-->PONE-D-25-65436-->-->Factors associated with the occurrence and persistence of subthreshold and full attention-deficit hyperactivity disorder in women: a population-based epidemiological study-->-->PLOS One

Dear Dr. Ajdacic-Gross,

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.

Kind regards,

Mu-Hong Chen, M.D., Ph.D.

Academic Editor

PLOS One

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“The CoLaus|PsyCoLaus study (represented by MP) is supported by research grants from GlaxoSmithKline (www.gsk.com), the Faculty of Biology and Medicine of the University of Lausanne (https://www.unil.ch/fbm/en/home/menuinst/faculte.html), and the Swiss National Science Foundation (www.snf.ch) (grants 3200B0–105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535 and 3247730_204523) and the Swiss Personalized Health Network (sphn.ch) (grant 2018DRI01).”

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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: No

Reviewer #3: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: No

Reviewer #3: 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

Reviewer #3: No

**********

-->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: No

Reviewer #3: 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: I have read the above manuscript and give hereafter my comments:

This study covers an interesting issue, yet several aspects are successively described with a neither convincing nor very clear frame.

1. The major concern would be the confounding factors including the psychiatry comorbidities as well as medications seemed not take into consideration of the analyses, especially when analyzed the risk factors of persistent ADHD.

Reviewer #2: This study included a broad range of factors, including family psychiatric comorbidity factors, parental bonding, childhood maltreatment, physical health indicators into analysis to differentiate women with subthreshold and full ADHD. As the authors described, some of these factors were defined as the risk factors and some as “associated” factors. I did not see the hypothesis accounting for the analysis. Further, these were a small number of women having subthreshold or full ADHD. This is far too different from the real-world situation.

Reviewer #3: This study investigated risk factors associated with different subgroups of ADHD in women ADHD, using data from a large Swiss population-based epidemiological cohort. The authors examined a broad range of psychosocial (e.g. adverse childhood experiences, parental bonding), as well as biological and physiological indicators (e.g. childhood infections, cardiometabolic and immunological markers). Overall, this is a data-rich study that addresses an important gap in the ADHD literature, particularly with respect to women and ADHD heterogeneity. The strengths of this manuscript are the large, well-characterized population-based sample, its good representativeness and the richness and breadth of indicators considered. Although some indices are necessarily limited to early-life experiences, the overall multidimensional coverage is impressive. The use of latent class analysis to identify subgroups within subthreshold and full ADHD is a notable contribution, highlighting the substantial heterogeneity of ADHD presentations among women. Overall, I consider this manuscript to be important and novel. My comments below are minor and intended to improve clarity and interpretability.

My primary concern is that the study is highly exploratory and data-driven. This is understandable given the analyses rely on a large, pre-existing epidemiological cohort with a wide array of available measures. However, the manuscript would benefit from a more explicit integrative model of heuristic framework. In particular, the authors could strengthen the discussion by addressing how their findings might translate into practical implication, such as early identification of women at higher risk for persistent ADHD, stratification of ADHD subtypes for prognosis, or potential targets for early intervention.

Minor comments

1. The selection of markers for LCA/LPA was based on a significance threshold p<0.1 for associations with ADHD. The rationale for this decision is unclear and should be more explicitly justified.

2. Table 2. It is unclear why for the same indicator, the total n differs between the subthreshold ADHD group and the full group.

3. When reporting statistics, it would be preferable to report the relevant test statistics (e.g. t value and degrees of freedom), not only the p value (e.g. Line 448), to improve transparency.

4. Line 515 Please check whether the “ACE high BP” group corresponds to Class 3

5. Line 762 The discussion that “lower blood pressure may reflect a distinct subtype of subthreshold ADHD” is intriguing. The authors might consider whether this pattern could relate to concepts such as Cognitive Disengagement Syndrome (or sluggish Cognitive Tempo), autonomic hypoarousal, or alternative neurobiological profiles.

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-->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

Reviewer #3: No

**********

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->PONE-D-25-65436R1-->-->Factors associated with the occurrence and persistence of subthreshold and full attention-deficit hyperactivity disorder in women: a population-based epidemiological study-->-->PLOS One

Dear Dr. Ajdacic-Gross,

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 Apr 22 2026 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 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,

Mu-Hong Chen, M.D., Ph.D.

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

-->Please optimal answer the reviewer's comment:-->-->

1. The major concern would be the confounding factors including the psychiatry comorbidities as well as medications seemed not take into consideration of the analyses, especially when analyzed the risk factors of persistent ADHD.
2. The authors partially replied to my comment about the confounding factors, including comorbidities and medications. They plan to conduct further analysis about the comorbidities in the future. The authors also argued that medication plays a comparatively minor role in this cohort because pharmacological treatment for ADHD was not available to the majority of participants during their developmental years, young and middle adulthood (median birth year 1952/1953). However, data shows that the FDA has approved Methylphenidate (MPH) for ADHD treatment as early as early 1960s. Therefore the concern about confounding factors still existed.

-->

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

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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

-->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: Partly

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

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

Reviewer #1: No

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

-->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: No

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

-->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: (No Response)

Reviewer #3: (No Response)

**********

-->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: The authors partially replied to my comment about the confounding factors, including comorbidities and medications. They plan to conduct further analysis about the comorbidities in the future. The authors also argued that medication plays a comparatively minor role in this cohort because pharmacological treatment for ADHD was not available to the majority of participants during their developmental years, young and middle adulthood (median birth year 1952/1953). However, data shows that the FDA has approved Methylphenidate (MPH) for ADHD treatment as early as early 1960s. Therefore the concern about confounding factors still existed.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

-->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: Yes: Cheng-Fang Yen

Reviewer #3: 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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Factors associated with the occurrence and persistence of subthreshold and full attention-deficit hyperactivity disorder in women: a population-based epidemiological study

PONE-D-25-65436R2

Dear Dr. Vladeta Ajdacic-Gross,

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,

Mu-Hong Chen, M.D., Ph.D.

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments: