A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes

Round 1

Reviewer 1 Report

Following a study of the submitted research, "A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes," I have identified various areas for improvement and possible solutions to address these issues:

1. Low Danger of Bias in Assessment.

The study does not contain a rigorous risk of bias assessment for the included studies, which might aid in determining the quality of the evidence given.

The authors should conduct a risk of bias assessment using a standardized technique (e.g., Cochrane Risk of Bias technique, Newcastle-Ottawa Scale) to assess the quality of the included studies and describe how study quality may influence the review's conclusions.

2. Lack of Meta-Analysis.

The absence of a meta-analysis may impede the quantitative synthesis of data and the evaluation of impact sizes between studies.

If feasible, the authors should consider conducting a meta-analysis of appropriate outcome measures to offer a more quantitative overview of the data. If a meta-analysis is not possible, explain the reasons and limitations of the publication.

3. Potential Publication Bias.

The study is based entirely on published publications from indexed journals, which may induce publication bias by ignoring unpublished or gray material.

The authors must broaden their search to include grey literature, such as conference proceedings, theses, and dissertations. Discuss the potential influence of publication bias on the review's results. Consider employing statistical approaches (e.g., funnel plots, Egger's test) to identify publication bias if a meta-analysis is performed.

4. Generalizability Issues.

The geographic diversity of the included research may bring cultural subtleties that influence the results' interpretation and generalizability.

The authors must describe and explain the possible constraints of generalizability owing to cultural variations and emphasize the necessity for future studies to look into the consistency of findings across diverse cultural contexts.

5. Methodological Heterogeneity.

The variability in study designs (e.g., cross-sectional, longitudinal, and randomized controlled trials) may alter the findings' comparability and synthesis.

The authors must explain and justify the consequences of methodological heterogeneity on the interpretation of findings, and if a meta-analysis is undertaken, consider doing subgroup analyses depending on the research design.

6. Minor Linguistic and Formatting Problems.

Issues include typographical and grammatical problems, difficult phrase constructions, terminology discrepancies, and transitions between parts that may be improved.

The authors must proofread thoroughly to discover and eliminate any remaining errors, simplify complicated phrases, guarantee consistent terminology usage, and optimize transitions between parts for improved readability and clarity.

7. Limited Mention of Future Research Directions.

The study might benefit from a more in-depth discussion of future research directions based on the noted gaps and limitations in the present data.

The authors must expand the discussion section to include specific areas for future research, such as looking into the role of gene-environment interactions, investigating the impact of digital technologies on substance use behaviors, and conducting longitudinal studies to better understand the causal relationships between risk factors and SUD outcomes.

By addressing these concerns, the authors can improve the quality and effect of their review, resulting in a more thorough and rigorous synthesis of the available data on the determinants of substance use disorder and co-occurring mental health conditions. 

Author Response

Following a study of the submitted research, "A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes," I have identified various areas for improvement and possible solutions to address these issues:

1. Low Danger of Bias in Assessment.

The study does not contain a rigorous risk of bias assessment for the included studies, which might aid in determining the quality of the evidence given.

The authors should conduct a risk of bias assessment using a standardized technique (e.g., Cochrane Risk of Bias technique, Newcastle-Ottawa Scale) to assess the quality of the included studies and describe how study quality may influence the review's conclusions.

RESPONSE 1: Thank you for your suggestions. Our study design is a literature review that incorporates a systematic search. We utilized the PRISMA methodology to ensure the selection process of the studies was both clear and transparent. We did not use tools such as the Cochrane Risk of Bias 2 or the Newcastle-Ottawa Scale, as these are primarily used in systematic reviews. Our review included various types of studies other than randomized controlled trials, making these tools inappropriate for our purposes. However, we plan to use these tools in future systematic reviews to enhance the quality of the evidence provided and minimize potential bias in the articles included and analyzed. Thank you again for your valuable feedback.

2. Lack of Meta-Analysis.

The absence of a meta-analysis may impede the quantitative synthesis of data and the evaluation of impact sizes between studies.

If feasible, the authors should consider conducting a meta-analysis of appropriate outcome measures to offer a more quantitative overview of the data. If a meta-analysis is not possible, explain the reasons and limitations of the publication.

RESPONSE 2: Thank you for your feedback. We acknowledge the value of a meta-analysis in providing a quantitative synthesis of data and evaluating the impact sizes between studies. However, in our literature review, we aim to provide a comprehensive overview of the existing literature on a topic, including various types of studies. The heterogeneity of these studies, in terms of their design, methodology, and outcome measures, makes it challenging to conduct a meta-analysis. Moreover, a meta-analysis requires a high level of homogeneity among the included studies, particularly regarding the outcome measures. In our work, the included studies had diverse outcome measures, which would make a meta-analysis inappropriate. We appreciate your suggestion and will consider conducting a meta-analysis in future research where it is feasible and appropriate. Thank you again for your valuable input.

3. Potential Publication Bias.

The study is based entirely on published publications from indexed journals, which may induce publication bias by ignoring unpublished or gray material.

The authors must broaden their search to include grey literature, such as conference proceedings, theses, and dissertations. Discuss the potential influence of publication bias on the review's results. Consider employing statistical approaches (e.g., funnel plots, Egger's test) to identify publication bias if a meta-analysis is performed.

RESPONSE 3: Thank you for your feedback. We have already included a significant amount of grey literature in our review. This includes annual reports, technical reports from organizations (e.g., World Drug Report 2023; three reports of NIDA.NIH.GOV | National Institute on Drug Abuse (NIDA); Global Report on Cocaine 2023), and thanks to your suggestions we added even more (e.g., a thesis, other reports, and blog posts). We hope this addresses your concerns. We are open to further suggestions and discussions to improve our work. Thank you again for your valuable input.

4. Generalizability Issues.

The geographic diversity of the included research may bring cultural subtleties that influence the results' interpretation and generalizability.

The authors must describe and explain the possible constraints of generalizability owing to cultural variations and emphasize the necessity for future studies to look into the consistency of findings across diverse cultural contexts.

RESPONSE 4: Thank you for your suggestion. Acknowledgments concerning the generalizability issues have been incorporated into the 'Limitations' subsection within the 'Discussion' section of our manuscript. Thank you for your valuable feedback.

5. Methodological Heterogeneity.

The variability in study designs (e.g., cross-sectional, longitudinal, and randomized controlled trials) may alter the findings' comparability and synthesis.

The authors must explain and justify the consequences of methodological heterogeneity on the interpretation of findings, and if a meta-analysis is undertaken, consider doing subgroup analyses depending on the research design.

RESPONSE 5: Thank you for your suggestion. We addressed the impact of methodological heterogeneity on result interpretation in the "Limitations" subsection of the "Discussion" section (lines 753-756). 

6. Minor Linguistic and Formatting Problems.

Issues include typographical and grammatical problems, difficult phrase constructions, terminology discrepancies, and transitions between parts that may be improved.

The authors must proofread thoroughly to discover and eliminate any remaining errors, simplify complicated phrases, guarantee consistent terminology usage, and optimize transitions between parts for improved readability and clarity.

RESPONSE 6: Thank you for your feedback. We have taken your suggestions into account and have conducted a thorough proofreading of the manuscript. This includes addressing typographical and grammatical errors, simplifying complex phrases, ensuring consistent terminology, and improving transitions for better readability and clarity. Thank you for your valuable input.

7. Limited Mention of Future Research Directions.

The study might benefit from a more in-depth discussion of future research directions based on the noted gaps and limitations in the present data.

The authors must expand the discussion section to include specific areas for future research, such as looking into the role of gene-environment interactions, investigating the impact of digital technologies on substance use behaviors, and conducting longitudinal studies to better understand the causal relationships between risk factors and SUD outcomes.

RESPONSE 7: Thank you for your valuable feedback. We have addressed the points you raised in the "Future research" subsection of the "Discussion" section. This includes a more in-depth discussion of future research directions based on the identified gaps and limitations in the current data. We have also outlined specific areas for future research, such as examining gene-environment interactions, exploring the impact of digital technologies on substance use behaviors, and conducting longitudinal studies to better understand the causal relationships between risk factors and SUD outcomes. We appreciate your suggestions and believe they have enriched our manuscript.

By addressing these concerns, the authors can improve the quality and effect of their review, resulting in a more thorough and rigorous synthesis of the available data on the determinants of substance use disorder and co-occurring mental health conditions.

Reviewer 2 Report

The review manuscript explores the complex factors contributing to Substance Use Disorder (SUD) and associated psychiatric symptoms. It identifies drug misuse as a global concern, with various psychoactive substances impacting addiction vulnerability. Gender and age disparities in SUD prevalence are noted, along with common comorbidities with psychiatric disorders. The research aims to inform prevention strategies and treatment recommendations by analyzing biological, social, and psychological factors influencing SUD development.

Overall, the manuscript is well-structured and appropriately cites relevant references, offering valuable insights and future research directions on a pertinent public health issue.

However, I have a major concern regarding the usage of search terms and eligibility criteria. Upon attempting to replicate the search using the exact phrases provided in lines 145-152, the PubMed search engine did not yield the expected 138,737 records, even when combining the four strings and certainly not when restricting the search to articles from 2022 onwards. Therefore, I request clarification and, if necessary, additional information in the methods section regarding the search strings and criteria.

Additionally, according to guidance from PubMed help, searches using phrases should ideally incorporate parentheses or quotes (e.g., “substance use disorder”) to refine the search results.

Author Response

The review manuscript explores the complex factors contributing to Substance Use Disorder (SUD) and associated psychiatric symptoms. It identifies drug misuse as a global concern, with various psychoactive substances impacting addiction vulnerability. Gender and age disparities in SUD prevalence are noted, along with common comorbidities with psychiatric disorders. The research aims to inform prevention strategies and treatment recommendations by analyzing biological, social, and psychological factors influencing SUD development.

Overall, the manuscript is well-structured and appropriately cites relevant references, offering valuable insights and future research directions on a pertinent public health issue.

However, I have a major concern regarding the usage of search terms and eligibility criteria. Upon attempting to replicate the search using the exact phrases provided in lines 145-152, the PubMed search engine did not yield the expected 138,737 records, even when combining the four strings and certainly not when restricting the search to articles from 2022 onwards. Therefore, I request clarification and, if necessary, additional information in the methods section regarding the search strings and criteria.

Additionally, according to guidance from PubMed help, searches using phrases should ideally incorporate parentheses or quotes (e.g., “substance use disorder”) to refine the search results.

RESPONSE: Thank you for your comment. We used Primo VE - Discovery as a tool for aggregating results across databases, which itself operates a cut-off to the results shown (regardless of filters). We will provide a clarification for this aspect in the methods section, as you suggested. Additionally, the reason we incorporated the search strings in a format without quotes is because Primo VE - Discovery utilizes such a format. We appreciate your understanding.

Round 2

Reviewer 1 Report

1. Introduction: 

The introduction may benefit from providing a clearer roadmap of the article structure upfront.

Need to strengthen the rationale for why this comprehensive review is needed/important.

2. Biological Factors Section:

Organize subsections more consistently (e.g., have a "Genetic and neurobiological factors" subsection for each drug class).

This section could benefit from smoother transitions between topics. 

3. Psychological Factors Section:

Lead with a clearer topic sentence for each subsection to orient the reader.

Provide more context when introducing certain disorders and their relationship to SUD.

Please make sure that each paragraph has a clear central point.

 4. Social Factors Section:

Make more explicit connections back to the central topic of SUD.

Add 1-2 sentences of synthesis at the end of each subsection.

5. Interaction of Factors Section:

Provide a stronger organizing framework for this section.

Develop the explanations of certain key interrelationships more fully.

Tie each example back to the central theme more explicitly.

 6. Discussion and Conclusions:

Synthesize the key takeaways more cohesively.

Expand on the practical implications of the findings for prevention and treatment

Discuss limitations more extensively, including potential biases in the reviewed literature.

Outline more specific directions for future studies based on current gaps.

Proofread closely for grammar, word choice, and flow. 

Author Response

1. Introduction: 

The introduction may benefit from providing a clearer roadmap of the article structure upfront.

Need to strengthen the rationale for why this comprehensive review is needed/important.

Thank you for your suggestions! We have revised the introduction to provide a clearer roadmap of the article structure upfront. Readers will now have a better understanding of what to expect. Additionally, we have strengthened the rationale for why this comprehensive review is essential. The importance of the topic is now more evident.

2. Biological Factors Section:

Organize subsections more consistently (e.g., have a "Genetic and neurobiological factors" subsection for each drug class).

This section could benefit from smoother transitions between topics. 

Thank you for this suggestion! Transitions between topics within this section have been smoothed out for better readability.

3. Psychological Factors Section:

Lead with a clearer topic sentence for each subsection to orient the reader.

Provide more context when introducing certain disorders and their relationship to SUD.

Please make sure that each paragraph has a clear central point.

Thank you for this suggestion! We’ve provided additional context when talking about specific disorders and their relationship to Substance Use Disorder (SUD). Paragraphs within this section have been refined to maintain a clear central point.

4. Social Factors Section:

Make more explicit connections back to the central topic of SUD.

Add 1-2 sentences of synthesis at the end of each subsection.

Thank you for your suggestion!  We made sure there are explicit connections back to the central topic of SUD throughout this section.

5. Interaction of Factors Section:

Provide a stronger organizing framework for this section.

Develop the explanations of certain key interrelationships more fully.

Tie each example back to the central theme more explicitly.

Thank you for your suggestion! Explanations of key interrelationships have been developed more fully, enhancing clarity.

6. Discussion and Conclusions:

Synthesize the key takeaways more cohesively.

Expand on the practical implications of the findings for prevention and treatment

Discuss limitations more extensively, including potential biases in the reviewed literature.

Outline more specific directions for future studies based on current gaps.

Thank you for your suggestions! We’ve synthesized the key takeaways more cohesively, emphasizing the main findings. Practical implications for prevention and treatment have been expanded upon. The discussion now includes a thorough exploration of limitations, including potential biases in the reviewed literature. Specific directions for future studies based on current gaps have been outlined.