PONE-D-22-16227ALTITUDE AND DEPRESSIVE SYMPTOMS IN THE PERUVIAN POPULATION: ANALYSIS OF A DEMOGRAPHIC AND FAMILY HEALTH SURVEY, 2019PLOS ONE

Dear Dr. Failoc-Rojas,

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Additional Editor Comments:

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ACADEMIC EDITOR: Please consider all reviewers' suggestions.

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study evaluated a potential role of high-altitude living (Peruvian population) on the prevalence of depression symptoms (using the Patient Health Questionnaire, PHQ-9). The authors report an association between living above 1500 m and symptoms of depression and suggest that hypobaric hypoxia may represent one mechanism explaining this association.

The authors deal with an interesting and important issue from a scientific and a clinical perspective as well. Although this is a well-designed and nicely presented study, several points should be addressed before a final recommendation can be made:

First, the authors may a bit more in detail discuss (in the intro section) why high-altitude living (and hypobaric hypoxia) may provoke depression. Based on that it should be possible to state a clear hypothesis. You may consider (beside others) the following reviews: PMID: 29517615, PMID: 35661753).

Further, the procedure of recruitment (and inclusion) of study participants may be better explained (possibly including a figure), e.g., total persons eligible, inclusion, exclusion criteria, number of respondents, etc.

Are you sure that potential inter-correlations between predictors with have been sufficiently considered by your statistical approach?

The increase in depressive symptoms is not much different from 1500-2500 m to > 2500 m. If hypoxia would represent a major explaining mechanism, one would expect an increase of symptoms with altitude.

There are several other environmental factors that could influence depression,

e.g., UV-radiation, temperature, etc., but also life-style factors (like diet, physical activity, alcohol consumption, etc.) and employment status. You may elaborate a bit on that.

In my opinion, your data do not support the conclusion that the higher the altitude the more frequent are depressive symptoms. Please, check and explain.

A more clinically useful approach should be provided how to implement your findings.

Please, do not forget to mention other (here not or less considered) risk factors like social support, sleep quality/duration, physical activity….

Reviewer #2: Dear Authors of the research paper entitled "ALTITUDE AND DEPRESSIVE SYMPTOMS IN THE PERUVIAN POPULATION:

ANALYSIS OF A DEMOGRAPHIC AND FAMILY HEALTH SURVEY, 2019" with pleasure, I have read your work that seeks to determine the importance of hypoxia concerning the possible effects that this may have on depression (and mood). Your work is interesting and the sample is essential. Having said that, I have a few observations that require your review in order to consider this work as suitable for publication.

General. The title is very unspecific and could be more "interesting" to the reader, for example, I suggest ideas: Analysis of the differences in the depression score (PHQ-9) at different altitudes in Peru" or something like that.

The STROBE reporting format is incomplete, there is missing information and I suggest to review step by step the available template.

Third, it seems to me that a work like this could benefit from a figure showing the differences (pictorially) between the different elevations.

The justification in relation to elevation due to lower PO2 would seem to be very theoretical, there is evidence to suggest that elevation is associated with such findings, among them:

about PO2 and envirment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420699/

About suicide at high altitude

https://pubmed.ncbi.nlm.nih.gov/29017474/

About altitude, depression and self-perception

https://pubmed.ncbi.nlm.nih.gov/35020475/

Specific comments

Was the questionnaire conducted in all of Peru? how were the locations classified ? by city altitude ? by canton ? by parishes?

On the other hand, did they use any standard classification about altitude and its ranges? in general there are several classifications (<2,500 m low vs high > 2,500) or the category of low, moderate, high and very high (read this article https://www.frontiersin.org/articles/10.3389/fphys.2021.733928/full )

it is noteworthy that there is less depression above 2500 m and that moderate altitudes have more, so it is essential to categorize the variables on the altitude properly.

In general, the work is interesting, but I think that the observations should be considered to improve the work.

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Reviewer #1: No

Reviewer #2: Yes: Esteban Ortiz-Prado

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PONE-D-22-16227R1Disparities in the prevalence of screened depression at different altitudes in Peru: A retrospective analysis of the ENDES 2019PLOS ONE

Dear Dr. Failoc-Rojas,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR: Consider all of Reviewer 2's points. I ask that you take special care to justify the attitude ranges used in population stratification and strictly follow the STROBE guidelines. Please consider writing more about the pathophysiological mechanisms of the findings, as we believe this will be a publication of great interest to our readers. 

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Please submit your revised manuscript by Dec 11 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Marcus Tolentino Silva

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I appreciate the efforts made by the authors in order to revise their manuscript.

All my points have been considered adequately.

I do not have further comments.

Reviewer #2: Dear authors, thank you for allowing me to review your work entitled "altitude and depressive symptoms in the Peruvian population: analysis of a demographic and family health survey, 2019.

First of all, I would like to congratulate you for bringing to the table such an important issue as the role of the environment, in this case living at high altitudes, on people's health.

Now, once I have reviewed your work, I have many concerns about your manuscript in terms of rigor, that might jeopardize the publication of your work as is, however, I am open to re-consider your work for a future revision if you ammed many of the flaws found within the manuscript.

General comments:

Your paper is not in the correct publication format for this type of study, and you should review the STROBE guidelines and follow each criterion to submit your paper.

Second, their work of revision of the literature is inferior; they have not delved into the subject of the physiopathology of the possible causes behind depression in the inhabitants of high altitudes, nothing is said about the metabolism of serotonin at high altitudes, the role of neurodevelopment is not mentioned, there is no mention of self-perception at high altitude, suicide rates at high altitudes use US data (which has almost no populations living at high altitude) and so on (refeer to the literature for further information https://pubmed.ncbi.nlm.nih.gov/35020475/

Third, the altitude ranges are arbitrary; why do they use that range? Where do they get it from? The altitude ranges have been described previously and are well known among those who do high altitude medicine, they can use the simple range of low and high altitude (< or > 2,500 m) or the range of low (<1500), moderate (1500-2500), high altitude (2500-3500) and very high altitude (3,500 to 4300 m) see the following work for further detail https://pubmed.ncbi.nlm.nih.gov/34675818/

If you cannot analyze the results with those altitude ranges, it is difficult for me to accept it for publication unless you have a substantiated and factual response. Now the statistical analysis is adequate, even though it excludes essential factors such as the length of residence of the highlanders, they were born at high altitudes or they only live at higher altitudes. What about the discussion around culture, why not comparing indigenous people of low altitudes with those indigenouse people at high altitudes, i.e., you can analyze proportions between low versus high, but among the same ethnic group, are there differences?

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Reviewer #1: Yes: Martin Burtscher

Reviewer #2: Yes: Esteban Ortiz-Prado

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Disparities in the prevalence of screened depression at different altitudes in Peru: A retrospective analysis of the ENDES 2019

PONE-D-22-16227R2

Dear Dr. Failoc-Rojas,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Marcus Tolentino Silva

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you.

The authors have already addressed adequately all my comments in revision 1.

I do not have further comments.

Reviewer #2: Dear Authors, the work is much better in this version. The changes are positive. I am still not convinced about the height ranges, and although other people have used them, that does not mean that they are the most recognized, in short, the additional analysis contributes to improving the quality of the work. For the rest, I think the work is fine, I would improve the forest plot somewhat; although the title is good in the graph, it does not sound good, maybe explain it in the title of the figure. For the rest, I have no more comments

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Reviewer #1: Yes: Martin Burtscher

Reviewer #2: Yes: Esteban Ortiz-Prado

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