PONE-D-24-56380Relationship between the ratio of serum uric acid to high density lipoprotein cholesterol and depressive symptoms in middle-aged and elderly ChinesePLOS ONE

Dear Dr. xu,

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 Mar 01 2025 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,

Vinod Kumar Yata, PhD

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1.  Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf   and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.919430/full

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

3. Thank you for stating the following financial disclosure:

“This study was supported by the National Natural Science Foundation of China (Grant No. 82000390) and the Youth Science Foundation Project (Grant No. 81100121).”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

[Note: HTML markup is below. Please do not edit.]

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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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

**********

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: Upon reviewing this manuscript, a primary concern arises, regarding the scientific value of using UHR as a marker for depression, given its primary establishment in previous studies as a predictor of metabolic syndrome (MS). This raises a fundamental "chicken-and-egg" dilemma: MS has been strongly implicated as both a potential cause and a consequence of depression, owing to shared mechanisms such as chronic inflammation, oxidative stress, and insulin resistance. Without addressing this bidirectional relationship, the rationale for UHR serving as an independent marker of depression remains unclear. It would strengthen the manuscript to discuss how UHR might uniquely capture depression-related metabolic dysregulation beyond its established role in MS prediction.

Nevertheless, this manuscript provides a valuable contribution to the field by exploring the novel relationship between UHR and depression, particularly leveraging a robust dataset of over 10,000 participants (However, this is 2011 CHARLS database, which might not entirely reflect current trends or health profiles). The large sample size enhances the statistical power and generalizability of the findings, offering meaningful insights into the potential role of UHR as a biomarker for depression in middle-aged and elderly populations. This study also lays a foundation for future research to elucidate further the mechanistic links between metabolic dysregulation and mental health outcomes.

This manuscript requires substantial revisions to address several critical deficiencies if it is to be accepted. Among the most significant issues are the following (please also refer to comments in the manuscript (PDF):

1. The cross-sectional design limits the ability to infer causal relationships between UHR and depressive symptoms. This limitation is acknowledged but could benefit from further elaboration on its implications and the necessity of longitudinal studies.

2. While many confounders were adjusted for, there might be unmeasured or residual confounders that influence the results, such as dietary habits or physical activity.

3. The manuscript mentions excluding subjects with missing key variable data. This might lead to selection bias, which should be addressed in the discussion.

4. While the quartile analysis is insightful, the rationale for the specific quartile cutoffs could be better explained.

5. The interaction effects in subgroup analyses were explored, but the manuscript lacks a robust discussion of these interactions' clinical or biological significance.

6. It is quite hard to follow the table's presentation. The tables are informative but overwhelming because all data are in table forms. Adding figures (e.g. plots, etc.) to represent the relationship between UHR and depressive symptoms visually could enhance the understanding of key findings.

7. Overgeneralization that UHR could serve as a "potential biomarker for assessing depression risk" might be premature without further validation in diverse populations or experimental studies (this is not well captured in the limitation of the study).

8. In the discussion, while some plausible mechanisms are discussed, they rely heavily on secondary sources. Further emphasis on how UHR directly interacts with pathways involved in depression would strengthen the argument.

9. Certain manuscript parts have redundant statements, particularly in the discussion. These could be streamlined to improve readability. The introduction requires further refinement to enhance the clarity and focus of the study.

10. While the study explores a novel association, the justification for using UHR over other established metabolic markers for depression risk is not convincingly argued. Expanding on why UHR is superior or complementary would enhance its scientific contribution.

Reviewer #2: The title could be improved by changing relationship into association as its the main topic of investigation.

Abstract needs concluding statement for proper justification.

The rationale for choosing UHR over traditional metabolic syndrome markers could be expanded.

The study uses cross-sectional data but does not sufficiently acknowledge its limitation in establishing causation.

Explicitly mention that causation cannot be inferred and suggest longitudinal studies for future research.

The use of a CESD-10 cutoff of ≥10 to define depression should be referenced with relevant studies which is not enough with the provided references.

It is unclear whether all potential confounders were adequately controlled in the regression models.

The study mentions interaction tests but does not explain how they were performed or interpreted.

**********

6. 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

**********

[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.

Attachments

Attachment

Submitted filename: PONE-D-24-56380_reviewer 23.12.2024.pdf

Association between the ratio of serum uric acid to high density lipoprotein cholesterol and depressive symptoms in middle-aged and elderly Chinese

PONE-D-24-56380R1

Dear Dr. xu,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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,

Vinod Kumar Yata, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: