Title: Causal Relationship Between Major Depressive Disorder, Anxiety Disorder and
Constipation: A Two-sample Mendelian randomization study
Version: 0 Date: 28 Sep 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a review of the manuscript titled " Causal Relationship
Between Major Depressive Disorder, Anxiety Disorder and Constipation: A Two-sample
Mendelian randomization study" where its authors used Mendelian Randomization (MR)
approach to dissect relationships between MDD, anxiety disorder  and constipation in a
bidirectional way. A significant link between MDD and constipation was found, but not vice
versa. No relationship between anxiety and constipation were found.
I found this to be interesting, well written MS, where i have especially like the Discussion
section, where authors emphasize on action of CRF. Pitifully, two recent papers were published
on the same link of depression and constipation, both done by MR ( PMID: 38973539; PMID:
38806066); authors should acknowledge and discuss these papers. Also, please edit a line
in Abstract : " According to the inverse MR analysis (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1), all the results were negative." Please change to " In the
inverse MR analysis, no causal associations were found (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1)." Also, there is two phrases in Discussion, where word
"prevalence" is found three times in two lines of text. Please edit for word replacement.
REQUESTED REVISIONS:
please see notes above. MS is of good quality.
ADDITIONAL REQUESTS/SUGGESTIONS:
this is a very good quality MS that, unfortunately, is of confirmatory nature
Title: Causal Relationship Between Major Depressive Disorder, Anxiety Disorder and
Constipation: A Two-sample Mendelian randomization study
Version: 0 Date: 28 Sep 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a review of the manuscript titled " Causal Relationship
Between Major Depressive Disorder, Anxiety Disorder and Constipation: A Two-sample
Mendelian randomization study" where its authors used Mendelian Randomization (MR)
approach to dissect relationships between MDD, anxiety disorder  and constipation in a
bidirectional way. A significant link between MDD and constipation was found, but not vice
versa. No relationship between anxiety and constipation were found.
I found this to be interesting, well written MS, where i have especially like the Discussion
section, where authors emphasize on action of CRF. Pitifully, two recent papers were published
on the same link of depression and constipation, both done by MR ( PMID: 38973539; PMID:
38806066); authors should acknowledge and discuss these papers. Also, please edit a line
in Abstract : " According to the inverse MR analysis (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1), all the results were negative." Please change to " In the
inverse MR analysis, no causal associations were found (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1)." Also, there is two phrases in Discussion, where word
"prevalence" is found three times in two lines of text. Please edit for word replacement.
REQUESTED REVISIONS:
please see notes above. MS is of good quality.
ADDITIONAL REQUESTS/SUGGESTIONS:
this is a very good quality MS that, unfortunately, is of confirmatory nature
Please review this paper.
user
Title: Causal Relationship Between Major Depressive Disorder, Anxiety Disorder and
Constipation: A Two-sample Mendelian randomization study
Version: 0 Date: 28 Sep 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is a review of the manuscript titled " Causal Relationship
Between Major Depressive Disorder, Anxiety Disorder and Constipation: A Two-sample
Mendelian randomization study" where its authors used Mendelian Randomization (MR)
approach to dissect relationships between MDD, anxiety disorder  and constipation in a
bidirectional way. A significant link between MDD and constipation was found, but not vice
versa. No relationship between anxiety and constipation were found.
I found this to be interesting, well written MS, where i have especially like the Discussion
section, where authors emphasize on action of CRF. Pitifully, two recent papers were published
on the same link of depression and constipation, both done by MR ( PMID: 38973539; PMID:
38806066); authors should acknowledge and discuss these papers. Also, please edit a line
in Abstract : " According to the inverse MR analysis (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1), all the results were negative." Please change to " In the
inverse MR analysis, no causal associations were found (constipation to MDD: p=9.37×10-1;
constipation to AXD: p=8.51×10-1)." Also, there is two phrases in Discussion, where word
"prevalence" is found three times in two lines of text. Please edit for word replacement.
REQUESTED REVISIONS:
please see notes above. MS is of good quality.
ADDITIONAL REQUESTS/SUGGESTIONS:
this is a very good quality MS that, unfortunately, is of confirmatory nature
assistant