Review for 10.1186/s12876-024-03454-x (2024)

Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 1 Date: 19 Aug 2024
Reviewer's report:
Dear Authors,
The study presents a compelling exploration of the relationship between depression and
constipation using both observational and causal inference methods. Based on the strengths
of your study, including the use of large-scale observational data and rigorous MR analysis, I
recommend that the manuscript undergo revision before publication.
My detailed comments and recommendations for revision are as follows:
1.Clarify the study objectives and conclusions
The introduction could be more concise in stating the primary research question and the gaps
in current knowledge that your study aims to fill. Clarify upfront that you aim to investigate the
bidirectional causal relationship between depression and constipation, including the influence
of depression severity.
The conclusions could be more explicit about the clinical implications of your findings. For
example, suggest specific clinical interventions or screening strategies based on your results.
2.Strengthen the literature review
Expand the literature review to cover more recent studies on the association between depression
and constipation. Compare and contrast your findings with those of previous research,
highlighting the novel contributions of your study.
Discuss limitations of previous studies that your current approach addresses, such as the use of
single NHANES cycles or the lack of causal inference.
3.Provide more details on statistical methods
Explain the statistical methods used in more depth, especially for readers who may not be
familiar with Mendelian randomization (MR) analysis. For instance, provide a brief overview
of IVW, MR-Egger, and the weighted median methods.
Clarify how you determined the thresholds for selecting single nucleotide polymorphisms
(SNPs) and why you chose P < 5×10^-6 rather than a stricter cutoff.
4.Address potential limitations more thoroughly
Acknowledge and discuss potential limitations more extensively. For example, discuss the
possibility of bias in PHQ-9 and BSFS measurements and the impact of unmeasured
confounding variables.
Comment on the lack of data on constipation duration and severity, and how this may impact
the generalizability of your findings.
Acknowledge that your study only included populations from the United States and Europe and
suggest directions for future research in other ethnic groups.
5.Enhance the discussion of results
Provide a more nuanced interpretation of your results, especially regarding the higher risk ratio
of constipation in depression compared to major depression. Explore potential explanations,
such as antidepressant use, and suggest directions for future research to clarify this finding.
Discuss the implications of your findings for clinical practice, including recommendations for
screening and managing constipation in patients with depression.
6.Improve clarity and readability
Shorten and refine the introduction and discussion sections to improve clarity and readability.
Focus on the most relevant background information and directly relate it to your research
question and findings.
Ensure consistency in terminology and define technical terms the first time they are used.
7.Correct any typographical or grammatical errors
Thoroughly proofread the manuscript to correct any typographical or grammatical errors that
may distract from the content.