Peer Review History

Original SubmissionMay 16, 2022
Decision Letter - Jerritta Selvaraj, Editor

PONE-D-22-14224Connective differences between autism spectrum disorder with depressive state and depression: case-control study.PLOS ONE

Dear Dr. Kaneko,

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 Nov 07 2022 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,

Jerritta Selvaraj

Academic Editor

PLOS ONE

Journal Requirements:

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

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"No financial disclosure."

At this time, please address the following queries:

a)        Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

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Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

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We will update your Data Availability statement to reflect the information you provide in your cover letter.

5. 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.

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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: Partly

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

Reviewer #1: I Don't Know

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: No

Reviewer #2: No

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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: a) the manuscript can provide further more information regarding the Autism Spectrum Disorder with depressive state and with depression for clarity of the topic and need to do the research. the reviewer wasn't able to capture the clear information regarding the ASD with depressive state and depression. it is understood from science that brain structural differences are seen in persons with ASD and without ASD and this needs to correlated as the study is done with the help of MRI.

b) as far as ASD condition is concerned, the males are more affected by ASD than females. the article should have pronounced sex differences, since females experience twice as much depression as males.

c) As a Rehabilitation Professional- Educationists , Psychologists look for the behavioural output of the subjects. it is not revealed in the study and the reviewer has limitations in further reviewing the manuscript.

Reviewer #2: Title: Connective differences between autism spectrum disorder with depressive state and depression: case-control study

1. How the authors describe the resting state of ASD individuals? Since the people with ASD has different comorbidities and exhibit restlessness in some individuals,

2. Authors pls check for the abbreviations for eg:-DSM 5 is repeated .It can be defined at initial stage itself.

3. Methodology can be given in detail using a block diagram or pictorial representation

4. Technical information is lagging in the manuscript. Such as pre-processed images its metrics and equation related to filtering

5. There is no proof for pre-processing of the functional and structural images and the metrics can be specified.

6. Did the ASD participants were assisted by their caregivers?

7. ASD individuals don’t adjust to social setting. Pls mention the challenges in recording rs fMRI

8. Figure 1 and 2 can be cited with more information.

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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: Yes: B. Anandhi

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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.

Attachments
Attachment
Submitted filename: Connective Diff-Comments.docx
Revision 1

Reviewer #1: a) the manuscript can provide further more information regarding the Autism Spectrum Disorder with depressive state and with depression for clarity of the topic and need to do the research. the reviewer wasn't able to capture the clear information regarding the ASD with depressive state and depression. it is understood from science that brain structural differences are seen in persons with ASD and without ASD and this needs to correlated as the study is done with the help of MRI.

Response: We thank the reviewer for this comment. In response, we have performed voxel-based morphometry and added the following sentences to the Methods, Results, and Discussion sections.

Methods

“Structural analysis

Voxel-based Morphometry

We used SPM12 to estimate differences between depression and ASD with depressive state. Preprocessed structural images were smoothed with a 6-mm Gaussian kernel of FWHM to increase the S/N ratio.

Post-processed structural images were divided into two groups: ASD with depressive state and depression. First, we constructed a design matrix to adopt the general linear model (GLM) and identify regions significantly related to the differences between the two groups. We also performed estimation to validate the independently distributed residuals. Finally, we analyzed the two-sample t-test using the standard parametric procedure to test the hypothesis.[21]”

Results

“Volumetric findings

There was no significant difference between ASD with depressive state and depression.”

Discussion

“We performed voxel-based morphometry using SPM12 to compare the structural differences between ASD and depression.[21] Our results showed no significant structural differences between these two groups, although previous studies demonstrated variable structural abnormality in ASD subjects presenting with increased and decreased volumes in specific areas of the brain.[36-39] ASD subjects in previous studies varied in both age and clinical background (comorbidity, educational and genetic profiles). Compared with healthy controls adult ASD subjects, Ecker et al showed that adult ASD subjects had increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and decreased volume in the occipital and medial parietal regions, despite there being no significant difference in whole brain volume.[36] In the present study, ASD subjects showed no structural differences compared to subjects with depression. However, subjects with depression were known to display significant volume reductions compared to healthy controls, especially in the hippocampus and amygdala.[40-41] We assumed that the differences in morphological alterations in each study could be due to differences in clinical background. Therefore, our results indicated some structural abnormality in ASD subjects that should be reexamined in healthy controls.”

b) as far as ASD condition is concerned, the males are more affected by ASD than females. the article should have pronounced sex differences, since females experience twice as much depression as males.

Response: We thank the reviewer for this comment. We added following paragraphs in the Discussion section.

“In this study, the numbers of male and female subjects were equal in both the groups. Although there were slightly more male subjects with ASD and slightly fewer male subjects with depression, there was no statistically significant difference in gender distribution. In general, ASD is more than 4 times more common among males than among females, and depression is twice as common among females.[22-24] The equal number of males and females in this study was considered to match that in a previous study because of the opposite gender distribution between ASD and depression. However, the sample size in this study was too small to analyze gender differences. In the case that no gender differences were found in the population presenting with depression, other psychiatric disorders may need to be considered.”

c) As a Rehabilitation Professional-Educationists, Psychologists look for the behavioural output of the subjects. it is not revealed in the study and the reviewer has limitations in further reviewing the manuscript.

Response: We thank the reviewer for this comment. At our institution, patients referred from other institutions are examined, psychologically tested, and diagnosed clinically by an experienced psychiatrist. In this study, patients showed symptoms of depressive state, as shown in the inclusion criteria. However, subsequent physical examination and psychological testing revealed that the depressive state was associated with ASD rather than depression. Many patients received rehabilitation and treatment at the referral institution after the diagnosis was made. It was therefore difficult to consider outputs in more detail. We would appreciate the reviewer’s understanding on this matter.

Reviewer #2: Title: Connective differences between autism spectrum disorder with depressive state and depression: case-control study

1. How the authors describe the resting state of ASD individuals? Since the people with ASD has different comorbidities and exhibit restlessness in some individuals,

6. Did the ASD participants were assisted by their caregivers?

7. ASD individuals don’t adjust to social setting. Pls mention the challenges in recording rs fMRI

Response: We thank the reviewer for this comment. As pointed out, MRI examinations are considered difficult for patients with ASD, ADHD, and PDD, and ASD was reviewed. All participants in this valuable review were under 20 years of age, and most were children around 10 years of age. In contrast, our target patients were aged over 20 years and were willing to participate in this MRI study. In addition, he presented to the hospital in a depressed state, which is also considered to be the reason why there was no interruption due to movement during the examination and no deterioration of the image. All patients did not require caregiver attendance. However, as the reviewer pointed out, testing is expected to be difficult in general; we would therefore like to state in the Discussion section that the subject in this case was biased toward ASD who showed depressive state. We have revised the relevant paragraphs in Methods and Discussion sections according to these comments.

2. Authors pls check for the abbreviations for eg:-DSM 5 is repeated .It can be defined at initial stage itself.

Response: We thank the reviewer for this comment. We have modified the manuscript accordingly.

3. Methodology can be given in detail using a block diagram or pictorial representation

4. Technical information is lagging in the manuscript. Such as pre-processed images its metrics and equation related to filtering

5. There is no proof for pre-processing of the functional and structural images and the metrics can be specified.

Response: We thank the reviewer pointing this out. We added details on preprocessing accordingly. In addition, we created a block diagram explaining the processing method conducted in our study. Regarding the metrics, we did not add a corresponding diagram and explanation because they are described on the relevant web page.

8. Figure 1 and 2 can be cited with more information.

Response: We thank the reviewer for this comment. We have inserted the necessary citations in the figures accordingly.

Attachments
Attachment
Submitted filename: revise_comment_to_reviewer_revise.docx
Decision Letter - Federico Giove, Editor

PONE-D-22-14224R1Connective differences between autism spectrum disorder with depressive state and depression: case-control study.PLOS ONE

Dear Dr. Kaneko,

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.

Reviewer #2 raised a number of further issues. Authors are encouraged to evaluate if amending the manuscript according to reviewer suggestions. Please include a rebuttal letter detailing which concerns have been addressed (and how), and which concerns have not been addressed (and why). Note that I'm not implying that all the concerns must be addressed. I'll take a final decision without further reviewers involvement.

Please submit your revised manuscript by Jun 29 2023 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,

Federico Giove, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[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 #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 #2: Partly

**********

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

Reviewer #2: N/A

**********

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: No

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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: No

**********

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: Dear Authors,

1.Authors pls expalin what is the dfifference between depressive state and depression.? Does the authors trying to find out mild , moderate or severe level of depression?

2.The authors have mentioned the preprocessing methods such as slicing, band pass filtering, smoothing and normalization but there is axial information of the filtered image , sliced image or normalized image ?Probably you can tabulate the results of each step and its S/N ratios achieved.

3.Though you use CONN connectivity tool box , need to mention the actual analysis between depressive state and depression this analysis. Pls give the raw image of Depression and Depressive state image

4 Authors claim that the statistical analysis by performing the F test, has right supramarginal gyrus (SMG) (p-FDR < 0.04*) and decreased connectivity to the left hippocampus (p-FDR < 0.02*) and para-hippocampus (p-FDR < 0.02*). What tool is used for this test ?.What are the hypothesis? Pls mention the Mean , STD from the statistical analysis.

5.Pls check the entire manusript for phraseaology, grammar ,and the connectivity between each section.

6.Improve the discussion section

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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: Dr.B.Anandhi

**********

[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.

Revision 2

There is no request needed.

Attachments
Attachment
Submitted filename: reply_to_author__wo_ja.docx
Decision Letter - Federico Giove, Editor

PONE-D-22-14224R2Connective differences between patients with depression with and without ASD : a case-control studyPLOS ONE

Dear Dr. Kaneko,

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.

The manuscript is fine, it can be accepted from a scientific standpoint. The data access policy stated in the manuscript is not acceptable. Authors must report in the article text the same policy declared in the forms, and in particular name and email of the person to be contacted to get access to the data. Please note that, even after including these details in the manuscript, the policy of your institution is too restrictive and incompatible with open data principles. For the future, if authors plan to submit to journals that require open data, ethical consent and local policies must be amended to allow unconditional sharing of anonymized data.

Please submit your revised manuscript by Aug 26 2023 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,

Federico Giove, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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

Reviewers' comments:

[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.

Revision 3

Journal Requirements:

1. The manuscript is fine, it can be accepted from a scientific standpoint.

The data access policy stated in the manuscript is not acceptable. Authors must report in the article text the same policy declared in the forms, and in particular name and email of the person to be contacted to get access to the data.

Response: Thank you for reviewing my manuscript.

We have changed our data access policy in the manuscript to be fit in the form.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Response: We have added "doi" to the No. 35 reference. In addition, we changed the style of No. 36 to that of the Book.

There were no comment from reviewer. So, we have submitted a revised version of the paper we submitted on July 9.

Attachments
Attachment
Submitted filename: reply_to_author_wo_ja_0717.docx
Decision Letter - Federico Giove, Editor

Connective differences between patients with depression with and without ASD : a case-control study

PONE-D-22-14224R3

Dear Dr. Kaneko,

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.

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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,

Federico Giove, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Federico Giove, Editor

PONE-D-22-14224R3

Connective differences between patients with depression with and without ASD : a case-control study

Dear Dr. Kaneko:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Federico Giove

Academic Editor

PLOS ONE

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