PONE-D-23-25155An epidemiological study of season of birth, mental health, and neuroimaging in the UK BiobankPLOS ONE

Dear Dr. Howard,

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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We look forward to receiving your revised manuscript.

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Kenji Tanigaki, 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: Partly

Reviewer #2: Partly

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

Reviewer #1: I Don't Know

Reviewer #2: No

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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: 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: I have read with interest the manuscript by Viejo-Romero et al. on the effect of season of birth on mental health in adults. It is especially relevant the fact that they use a large and high-quality database as the UK Biobank to study this effect, which has received moderate attention in recent years. Authors find small effects relating probable recurrent Major Depressive Disorder with the summer. However they do not find a similar effect with probable hypomania, mania or, importantly, single episode Major Depressive Disorder. Additionally, they find a high number of neuroimaging correlations.

Overall, reporting is of high quality and follows current standards. However, I have some issues with the article as it stands that question the robustness of its results and if solved would probably improve the paper and its addition to the field.

I have to say that I am slightly biased against the hypothesis that authors propose, as I do not think that there is a strong biological basis for any long-last consequences of date of birth. The article does not help against my skepticism of the field. All in all, the authors are not able to convincingly proof whether there is something to be learnt from the current study or it is simply an statistical fluke.

Regarding the neuroimaging data, the relevance of its results is hard to assess. As it is frequent in the neuroimaging literature, some correlations are found without any possibility to judge whether they are relevant or not… I cannot judge this section as one is easily lost in the jungle of measures and RoIs… I would however recommend the authors to include a paragraph on how the FDR correction holds when it is applied to many different comparisons independently.

The models directly linking date of birth and risk of mental health issues are slightly more interpretable. However, they are far from being straightforward. Indeed the phenotypic score for season (“The birth month of each participant was transformed via a cos function, with the lowest phenotypic score (-1) corresponding to those born in December and the highest phenotypic score corresponding to those born in June (+1)”) is only one of multiple parametrizations, which is selected without justification. Even more importantly, associations between the four mental health phenotypes and seasonality were tested using a complex logistic binomial regression analysis in which sex, age, age2, Townsend Deprivation Index, assessment centre attended and place of birth location were included as covariates. There is no description on how authors arrived at the selection of these factors. My suspicion is that the result found may not be robust to changes in the proposed model and may be the result of the “garden of forking paths” and the researcher’s degrees of freedom in their design. The following actions could provide additional confidence in the results:

1-Proof indicating that these choices were carried out a-priori (eg: a public protocol or previous references by the authors or other researchers using the exact same parametrizations and models). If not possible, at least some information on how and why they were selected.

2-A declaration by the authors indicating that this was the only model tested.

3-Some sort of multiverse testing or robustness checks showing how different changes in the analytical decisions affect the results. An easy one would be to show the results of the logistic model with different combinations of the covariates.

In addition to the above, the article as written gives too little weight to the uncertainty present in the results. Some things that could be improved:

1-include in abstract the negative results with the other disorders. If authors need to cut some parts, the imaging info in the abstract could be mostly dropped.

2-Uncertainty of the results should be included, for example in P13-L246, but also other parts of the discussion.

3-Reduce Post-hoc reasoning on why negative results were found: reasons provided for example in p14 l 262 are probably less likely than the elephant in the room (that is, that the positive results found was simply an statistical fluke).

4-Include a section on limitations of the current study, which should include the fact that there is not a good explanation on why results where only found for recurrent MDD.

Reviewer #2: UK Biobank data are used to test the hypothesis that seasonality influences the incidence of affective disorders and brain structural measures derived from MRI. An excess number of diagnoses of recurrent depression is found during the summer months and seasonality is associated with some neuroimaging markers.

Whilst the motivation for the conception and design is broadly sound, the exclusion of non-white participants without any scientific justification, or indeed any justification at all, is unacceptable. Whilst I am in no doubt that the authors hold no ill intentions, funding agencies – including the Wellcome Trust – are absolutely clear that scientific studies should be for the benefit of everyone. Moreover, we are ethically compelled to undertake research for the whole community unless there are specific reasons not to do so. This is particularly relevant here given that in the UK people with Black ethnicity have almost twice the prevalence of depression compared to European (white) ethnicity [doi: 10.1017/S0033291714002967].

The article requires careful reconsideration. The exclusion of any group based on their ethnicity needs strong and credible justification.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-25155R1An epidemiological study of season of birth, mental health, and neuroimaging in the UK BiobankPLOS ONE

Dear Dr. Howard,

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.

Please submit your revised manuscript by Jan 29 2024 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• 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,

Kenji Tanigaki, Ph.D., M.D.

Academic Editor

PLOS ONE

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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: No

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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: While I am still biased against the study results, authors have shown an extreme responsiveness to my comments and have provided as much evidence of the reliability of their results as it was feasible to ask. Hence, I believe that the article in its current form has greatly improved and is suitable for publication. I want to congratulate authors for their effort in their updated version.

Reviewer #2: UKBiobank data were used to investigate seasonality of birth with mental health traits and brain morphology and microstructure measured from MRI. Depressive traits were associated with summer births as were significant increases in cortical thickness. Changes to diffusion measures were associated with winter births.

The scientific reasoning behind this study described in the Introduction is that the season of birth affects brain structure and changes to brain structure are observed in mental health disorders.

The observed effects of seasonality of birth are weak and do not help clarify a confused literature and seasonality of birth effects include some areas that overlap with a recent meta-analysis of cortical thickness in cross-sectional primary literature of (diagnosed) MDD, although the direction is reversed, although the entire cohort is used in the linear model rather than focusing on any particular trait.

A more direct comparison of the underlying hypothesis would be that once seasonality of birth and prevalence is established for, as it would appear, MDD traits, then first undertake a case-control comparison of all participants with MDD traits, and then a MDD traits summer compared to winter births. The expectation would be a pattern of differences similar to that seen in the literature with effect sizes increased in summer compared to winter. Alternatively, apply the linear model to predict brain imaging measures with a main effect of mental health trait and a trait x month interaction, expecting effects in brain regions that match to some extent with the literature.

In short, a credible hypothesis is posited that should be directly addressed by the analysis strategy.

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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

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank

PONE-D-23-25155R2

Dear Dr. Howard,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Kenji Tanigaki, Ph.D., M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #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 #2: Yes

**********

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

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 #2: Yes

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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 #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 #2: (No Response)

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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 #2: Yes: John Suckling

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