Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 1 Date: 29 Aug 2024
Reviewer's report:
The study included both major depression and depression, but in the methods (section 2.2), no
definition on major depression. please describe how depression and major depression in both
NHANES and MR analysis. Please also clarify whether constipation is chronic or transient in
the study. Depression/major depression are chronic from clinical perspective. Please clarify this
as well.
The flow chart for the NHANES analysis is helpful, it would be very helpful to provide flowchart
for the MR analysis given its complexity. For example, how many patients were included from
what database and what were the SNPs included (and excluded) in the analysis, what was the
main analysis, and what were the sensitivity analyses, etc.
The NHANES analysis showed that the association between depression and constipation is valid
among those without vigorous activities. Did the MR analysis take this into consideration? It’s
not mentioned at all.
Results (section 3.2) described a significant nonlinear relationship between depression scores
and risk of constipation. Does this mean both very low and high depression scores are associated
with constipation? Please include some interpretation on this.
The results from MR analysis of depression and constipation are very different from than those
from NHANES analysis: ORs were drastically higher, is this plausible? In contrast, the ORs on
major depression and depression from MR analysis are lower than NHANES analysis. Some
explain would be appreciated.
In the discussion, the authors said that antidepressant medication may alleviate constipation
to explain the weak association in MR analysis. However, some antidepressants can also
increase the risk of constipation. Also, the study excluded those with diarrhea (as described in
the NHANES analysis, not clear in MR analysis), then likely only those who well tolerated
antidepressants (who had no diarrhea) were included in the study, thus the representativeness
of the study population is limited.
“In conclusion, we combined cross-sectional studies from NHANES with bidirectional two-
sample MR analysis”. But it seems that these two analyses were separate: different study
population, and results were not compared or linked somewhat.
Given the above, the conclusion on the causal inference is seeming too assertive. Discussions on
the limitations of the MR analysis in this study would be helpful, for example, potential violation
of assumptions for the methods used (IVW method, MR-Egger, etc).
Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 1 Date: 29 Aug 2024
Reviewer's report:
The study included both major depression and depression, but in the methods (section 2.2), no
definition on major depression. please describe how depression and major depression in both
NHANES and MR analysis. Please also clarify whether constipation is chronic or transient in
the study. Depression/major depression are chronic from clinical perspective. Please clarify this
as well.
The flow chart for the NHANES analysis is helpful, it would be very helpful to provide flowchart
for the MR analysis given its complexity. For example, how many patients were included from
what database and what were the SNPs included (and excluded) in the analysis, what was the
main analysis, and what were the sensitivity analyses, etc.
The NHANES analysis showed that the association between depression and constipation is valid
among those without vigorous activities. Did the MR analysis take this into consideration? It’s
not mentioned at all.
Results (section 3.2) described a significant nonlinear relationship between depression scores
and risk of constipation. Does this mean both very low and high depression scores are associated
with constipation? Please include some interpretation on this.
The results from MR analysis of depression and constipation are very different from than those
from NHANES analysis: ORs were drastically higher, is this plausible? In contrast, the ORs on
major depression and depression from MR analysis are lower than NHANES analysis. Some
explain would be appreciated.
In the discussion, the authors said that antidepressant medication may alleviate constipation
to explain the weak association in MR analysis. However, some antidepressants can also
increase the risk of constipation. Also, the study excluded those with diarrhea (as described in
the NHANES analysis, not clear in MR analysis), then likely only those who well tolerated
antidepressants (who had no diarrhea) were included in the study, thus the representativeness
of the study population is limited.
“In conclusion, we combined cross-sectional studies from NHANES with bidirectional two-
sample MR analysis”. But it seems that these two analyses were separate: different study
population, and results were not compared or linked somewhat.
Given the above, the conclusion on the causal inference is seeming too assertive. Discussions on
the limitations of the MR analysis in this study would be helpful, for example, potential violation
of assumptions for the methods used (IVW method, MR-Egger, etc).
Please review this paper.
user
Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 1 Date: 29 Aug 2024
Reviewer's report:
The study included both major depression and depression, but in the methods (section 2.2), no
definition on major depression. please describe how depression and major depression in both
NHANES and MR analysis. Please also clarify whether constipation is chronic or transient in
the study. Depression/major depression are chronic from clinical perspective. Please clarify this
as well.
The flow chart for the NHANES analysis is helpful, it would be very helpful to provide flowchart
for the MR analysis given its complexity. For example, how many patients were included from
what database and what were the SNPs included (and excluded) in the analysis, what was the
main analysis, and what were the sensitivity analyses, etc.
The NHANES analysis showed that the association between depression and constipation is valid
among those without vigorous activities. Did the MR analysis take this into consideration? It’s
not mentioned at all.
Results (section 3.2) described a significant nonlinear relationship between depression scores
and risk of constipation. Does this mean both very low and high depression scores are associated
with constipation? Please include some interpretation on this.
The results from MR analysis of depression and constipation are very different from than those
from NHANES analysis: ORs were drastically higher, is this plausible? In contrast, the ORs on
major depression and depression from MR analysis are lower than NHANES analysis. Some
explain would be appreciated.
In the discussion, the authors said that antidepressant medication may alleviate constipation
to explain the weak association in MR analysis. However, some antidepressants can also
increase the risk of constipation. Also, the study excluded those with diarrhea (as described in
the NHANES analysis, not clear in MR analysis), then likely only those who well tolerated
antidepressants (who had no diarrhea) were included in the study, thus the representativeness
of the study population is limited.
“In conclusion, we combined cross-sectional studies from NHANES with bidirectional two-
sample MR analysis”. But it seems that these two analyses were separate: different study
population, and results were not compared or linked somewhat.
Given the above, the conclusion on the causal inference is seeming too assertive. Discussions on
the limitations of the MR analysis in this study would be helpful, for example, potential violation
of assumptions for the methods used (IVW method, MR-Egger, etc).
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