PONE-D-19-27517

Predictors of a first recurrence of major depressive disorder

PLOS ONE

Dear Professor Lye,

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Kind regards,

Zezhi Li, Ph.D., M.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

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: Yes

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: Yes

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3. 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: Yes

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4. 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: No

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: The authors want to identify the predictive factors for recurrence of major depressive disorders in 5-year follow-up study. They found that the social avoidance and severity of previous MDD could predict the recurrence, with 287 ApaI +64978C>A genotypes acting in synergy with severity in potentiating the risk of recurrence. It is an interesting paper, but some concerns should be addressed.

In the abstract

1. The aim of the present study should be presented.

2. “201 cases of major depressive disorder from four public hospitals in Malaysia were traced over a 5-year period from 2014 to 2017”. It should be “A total of 201 patients with major depressive disorder from four hospitals in Malaysia were followed up for 5 year”. Case should be revised as “patients” throughout the paper.

In the introduction

3. The definition of “recurrence” should cite the reference.

In the methods

4. Please clarify the inclusion and exclusion criteria for recruiting the patients.

5. Please detail the methods of DNA extraction.

6. Why the authors selected the SNPs of Vitamin D Receptor, Zinc Transporter-3, Dopamine Transporter-1, Brain-derived Neurotropic Factor, Serotonin Receptor 1A and 2A?

7. Why the author selected the variables with p values less than 0.25 from the Kaplan-Meier results, for the next Cox regression model?

In the discussion

8. The author should discuss the limitation of this study, such as the moderate sample size.

9. Overall, the language of the study should be improved, and the paper should be revised carefully.

Reviewer #2: Thank you for the opportunity to submit this manuscript. The information that Social avoidance and vitamin D receptor were prognostic of recurrence of major depressive disorder was very helpful. However, I still have several comments. I also think that some more discussion is warranted. In its current shape I am not fully convinced if this manuscript is ready to be published.

1.I don’t think that paragraph 1 with so much words is essential, considering the major aims of this manuscript.

2.I would suggest that more should be added to paragraph 3 (line 73 to 76 ) in introduction section considering the major findings of this manuscript.

3.Just as the author stated in Introduction section that those of younger age, women and family history of MDD were at higher risk of recurrence. However these findings were not consist with results of this manuscript. Readers would have great interest on the discussion of this part.

4.I would suggest that limitations should be listed in discussion section.

5.It is interesting that the interaction of ApaI +64978C>A genotype with severity at first MDE would predicted the recurrence of MDE. It would be better if more discussion about potential mechanisms added to this part(line 269 to 276) , instead of listing the result.

6.It would be better if more references from the past 5 years are added.

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Reviewer #1: No

Reviewer #2: No

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Predictors of recurrence of major depressive disorder

PONE-D-19-27517R1

Dear Dr. Lye,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Zezhi Li, Ph.D., M.D.

Academic Editor

PLOS ONE

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: 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

**********

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: Yes

**********

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

**********

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: (No Response)

Reviewer #2: It has clearly improved, although better it can be.I would suggest that the edior could consider to publish this manuscript .

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No