PONE-D-23-07288Structural aging of human neurons is opposite of the changes in schizophreniaPLOS ONE

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Comments to the Author

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

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Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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

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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: The referee has followed the nanoCT papers of brain tissue from this group for some time. The data in the present manuscript represent a very large amount of additional work. The referee recommends that the present paper be accepted after so small improvements are made.

The referee is not a brain researcher and cannot comment, therefore, on the literature cited in the Introduction and Discussion. The x-ray imaging will absolutely solid, in the referee’s opinion.

The Results explain the data concisely but clearly. The details are given in the Supplementary Tables, and all of the samples appear in the main figures or the supplementary figures. Thus, reporting is thorough.

In the Discussion, the authors write (lines 335-339) “Although a methodology to manipulate neuron structure of a specific brain area is currently unavailable, neurite curvature can be used as a hallmark with which to exploit antipsychotics or other interventions that can moderate hallucinations.” This is clumsy, in the referee’s opinion, because the first clause says we cannot change neuron structure and the second part of the sentence sounds like neurite curvature is a hallmark with which to exploit antipsychotics…, which cannot be correct because this brain tissue is only available post mortem. The referee is not at all sure what is meant, and this portion of the Discussion must be clear.

The referee was unclear about the designations: “S7A, S7B, S7C…”. This needs to explicitly clarified. Designators S and N clearly refer to diseased and normal tissue. The 7 must be individual 7, one guesses. Does the last letter indicate different portions of tissue from the individual (here #7)?

Minor point: S2 Table lists pixel sizes. One presumes these are actually the reconstructed volume element (voxel) sizes. If so, this should be changed because pixels are 2D features.

Reviewer #2: Dear Authors,

Thanks for your work.

There are a few comments about this work.

1. The introduction does not contain a clear statement of the purpose of the study. The introduction contains an indication of the results that you are yet planning to present here.

2. The description of the norm group is insufficient. There is no indication of what diseases the subjects suffered. It is not excluded the influence of these diseases on the brain.

3. It is necessary to justify the choice of t-test for statistical analysis.

4. In the Discussion section, the wording is questionable: "Cognitive functions in schizophrenia do not worsen over time." The authors provide references to older publications.

5. You need to add a Conclusions section.

6. It is necessary to transfer the information from the Discussion section to the special section "Restrictions of the study".

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Reviewer #1: Yes: Stuart R. Stock

Reviewer #2: No

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Structural aging of human neurons is opposite of the changes in schizophrenia

PONE-D-23-07288R1

Dear Dr. Mizutani,

Hi - I’d just ask the authors to (1) change “opposite” to another synonym and (2) refine eligibility criteria, like the use of meds, BDNF and other factors that weren’t assessed etc.

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,

Thiago P. Fernandes, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for your thoughtful and careful edits.

Wishing you success with the study.

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

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

Reviewer #1: I Don't Know

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: (No Response)

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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: Accept. The authors have addressed the points this referee raised. They also seem to have covered the points raised by the other referee.

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 #1: Yes: Stuart R. Stock

Reviewer #2: No

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