Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder–an exploratory study

Gloria-Beatrice Wintermann; René Noack; Susann Steudte-Schmiedgen; Kerstin Weidner

doi:10.1371/journal.pone.0273413

Peer Review History

Original SubmissionFebruary 28, 2022
28 Feb 2022 Author Response Attachments Attachment Submitted filename: Reply_Wintermann.docx https://doi.org/10.1371/journal.pone.0273413.r001
4 May 2022 Decision Letter - Walid Kamal Abdelbasset, Editor PONE-D-22-01757Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in Panic Disorder – an exploratory studyPLOS ONE Dear Dr. Wintermann, 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 Jun 18 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, Walid Kamal Abdelbasset, Ph.D. 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. Thank you for stating the following financial disclosure: The present study was funded by the Robert-Pfleger-Stiftung. GBW received the award. 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. 3. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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: 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: 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: The statistical analysis of the study was well thought out and the ANCOVA approach was executed with the limited sample size. Obviously a larger study is needed with up front power calculations and specifically stated objectives. The authors do note that future studies should compare the impact of different intensities of interoceptive exposures, like light vs. moderate or intensive exercise, e.g. using a randomized controlled trial. The investigators gave an honest assessment of the limitations of this study and noted that the present results should be critically reviewed in the context of methodological shortcomings. The sample was not exactly equally paralleled with respect to age and sex. The sample size was quite small with little power, although they do note that a test power of about 34% could be reached when a medium effect size of .25 was supposed (when ANCOVAs were calculated). The present study obviously may be rather evaluated to be a pilot or exploratory study as they note. The descriptive presentation is certainly informative. The investigators should also note with the multiple statistical tests being performed in this limited sample that no adjustment to the p-value has been made for multiple testing and thus the p-values should be interpreted with caution. Reviewer #2: The study titled (Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in Panic Disorder – an exploratory study) is a clinically important one and nicely presented. I have some recommendations: 1- The title: should be "therapeutic" not "therapy" 2- Methods in general lack references in all parts, this is a point of weakness 3- Check if unnecessary abbreviations are not needed ****** 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:** Sawsan Zaitone [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. https://doi.org/10.1371/journal.pone.0273413.r002
Revision 1
23 Jun 2022 Author Response PONE-D-22-01757 Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in Panic Disorder – an exploratory study PLOS ONE Dear Dr. Walid Kamal Abdelbasset , Dear editors, thank you for your interest in our manuscript entitled „Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in panic disorder – an exploratory study“. We have adhered to your and the reviewers´ inquiries and revised our manuscript accordingly. Please find our point-by-point replies (marked yellow) in the following rebuttel letter. All further changes in the manuscript are coloured in yellow as well. Please do not hesitate to contact me in case of further inquiries. Sincerely Yours, Gloria Wintermann (on behalf of all co-authors) Dear Dr. Wintermann, 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 Jun 18 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'. We have attached the document 'Response to Reviewers' accordingly. • 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'. We have attached the document 'Revised Manuscript with Track Changes‘ according to your request. • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. We have attached the document 'Manuscript‘ according to your request. 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 have decided to allow public access to the study protocol and anonymous research data using the Open Science Framework (OSF) https://osf.io/. Access is available using the link: https://osf.io/s76rw/ and https://archive.org/details/osf-registrations-s76rw-v1 The OSF registration doi is the following: 10.17605/OSF.IO/S76RW We look forward to receiving your revised manuscript. Kind regards, Walid Kamal Abdelbasset, Ph.D. 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 Thank you for this hint. We have adapted the file naming accordingly- both in the text and in the attachments. 2. Thank you for stating the following financial disclosure: The present study was funded by the Robert-Pfleger-Stiftung. GBW received the award. 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. Please at the financial disclosure as the following statement: Disclosure „The author reports no conflicts of interest in this work. The present study was funded by the Robert-Pfleger-Stiftung. GBW received the award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.“ 3. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option. The corresponding author Gloria-Beatrice Wintermann is affiliated with the chosen institute. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [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: Partly Reviewer #2: Yes We have now deposited raw data and supporting information such as the study protocol to a public repository. This will allow to better understand the study design and reproduce the study results. ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ________________________________________ 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: No The study data and further supporting information (the study protocol) are available at a public repository called Open Science Framework (OSF) (see above). The relevant links are the following: https://osf.io/. https://osf.io/s76rw/ https://archive.org/details/osf-registrations-s76rw-v1 10.17605/OSF.IO/S76RW All further information needed are available upon request. ________________________________________ 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 ________________________________________ 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 statistical analysis of the study was well thought out and the ANCOVA approach was executed with the limited sample size. Obviously a larger study is needed with up front power calculations and specifically stated objectives. The authors do note that future studies should compare the impact of different intensities of interoceptive exposures, like light vs. moderate or intensive exercise, e.g. using a randomized controlled trial. In lines 147-151 we stated the sample size calculation. Study objectives are included on page 4, lines 91-92, page 5, lines 93-94. We also stated that the present study was realized exploratory a spart of another study (see page 5, lines 101-103). The investigators gave an honest assessment of the limitations of this study and noted that the present results should be critically reviewed in the context of methodological shortcomings. The sample was not exactly equally paralleled with respect to age and sex. The sample size was quite small with little power, although they do note that a test power of about 34% could be reached when a medium effect size of .25 was supposed (when ANCOVAs were calculated). The present study obviously may be rather evaluated to be a pilot or exploratory study as they note. The descriptive presentation is certainly informative. The investigators should also note with the multiple statistical tests being performed in this limited sample that no adjustment to the p-value has been made for multiple testing and thus the p-values should be interpreted with caution. We included a statement that Bonferroni-corrections of p-values were applied where appropriate (see page 11, line 248/ 249). Significance at Bonferroni-adjusted p-value was indicated in the footnote of Table 2 (page 16). Reviewer #2: The study titled (Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in Panic Disorder – an exploratory study) is a clinically important one and nicely presented. I have some recommendations: 1- The title: should be "therapeutic" not "therapy" We have decided to let the title as it is because the term ‚cognitive-behavioral therapy‘ is well-known by the scientific community in this field. We would be glad if you agreed. 2- Methods in general lack references in all parts, this is a point of weakness Thank you for this hint. We have added lacking references (e.g. for the SCID interview, DSM-IV) and referenced studies the methods applied in the present study were based on (e.g. page 7, lines 141, 143). 3- Check if unnecessary abbreviations are not needed. For economic reasons, we decided to use the abbreviations because. After introducing them, they were well-defined for the readership (e.g. page 7, line 143). We have prepared a list of abbreviations and included it in the supporting information for better understanding the abbreviations (see supporting information S5 File). Furthermore, we omitted any confusing abbreviations, e.g. SAM, which we have formerly used for both Sympathetic-Adreno-Medullar and Self-Assessment Manikins. In the revised version we decided to use the full-term Self-Assessment Manikins (e.g. see Table 1). ________________________________________ 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: Sawsan Zaitone [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. Figures have been checked according to the tool you suggested (https://pacev2.apexcovantage.com/ ). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0273413.r003
4 Jul 2022 Decision Letter - Walid Kamal Abdelbasset, Editor PONE-D-22-01757R1Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in panic disorder – an exploratory studyPLOS ONE Dear Dr. Wintermann, 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 Aug 18 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, Walid Kamal Abdelbasset, Ph.D. 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 #1: All comments have been addressed Reviewer #2: (No Response) ******** 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: (No Response) Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) 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 #1: (No Response) Reviewer #2: No ****** 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: (No Response) 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 #1: (No Response) Reviewer #2: The revised version of paper titled (Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in panic disorder – an exploratory study) is improved compared to the original submission. I find it necessary that authors change (therapy outcome) int he title to (therapeutic outcome) ****** 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 ******** [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. https://doi.org/10.1371/journal.pone.0273413.r004
Revision 2
4 Jul 2022 Author Response 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. Response: We have now published the English study protocol on protocols.io with the following DOI http://dx.doi.org/10.17504/protocols.io.eq2lynbervx9/v1. A sentence regarding the publication of the study protocol is included in the revised manuscript, as suggested by PlosOne (see page 6, lines 121-122). Dear Dr. Walid Kamal Abdelbasset , Dear editors, thank you for your further interest in our manuscript entitled „Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder – an exploratory study“. We have now changed the title according to the reviewer´s suggestion and adapted the term „therapy outcome“ throughout the manuscript. All changes are marked yellow. Please find attached our rebuttal letter with point-by-point replies (also marked yellow). Do not hesitate to contact me in case of further inquiries. Sincerely Yours, Gloria Wintermann (on behalf of all co-authors) 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. Response: We have included a statement in the front page of our manuscript and also in the statistical analyses, concerning the availability of our data (see title page, see page 11, lines 258-260). The data file and study protocol are available from the Open Science Framework (https://archive.org/details/osf-registrations-s76rw-v1, source https://osf.io/s76rw/, registration DOI 10.17605/OSF.IO/S76RW and identifier DOI 10.17605/OSF.IO/NE4G6). Reviewer #2: The revised version of paper titled (Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapy outcome in panic disorder – an exploratory study) is improved compared to the original submission. I find it necessary that authors change (therapy outcome) int he title to (therapeutic outcome) Thank you for this hint. We have adhered to your suggestion and replaced the word „therapy“ by „therapeutic“, throughout the whole manuscript, where appropriate. Attachments Attachment Submitted filename: Rebuttal_Letter_July_2022.docx https://doi.org/10.1371/journal.pone.0273413.r005
11 Jul 2022 Decision Letter - Walid Kamal Abdelbasset, Editor PONE-D-22-01757R2Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder – an exploratory studyPLOS ONE Dear Dr. Wintermann, 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 Aug 25 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, Walid Kamal Abdelbasset, Ph.D. 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 #1: (No Response) Reviewer #2: 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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors should include in the limitations section a statement to the effect that with the multiple statistical tests being performed in this limited sample that no adjustment to the p-value has been made for multiple testing and thus the p-values should be interpreted with caution. This was ignored in my previous review comment. Reviewer #2: The revised form of the manuscript titled ( Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder – an exploratory study) was revised adequately according to the reviewers' recommendations. ****** 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: Sawsan Zaitone ******** [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. 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Revision 3
11 Jul 2022 Author Response Dear ladies and gentlemen, thank you for the opportunity to revise and profoundly improve our manuscript entitled „Cortisol response under low intensity exercise during cognitive-behavioural therapy is associated with therapeutic outcome in panic disorder – an exploratory study“ by Wintermann, G.-B., Noack, R., Schmiedgen, S. and Weidner, K. We have tried to adhere to the reviewers´ requests and included the open points in the revised version of our manuscript. Changes are coloured. Please feel free to contact us in case of any further inquiries. Sincerely Yours, Gloria Wintermann (on behalf of all co-authors) 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 We have addressed this point in the limitations of the study and made a suggestion for designing future studies in this research field (see lines 485-503). Reviewer #2: Yes Reviewer #1: The authors should include in the limitations section a statement to the effect that with the multiple statistical tests being performed in this limited sample that no adjustment to the p-value has been made for multiple testing and thus the p-values should be interpreted with caution. This was ignored in my previous review comment. We have already addressed this point partly in the revised version of our manuscript. Bonferroni-correction was applied when bivariate correlations between psychopathology and cortsiol response, before and after the therapeutic intervention, were analysed (see lines 256-257). We have now added a comment, that results should be interpreted with caution and as preliminary since only a small sample size was enrolled (see lines 490-491). We have also made a suggestion for designing future sample sizes (lines 493-494). Above, we added a sentence that p-value adjustment for multiple testing was not applied in all statistical analyses (lines 495-496). Attachments Attachment Submitted filename: Rebuttal_Letter_July_2022.docx https://doi.org/10.1371/journal.pone.0273413.r007
9 Aug 2022 Decision Letter - Walid Kamal Abdelbasset, Editor Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder – an exploratory study PONE-D-22-01757R3 Dear Dr. Wintermann, 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, Walid Kamal Abdelbasset, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): All comments have been addressed. No further comments are required. Reviewers' comments: https://doi.org/10.1371/journal.pone.0273413.r008
Formally Accepted
23 Aug 2022 Acceptance Letter - Walid Kamal Abdelbasset, Editor PONE-D-22-01757R3 Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder – an exploratory study Dear Dr. Wintermann: 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. Walid Kamal Abdelbasset Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0273413.r009

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