry. 2004;9(3):293–8. https://doi.org/10.1038/sj.mp.4001422 .

Kishida I, Kawanishi C, Furuno T, Matsumura T, Hasegawa H, Sugiyama N, et al. Lack of association in Japanese patients between neuroleptic malignant syndrome and the TaqI a polymorphism of the dopamine D2 receptor gene. Psychiatr Genet. 2003;13(1):55–7. https://doi.org/10.1097/00041444-200303000-00010 .

Ram A, Cao Q, Keck PE Jr., Pope HG Jr., Otani K, Addonizio G, et al. Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome. Am J Med Genet. 1995;60(3):228–30. https://doi.org/10.1002/ajmg.1320600311 .

Akihito Suzuki MD, Tsuyoshi Kondo PD,, MDPD, Koichi Otani MD,, PD, Kazuo Mihara MD,, PD, Norio, Yasui-Furukori MD,, PD, Sano A,, MDPD et al. Association of the TaqI A Polymorphism of the Dopamine D2 Receptor Gene With Predisposition to Neuroleptic Malignant Syndrome. 2001;158(10):1714-6. https://doi.org/10.1176/appi.ajp.158.10.1714 .

Matsusue A, Hara K, Kageura M, Kashiwagi M, Lu W, Ishigami A, et al. Genetic analysis of ryanodine receptor 1 gene and carnitine palmitoyltransferase II gene: an autopsy case of neuroleptic malignant syndrome related to vegetamin. Leg Med (Tokyo). 2009;11(Suppl 1):S570–2. https://doi.org/10.1016/j.legalmed.2009.01.074 .

Miyatake R, Iwahashi K, Matsushita M, Nakamura K, Suwaki H. No association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated malignant hyperthermia. J Neurol Sci. 1996;143(1–2):161–5. https://doi.org/10.1016/s0022-510x(96)00015-9 .

Sato T, Nishio H, Iwata M, Kentotsuboi, Tamura A, Miyazaki T, et al. Postmortem molecular screening for mutations in ryanodine receptor type 1 (RYR1) gene in psychiatric patients suspected of having died of neuroleptic malignant syndrome. Forensic Sci Int. 2010;194(1–3):77–9. https://doi.org/10.1016/j.forsciint.2009.10.014 .

Russell T, Riazi S, Kraeva N, Steel AC, Hawryluck LA. Ecstacy-induced delayed rhabdomyolysis and neuroleptic malignant syndrome in a patient with a novel variant in the ryanodine receptor type 1 gene. Anaesthesia. 2012;67(9):1021–4. https://doi.org/10.1111/j.1365-2044.2012.07226.x .

Kawanishi C, Hanihara T, Shimoda Y, Suzuki K, Sugiyama N, Onishi H, et al. Lack of association between neuroleptic malignant syndrome and polymorphisms in the 5-HT1A and 5-HT2A receptor genes. Am J Psychiatry. 1998;155(9):1275–7. https://doi.org/10.1176/ajp.155.9.1275 .

Kaneda Y, Kawamura I, Fujii A, Ohmori T. Serotonin syndrome - ‘potential’ role of the CYP2D6 genetic polymorphism in asians. Int J Neuropsychopharmacol. 2002;5(1):105–6. https://doi.org/10.1017/s1461145701002723 .

Calmy KIL, Ambrosioni A, Assouline J, Daali B, Fathi Y. Serotonin syndrome following drug-drug interactions and CYP2D6 and CYP2C19 genetic polymorphisms in an HIV-infected patient. Aids. 2012;26(18):2417–8. https://doi.org/10.1097/QAD.0b013e32835a11ba .

Agarwal P, Omoruyi A, Perai KG, MacDaid K, Burton A. Neuroleptic malignant syndrome (NMS) on clozapine with a potential atypical Interaction with Paliperidone. Case Rep Psychiatry. 2021;2021:5584104. https://doi.org/10.1155/2021/5584104 .

Mazhar F, Akram S, Haider N, Ahmed R. Overlapping of Serotonin Syndrome with neuroleptic malignant syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide interactions: a Case Report of two serious adverse drug effects caused by Medication Reconciliation failure on Hospital Admission. Case Rep Med. 2016;2016:7128909. https://doi.org/10.1155/2016/7128909 .

Gillman PK. CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. J Psychopharmacol. 2011;25(3):429–36. https://doi.org/10.1177/0269881109359098 .

Graber MA, Hoehns TB, Perry PJ. Sertraline-phenelzine drug interaction: a serotonin syndrome reaction. Ann Pharmacother. 1994;28(6):732–5. https://doi.org/10.1177/106002809402800610 .

Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB. Interaction of serotonergic antidepressants and opioid analgesics: is serotonin syndrome going undetected? J Am Med Dir Assoc. 2005;6(4):265–9. https://doi.org/10.1016/j.jamda.2005.04.012 .

Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32(2):199–202. https://doi.org/10.1111/j.1365-2710.2007.00813.x .

Chan BS, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169(10):523–5. https://doi.org/10.5694/j.1326-5377.1998.tb123399.x .

Clark DB, Andrus MR, Byrd DC. Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature. Pharmacotherapy. 2006;26(2):269–76. https://doi.org/10.1592/phco.26.2.269 .

Bai AD, McKenna S, Wise H, Loeb M, Gill SS. Association of Linezolid with Risk of Serotonin Syndrome in patients receiving antidepressants. JAMA Netw Open. 2022;5(12):e2247426. https://doi.org/10.1001/jamanetworkopen.2022.47426 .

Karkow DC, Kauer JF, Ernst EJ. Incidence of Serotonin Syndrome with Combined Use of Linezolid and Serotonin Reuptake inhibitors compared with Linezolid Monotherapy. J Clin Psychopharmacol. 2017;37(5):518–23. https://doi.org/10.1097/jcp.0000000000000751 .

Gupta V, Karnik ND, Deshpande R, Patil MA. Linezolid-induced serotonin syndrome. BMJ Case Rep. 2013;2013. https://doi.org/10.1136/bcr-2012-008199 .

Mitwally H, Saad MO, Alkhiyami D, Fahmi AM, Mahmoud S, Hmoud EA, et al. Risk of serotonin syndrome in acutely ill patients receiving linezolid and opioids concomitantly: a retrospective cohort study. IJID Reg. 2022;5:137–40. https://doi.org/10.1016/j.ijregi.2022.09.008 .

Huang V, Gortney JS. Risk of serotonin syndrome with concomitant administration of linezolid and serotonin agonists. Pharmacotherapy. 2006;26(12):1784–93. https://doi.org/10.1592/phco.26.12.1784 .

Gatti M, Raschi E, De Ponti F. Serotonin syndrome by drug interactions with linezolid: clues from pharmacovigilance-pharmacokinetic/pharmacodynamic analysis. Eur J Clin Pharmacol. 2021;77(2):233–9. https://doi.org/10.1007/s00228-020-02990-1 .

Masbough F, Roshanzamiri S, Rahimi M, Sahraei Z, Evini PET. Serotonin syndrome due to concomitant use of linezolid and methadone. Clin Case Rep. 2022;10(11):e6341. https://doi.org/10.1002/ccr3.6341 .

Essakow J, Jin L, Marupudi N, Wattier R, McQuillen P, Franzon D. Serotonin Syndrome in an infant Associated with Linezolid and Opioid Use. J Pediatr Pharmacol Ther. 2022;27(6):564–8. https://doi.org/10.5863/1551-6776-27.6.564 .

Spigset O, Adielsson G. Combined serotonin syndrome and hyponatraemia caused by a citalopram-buspirone interaction. Int Clin Psychopharmacol. 1997;12(1):61–3. https://doi.org/10.1097/00004850-199701000-00010 .

Brubacher JR, Hoffman RS, Lurin MJ. Serotonin syndrome from venlafaxine-tranylcypromine interaction. Vet Hum Toxicol. 1996;38(5):358–61.

CAS   PubMed   Google Scholar  

Nelson EM, Philbrick AM. Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother. 2012;46(12):1712–6. https://doi.org/10.1345/aph.1Q748 .

Aboukarr A, Giudice M. Interaction between Monoamine oxidase B inhibitors and selective serotonin reuptake inhibitors. Can J Hosp Pharm. 2018;71(3):196–207.

Gray R, Moore Iii A, Berry F, Afroze F, Cherukupalli D. Serotonin Syndrome after PACU Administration of Tramadol and Meperidine. Turk J Anaesthesiol Reanim. 2022;50(4):309–11. https://doi.org/10.5152/tjar.2022.21355 .

Mateo-Carrasco H, Muñoz-Aguilera EM, García-Torrecillas JM, Abu Al-Robb H. Serotonin syndrome probably triggered by a morphine-phenelzine interaction. Pharmacotherapy. 2015;35(6):e102–5. https://doi.org/10.1002/phar.1581 .

Declercq PL, Eraldi JP, Beuzelin M, Gélinotte S, Marchalot A, Bougerol F, et al. Severe serotonin syndrome caused by an interaction between an antidepressant and a cough syrup. Therapie. 2021;76(3):249–52. https://doi.org/10.1016/j.therap.2020.02.020 .

Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018;64(10):720–7.

Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf. 2008;7(5):587–96. https://doi.org/10.1517/14740338.7.5.587 .

Chan TC, Evans SD, Clark RF. Drug-induced hyperthermia. Crit Care Clin. 1997;13(4):785–808. https://doi.org/10.1016/s0749-0704(05)70369-9 .

Horseman M, Panahi L, Udeani G, Tenpas AS, Verduzco R Jr., Patel PH, et al. Drug-Induced Hyperth Rev Cureus. 2022;14(7):e27278. https://doi.org/10.7759/cureus.27278 .

Savvidou A, Jennions E, Wikström S, Olsson-Engman M, Sofou K, Darin N. Drug-induced hyperthermia with rhabdomyolysis in CLN3 disease. Eur J Paediatr Neurol. 2022;39:74–8. https://doi.org/10.1016/j.ejpn.2022.06.007 .

Gurrera RJ, Caroff SN, Cohen A, Carroll BT, DeRoos F, Francis A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry. 2011;72(9):1222–8. https://doi.org/10.4088/JCP.10m06438 .

Gurrera RJ, Mortillaro G, Velamoor V, Caroff SN. A validation study of the International Consensus Diagnostic Criteria for neuroleptic malignant syndrome. J Clin Psychopharmacol. 2017;37(1):67–71. https://doi.org/10.1097/jcp.0000000000000640 .

Karamustafalioglu N, Kalelioglu T, Celikel G, Genc A, Emul M. Clinical utility of neutrophil-lymphocyte ratio in the diagnosis of neuroleptic malignant syndrome. Nord J Psychiatry. 2019;73(4–5):288–92. https://doi.org/10.1080/08039488.2019.1623315 .

Kalelioglu T, Celikel G, Balaban OD, Karamustafalioglu N, Penberthy JK. Can Neutrophil-Lymphocyte ratio be a useful Criterion for neuroleptic malignant syndrome in the absence of Leukocytosis? Iran J Psychiatry. 2021;16(3):370–3. https://doi.org/10.18502/ijps.v16i3.6264 .

Védie C, Poinso F, Hemmi F, Rivet B. Major symptoms and differential diagnosis of neuroleptic malignant syndrome: three case reports. Eur Psychiatry. 2000;15(5):334–7. https://doi.org/10.1016/s0924-9338(00)00403-x .

Uddin MF, Alweis R, Shah SR, Lateef N, Shahnawaz W, Ochani RK, et al. Controversies in serotonin syndrome diagnosis and management: a review. J Clin Diagn Res. 2017;11(9):Oe05–7. https://doi.org/10.7860/jcdr/2017/29473.10696 .

Jašović-Gašić M, Vuković O, Pantović M, Cvetić T, Marić-Bojović N. Antipsychotics–history of development and field of indication, new wine–old glassess. Psychiatr Danub. 2012;24(Suppl 3):S342–4.

Danilov DS. [A current view on the history of atypical antipsychotics]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(5):85–93. https://doi.org/10.17116/jnevro20171175185-93 .

De Risio A, Lang AP. History and therapeutic rationale of long acting antipsychotics. Curr Clin Pharmacol. 2014;9(1):39–52. https://doi.org/10.2174/15748847113089990057 .

Shen WW. A history of antipsychotic drug development. Compr Psychiatry. 1999;40(6):407–14. https://doi.org/10.1016/s0010-440x(99)90082-2 .

Ramachandraiah CT, Subramaniam N, Tancer M. The story of antipsychotics: past and present. Indian J Psychiatry. 2009;51(4):324–6. https://doi.org/10.4103/0019-5545.58304 .

Perez-Caballero L, Torres-Sanchez S, Bravo L, Mico JA, Berrocoso E. Fluoxetine: a case history of its discovery and preclinical development. Expert Opin Drug Discov. 2014;9(5):567–78. https://doi.org/10.1517/17460441.2014.907790 .

Margetić B, Aukst-Margetić B. Neuroleptic malignant syndrome and its controversies. Pharmacoepidemiol Drug Saf. 2010;19(5):429–35. https://doi.org/10.1002/pds.1937 .

Saha KB, Bo L, Zhao S, Xia J, Sampson S, Zaman RU. Chlorpromazine versus atypical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2016;4(4):Cd010631. https://doi.org/10.1002/14651858.CD010631.pub2 .

Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int. 2014;2014:656370. https://doi.org/10.1155/2014/656370 .

Meltzer HY. Update on typical and atypical antipsychotic drugs. Annu Rev Med. 2013;64:393–406. https://doi.org/10.1146/annurev-med-050911-161504 .

Talton CW. Serotonin Syndrome/Serotonin toxicity. Fed Pract. 2020;37(10):452–9. https://doi.org/10.12788/fp.0042 .

Sweileh WM, Sawalha AF, Al-Jabi SW, Zyoud SH, Shraim NY, Abu-Taha AS. A bibliometric analysis of literature on malaria vector resistance: (1996–2015). Globalization Health. 2016;12(1):76. https://doi.org/10.1186/s12992-016-0214-4 .

Zyoud SH, Shakhshir M, Abushanab AS, Al-Jabi SW, Koni A, Shahwan M, et al. Mapping the global research landscape on nutrition and the gut microbiota: visualization and bibliometric analysis. World J Gastroenterol. 2022;28(25):2981–93. https://doi.org/10.3748/wjg.v28.i25.2981 .

Sweileh WM. Bibliometric analysis of peer-reviewed literature on climate change and human health with an emphasis on infectious diseases. Globalization Health. 2020;16(1):44. https://doi.org/10.1186/s12992-020-00576-1 .

Sweileh WM. Global research trends of World Health Organization’s top eight emerging pathogens. Globalization Health. 2017;13(1):9. https://doi.org/10.1186/s12992-017-0233-9 .

Bilanakis N, Peritogiannis V, Kalampokis G. Infections as complications of neuroleptic malignant syndrome. World J Biol Psychiatry. 2009;10(4 Pt 3):973–6. https://doi.org/10.1080/15622970801935578 .

Taniguchi N, Tanii H, Nishikawa T, Miyamae Y, Shinozaki K, Inoue Y, et al. Classification system of complications in neuroleptic malignant syndrome. Methods Find Exp Clin Pharmacol. 1997;19(3):193–9.

Hegerl U, Bottlender R, Gallinat J, Kuss HJ, Ackenheil M, Möller HJ. The serotonin syndrome scale: first results on validity. Eur Arch Psychiatry Clin Neurosci. 1998;248(2):96–103. https://doi.org/10.1007/s004060050024 .

Modi S, Dharaiya D, Schultz L, Varelas P. Neuroleptic malignant syndrome: complications, outcomes, and Mortality. Neurocrit Care. 2016;24(1):97–103. https://doi.org/10.1007/s12028-015-0162-5 .

Park JI, Park TW. Rhabdomyolysis and Neuroleptic Malignant Syndrome Associated with very low-dose antipsychotics in children and adolescent. Clin Psychopharmacol Neurosci. 2019;17(3):450–2. https://doi.org/10.9758/cpn.2019.17.3.450 .

Desai S, Hirachan T, Toma A, Gerolemou A. Malignant Catatonia Versus neuroleptic malignant syndrome. Cureus. 2021;13(6):e15818. https://doi.org/10.7759/cureus.15818 .

Shouan A, Kumar R, Lal V, Grover S. Linezolid-induced serotonin syndrome. Ind Psychiatry J. 2020;29(2):345–8. https://doi.org/10.4103/ipj.ipj_37_19 .

Keltner N, Harris CP. Serotonin syndrome: a case of fatal SSRI/MAOI interaction. Perspect Psychiatr Care. 1994;30(4):26–31. https://doi.org/10.1111/j.1744-6163.1994.tb00446.x .

Park SH, Wackernah RC, Stimmel GL. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants? J Pharm Pract. 2014;27(1):71–8. https://doi.org/10.1177/0897190013504957 .

Beakley BD, Kaye AM, Kaye AD, Tramadol. Pharmacology, Side effects, and Serotonin Syndrome: a review. Pain Physician. 2015;18(4):395–400.

Hassamal S, Miotto K, Dale W, Danovitch I. Tramadol: understanding the risk of serotonin syndrome and seizures. Am J Med. 2018;131(11):1382. e1-.e6 https://doi.org/10.1016/j.amjmed.2018.04.025 .

Ruiz de Villa A, Jones T, Lleshi A, Macahuachi M, Lamar K, Bazikian Y. Serotonin toxicity precipitated by Tramadol in the setting of polypharmacy: a case of Serotonin Syndrome. Cureus. 2021;13(11):e20059. https://doi.org/10.7759/cureus.20059 .

Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16(4):615–9. https://doi.org/10.1016/s0736-4679(98)00057-2 .

Deardorff OG, Khan T, Kulkarni G, Doisy R, Loehr C. Serotonin Syndrome: Prophylactic Treatment with Cyproheptadine. Prim Care Companion CNS Disord. 2016;18(4). https://doi.org/10.4088/PCC.16br01966 .

Lappin RI, Auchincloss EL. Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med. 1994;331(15):1021–2. https://doi.org/10.1056/nejm199410133311514 .

Baldo BA. Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity. Arch Toxicol. 2021;95(8):2627–42. https://doi.org/10.1007/s00204-021-03068-2 .

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Aberrant left coronary artery from the pulmonary artery with patent ductus arteriosus - a case report and review of the literature

• Ahmad Amer   ORCID: orcid.org/0000-0002-1626-302X 1 , 2 ,
• Hanita Shai 1 , 2 ,
• Sagi Assa 1 , 2 ,
• Avital Mitler 1 , 2 &
• Alona Raucher Sternfeld 1 , 2  

Journal of Cardiothoracic Surgery volume  19 , Article number:  319 ( 2024 ) Cite this article

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Aberrant left coronary artery from pulmonary artery (ALCAPA) is a very rare congenital heart defect. Its coexistence with patent ductus arteriosus (PDA) is extremely rare. The high pressures created by the left-to-right shunt in the pulmonary arteries can delay symptoms and create a real challenge in diagnosing ALCAPA. Missing this diagnosis can have severe results, including extensive ischemia and sudden death.

Case presentation

We present a case of an infant born with a large PDA. Initially treated conservatively, however, due to congestive heart failure and lack of weight gain, she underwent surgical ligation of the PDA at the age of four and a half months. Following surgery, she developed pulmonary edema. Echocardiography revealed decreased ventricular function. ECG revealed ST elevations on lateral leads, and serum troponin was significantly increased. The patient underwent cardiac magnetic resonance imaging (MRI), which revealed signs of wall ischemia and decreased function of the left ventricle (LV) with unclear coronary anatomy. Diagnostic catheterization revealed an ALCAPA. She underwent surgical intervention, and the left coronary artery was re-implanted in the aortic sinus. Follow-up revealed slow improvement of cardiac function.

Discussion and literature review

The coexistence of PDA and ALCAPA is a very rare occurrence. We found at least 10 reported cases in the literature. Delayed diagnosis might be detrimental. The prognosis of these patients is variable.

An unusual post-surgical course following PDA repair requires a high index of suspicion and appropriate evaluation for ALCAPA, preferably with angiography.

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ALCAPA, also known as Bland-White-Garland syndrome, is a rare coronary abnormality, constituting 0.3–0.5% of congenital heart defects [ 1 , 2 , 3 ]. Left untreated, it can cause mortality in 90% of cases [ 2 , 3 ]. Survival into adulthood is probably due to collateral development in the coronary circulation, with the risk of sudden death remaining high [ 4 , 5 , 6 ].

ALCAPA is, in most cases, an isolated defect, but in rare incidences, it has been described with other anomalies like tetralogy of Fallot, coarctation of the aorta, ventricular septal defects, and PDA ( 7 – 8 ).

ALCAPA is asymptomatic in the fetal period, as the pressures and oxygen saturations are similar in the great arteries. Following birth, the pressure in the pulmonary artery gradually decreases to a point where the coronary perfusion pressure, that is the difference between the pressure in the coronary artery and the LV wall pressure, is not adequate and ischemia ensues. This, in turn, causes dysfunction of the left ventricle, dilation of the left side of the heart, and mitral regurgitation, reflected as clinical heart failure and, in some cases, arrhythmias and sudden death [ 1 , 9 ].

We report a case of ALCAPA masked by a large PDA in an infant female. Informed consentwas acquired from the patient’s guardian for this report.

A female infant was born with a large PDA. She developed early congestive heart failure and was initially treated conservatively with diuretics, ACE inhibitors, and high-caloric feeding, and followed up in the pediatric cardiology clinic.

Repeat echocardiography showed a PDA 4–5 mm in diameter with a left-to-right shunt across and a low-pressure gradient. The left atrium, left ventricle, and pulmonary arteries were all dilated, as expected. Cardiac function was normal and hyperdynamic in some tests. The coronaries were reported to be normal in origin and course in multiple tests by experienced sonographists and pediatric cardiologists (Fig. 1 ).

The original management plan was to allow the patient to gain enough weight, making trans-catheter device occlusion of the PDA feasible. However, weekly follow-ups indicated worsening congestive heart failure, reflected by failure to thrive as well as recurrent respiratory infections requiring hospitalization.

Following prolonged hospitalization due to RSV bronchiolitis at the age of 4 months and the persistent lack of weight gain, it was decided to perform surgical ligation of the PDA. At the age of 4.5 months, the PDA was ligated through a lateral thoracic incision with an unremarkable surgical course.

Following surgery, on post-surgical day (POD) 2, the patient was weaned off mechanical ventilation and catecholamine support. However, dyspnea, tachypnea, and tachycardia persisted. Chest X-ray on POD 3 revealed worsening congestion. Additionally, the ECG which had been normal up to POD 2, began to exhibit pronounced ST elevations on anterior and lateral leads on POD 3 and 4 (Fig. 2 ). Echocardiography revealed significantly decreased left ventricle function, assessed through “eyeballing” and fractional shortening measurement of 10–15%. Echocardiography did not explain the findings; the coronary anatomy was investigated thoroughly by multiple pediatric cardiologists and reported as normal. Troponin was measured and found to be significantly increased, reaching a maximum of 5330 ng/L.

A differential diagnosis was suggested, including an iatrogenic surgical cause, infectious myocarditis, and coronary anomalies missed in the echocardiography.

Following an extensive interdisciplinary consultation, during which the possibility of conducting further diagnostic tests such as computed tomography (CT) imaging was entertained, it was ultimately determined that pursuing a cardiac magnetic resonance imaging (MRI) examination would offer the most clinically informative approach, particularly in the context of the complex array of potential differential diagnoses under consideration. Subsequently, on POD 6,the patient underwent a cardiac MRI, which revealed thinning of the myocardium and hypokinesia of the lateral wall and septum, increased T2- weighted signal indicating edema, and late gadolinium enhancement of the endocardium (Fig. 3 – 4 ). The left ventricle and atrium were dilated, with a left ventricular ejection fraction measured at 20%. The coronary anatomy was not clear.

On POD 7, she underwent pulmonary artery angiography, confirming the diagnosis of ALCAPA (Fig. 5 ).

She underwent emergent surgical intervention on the same day, during which the left coronary artery was successfully re-implanted in the aortic sinus. The surgery was without complications. She was weaned off cardiopulmonary pump easily and transferred to the pediatric intensive care unit (PICU).

Following surgery, she had a prolonged course due to decreased LV function. Extubation was performed on POD 5, and she was completely weaned off catecholamine support by POD 12. Her PICU length of stay was 25 days, and the total length of stay was 30 days. Prior to discharge, troponin decreased to 358 ng/L, and echocardiography revealed some improvement of cardiac function.

Since her discharge, seven months ago as of the writing of this report, she has been re-hospitalized a total of 7 times. The first re-hospitalization has been just 5 days following her discharge. Most readmissions were due to social factors; however, in two cases, she had respiratory infections with decompensation of her heart failure requiring PICU hospitalization.

Follow-up revealed slow and gradual improvement of cardiac function with wall motion abnormalities and dilated cardiomyopathy. Due to slow improvement, she completed a coronary CT and invasive angiography, both demonstrated patent coronaries arising from the aorta. Her last follow-up was at the age of eleven months, seven months following surgery. She appears well with only mild tachypnea and is gaining weight slowly. Echocardiography revealed dilated LV and left atrium, lateral and septal wall motion abnormalities, and fractional shortening of 23%. The re-implanted left coronary artery appeared patent with normal flow. She continues medical treatment and receives furosemide, captopril, and digoxin, which she tolerates well.

The combination of ALCAPA and PDA is extremely rare. One paper by Wesselhoeft et al., reviewing 140 cases of ALCAPA, found only one case associated with PDA [ 9 ].

The pathophysiology of ALCAPA is usually a gradual decrease of blood supply to the myocardium as the pulmonary pressure decreases following birth [ 9 ].

The presence of a sizable arterial duct with a large shunt into the pulmonary artery increases the pressure in the vessel which in turn sustains sufficient perfusion to the left coronary artery, consequently delaying clinical presentation until the duct is ligated [ 10 ]. The combination of PDA and ALCAPA is thus gravely dangerous, as the PDA not only complicates the diagnosis of ALCAPA but can also produce catastrophic ischemia when it is repaired ( 11 – 10 , 12 ).

We reviewed the literature for all available publications reporting on a combination of PDA and ALCAPA in infants. We searched PubMed for the terms PDA AND ALCAPA and augmented our search with Google Scholar and the regular Google search engine. We chose to omit adult cases, given that the pathophysiology might be different. We found at least 10 reported cases in the literature, which are presented in Table  1 .

Most infants initially present with congestive heart failure (CHF) in the first months of life. All cases, including ours, report normal LV function in the initial presentation; some have mitral regurgitation (MR), which, along with the CHF, is attributed to the large PDA. A specific finding of hyperechoic papillary muscle was reported in four of the ten cases [ 12 , 16 , 17 , 18 ].

ALCAPA was recognized in three cases prior to surgery. In two cases, it was recognized incidentally during diagnostic catheterization [ 13 , 17 ]. In the third case, it was diagnosed by transthoracic echocardiography (TTE) [ 16 ].

The clinical presentation following PDA closure is dramatic in all cases. Most develop immediate hemodynamic shock or ventricular arrhythmia [ 12 , 14 , 18 , 19 ], and some develop CHF with severely decreased LV function ( 11 – 10 , 15 ). The diagnosis of ALCAPA following PDA repair might be delayed, especially in cases with a non-catastrophic presentation. In one case, the diagnosis was delayed for 2 years [ 11 ]; however, this was an out-of-country case where the local staff might have had limited resources. In another case, the infant improved clinically following PDA closure, and the diagnosis was only made 16 days following the surgery during a routine TTE [ 15 ]. In our case, the patient didn’t present dramatically following the PDA closure. As mentioned, she was weaned off catecholamine support and invasive ventilation and developed pulmonary edema on POD 3 and 4. This relatively mild course might have contributed to the delay in the diagnosis.

Angiography remains the gold standard for ALCAPA diagnosis; this is also reflected in the cases described in this paper. TTE can be very effective in finding this diagnosis, but the combination with PDA might limit its utility. This observation may be attributed to the substantial jet generated by the PDA into the pulmonary artery, along with the normal flow direction in the aberrant coronary artery [ 8 ]. In our case, apart from TTE, the first modality chosen was cardiac MRI. This was to rule out other considered diagnoses, specifically myocarditis. MRI use is not common in this context. In our case, though it didn’t directly reveal the ALCAPA, it strongly suggested it, and the diagnosis was finalized via angiography as mentioned before.

The prognosis of these patients is variable. Three patients died: one was diagnosed with a significant delay of two years and didn’t survive the surgery [ 11 ], another, diagnosed on POD 2 after duct ligation, also didn’t survive the re-implantation procedure [ 10 ]. Both of these cases are from the 80s; surgical and anesthesia techniques and expertise have evolved since. The third case of mortality described an infant with severe comorbidity, a hypoplastic aortic arch, who was diagnosed in the operating room following weaning off bypass; he also didn’t survive the surgery [ 19 ].

For surviving patients, prognosis appears to be good, although it was only described in four of the seven living cases [ 12 , 15 , 17 , 18 ]. The long-term prognosis of patients with isolated ALCAPA is reported to be good [ 20 , 21 ]. A large series describing more than 100 patients four years after corrective surgery reported very low mortality and normalization of the LV function in almost all patients [ 21 ].

In our case, seven months after surgical repair, the patient unfortunately continues to have a dilated LV with decreased fractional shortening, however, she is gaining weight gradually and managed mostly in the ambulatory setting.

The combination of ALCAPA and PDA carries a special risk. High awareness must be maintained, and any clues for the diagnosis have to be fully pursued prior to PDA repair. An unusual post-surgical course following PDA repair requires a high index of suspicion and immediate appropriate evaluation for ALCAPA, preferably with angiography.

Coronary echocardiographic imaging prior to surgery

ECG on POD 4revealing ST segment elevations

Cardiac MRI scan T2-weighted signal- Lateral LV wall edema

Cardiac MRI scan - Diffuse LV late gadolinium enhancement

Pulmonary artery angiography – LMCA arising from the pulmonary artery

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Aberrant Left Coronary Artery from Pulmonary Artery

Congenital Heart Disease

Ventricular Septal Defect

Patent Ductus Arteriosus

Left Ventricle

Transthoracic Echocardiography

Pediatric Intensive Care Unit

Post-Operative Day

Congestive Heart Failure

Mitral Regurgitation

Left Main Coronary Artery

Hauser M. Congenital anomalies of the coronary arteries. Heart. 2005;91(9):1240–5.

Article   PubMed   PubMed Central   Google Scholar  

Peña E, Nguyen ET, Merchant N, Dennie C. ALCAPA Syndrome: not just a Pediatric Disease. Radiographics. 2009;29(2):553–65.

Article   PubMed   Google Scholar  

Kristensen T, Kofoed KF, Helqvist S, Helvind M, Søndergaard L. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) presenting with ventricular fibrillation in an adult: a case report. J Cardiothorac Surg. 2008;3(1).

‌Takimura CK, Nakamoto A, Hotta VT, Campos MF, Málamo M, Otsubo R. Anomalous origin of the left coronary artery from the Pulmonary artery: report of an adult case. Arquivos brasileiros de cardiologia. 2002;78(3).

Khanna A, Torigian DA, Ferrari VA, Bross RJ, Rosen MA. Anomalous origin of the left coronary artery from the pulmonary artery in Adulthood on CT and MRI. Am J Roentgenol. 2005;185(2):326–9.

Article   Google Scholar  

Yau JM, Singh P, Halpern EJ, Fischman DL. Anomalous origin of the left coronary artery from the pulmonary artery in adults: a Comprehensive Review of 151 adult cases and a new diagnosis in a 53-Year-old woman. Clin Cardiol. 2011;34(4):204–10.

‌Ojha V, Niraj Nirmal Pandey, Kumar S, Ramakrishnan S, Priya Jagia. Anomalous origin of left main coronary artery from pulmonary artery: patient characteristics and imaging associations on multidetector computed tomography angiography. J Card Surg. 2021;36(11):4043–53.

Laux D, Bertail C, Bajolle F, Houyel L, Boudjemline Y, Bonnet D. Anomalous left coronary artery connected to the Pulmonary Artery Associated with other Cardiac defects: a difficult joint diagnosis. Pediatr Cardiol. 2014;35(7):1198–205.

‌H. Wesselhoeft, Fawcett JS, Johnson A. Anomalous origin of the left coronary artery from the pulmonary trunk. 1968;38(2):403–25.

‌Sreeram N, Hunter S, Wren C. Acute myocardial infarction in infancy: unmasking of anomalous origin of the left coronary artery from the pulmonary artery by ligation of an arterial duct. Heart. 1989;61(3):307–8.

‌Ortiz E, de Leval M, Somerville J. Ductus arteriosus associated with an anomalous left coronary artery arising from the pulmonary artery: catastrophe after duct ligation. Heart. 1986;55(4):415–7.

Walker TC, Renno MS, Parra DA, Guthrie SO. Neonatal ventricular fibrillation and an elusive ALCAPA: things are not always as they seem. BMJ Case Rep. 2016;2016:bcr2015214239.

‌Kiliç A, Elshershari H, Ozkutlu S. Anomalous left coronary artery from the main pulmonary trunk: physiologic and clinical importance of its association with patent ductus arteriosus and pulmonary hypertension. Turk J Pediatr. 2002;44(4):363–5.

PubMed   Google Scholar  

Bafani E, Shukla AC, DiNardo JA. Unrecognized anomalous origin of the left coronary artery from the pulmonary artery as a cause of ventricular Fibrillation after Patent Ductus Arteriosus Ligation in an infant. Anesth Analgesia. 2007;104(1):81–3.

‌Law MA, Dean E, McKenzie, Slesnick TC, Mott AR. Anomalous left coronary artery from the pulmonary artery in a Preterm Infant: Presentation after Ligation of Ductus Arteriosus. Congenital Heart Disease., ; 2009. Published online May 1.

‌Neeraj Awasthy, Marwah A, Sharma R, Dalvi B. Anomalous origin of the left coronary artery from the pulmonary artery with patent ductus arteriosus: a must to recognize entity. Eur J Echocardiography. 2010;11(8):E31–31.

Google Scholar  

‌Aggarwal S, Delius RE, Pettersen MD. Anomalous left coronary artery from the Pulmonary artery with a large patent Ductus Arteriosus: aversion of a catastrophe. Congenit Heart Dis. 2012;8(6):E168–73.

Fudulu D, Tulloh R, Wolf A, Parry AJ, Stoica S. Anomalous left coronary from the pulmonary artery presenting as ventricular Fibrillation after Persistent Ductus Arteriosus Ligation. Ann Thorac Surg. 2015;100(1):e9–10.

Bing Z, Liu L, Chen R, Cao Q, Wen G. Case Report: neonatal complex congenital heart Disease with Anomalous Origin of the left coronary artery from the right pulmonary artery: analysis of missed diagnosis and improvement procedures. Front Pead. 2022;9.

Lange R, Cleuziou J, Krane M, et al. Long-term outcome after anomalous left coronary artery from the pulmonary artery repair: a 40-year single-centre experience. Eur J Cardiothorac Surg. 2017;53(4):732–9.

Radman M, Mastropietro CW, Costello JM, et al. Intermediate outcomes after Repair of Anomalous Left Coronary Artery from the pulmonary artery. Ann Thorac Surg. 2021;112(4):1307–15.

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A.A. wrote and edited manuscript H.S. provided imaging insight and prepared the MRI imaging and reviewed the text S.A. provided invasive catheterization insight and image and reviewed the text A.M. helped research the literature. A.R. supervised and reviewed the text.

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Amer, A., Shai, H., Assa, S. et al. Aberrant left coronary artery from the pulmonary artery with patent ductus arteriosus - a case report and review of the literature. J Cardiothorac Surg 19 , 319 (2024). https://doi.org/10.1186/s13019-024-02803-x

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