Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health

Erica T. Warner; Ying Zhang; Yue Gu; Tâmara P. Taporoski; Alexandre Pereira; Immaculata DeVivo; Nicholas D. Spence; Yvette Cozier; Julie R. Palmer; Alka M. Kanaya; Namratha R. Kandula; Shelley A. Cole; Shelley Tworoger; Alexandra Shields

doi:10.1371/journal.pone.0241363

Peer Review History

Original SubmissionMay 5, 2020
22 Jun 2020 Decision Letter - Gabriele Saretzki, Editor PONE-D-20-13222 Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health PLOS ONE Dear Dr. Warner, 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 06 2020 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. 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In the Methods section, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: 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: This is an important study and of much merit. I do have some concerns about the data analyses that should be addressed. 1. Referencing is not always sufficiently contemporaneous for telomere biology/ageing. Citing reviews from 2007 for this topic is outdated. Please use more recent referencing. 2. Assays of <20% for biomarker CVs are simply not acceptable in the field for data to be considered to be robust. Typical inter and intra assay CVs are below 5% and in my experience typically below 3%. This needs addressed and discussed. 3. Discussion of whether sample collection was equivalent ( e.g. PBLs versus PBMC etc) shoudl be included. 4. Discussion of relative socio-economic position , living density , geo-physical environment and crucially diet and inflammatory statusat blood draw are crucial to providing proper context to assess just how robust data interpretations are. 5. Discussion of epigentic influences shoudl also be included. The authors are encouraged to see Laing et al Eur Child Adolesc Psychiatry. 2019 Apr 9. doi: 10.1007/s00787-019-01329-1. ****** 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. 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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.0241363.r001
Revision 1
9 Oct 2020 Author Response PONE-D-20-13222: Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health We appreciate the insightful feedback on the manuscript and for the opportunity to revise our manuscript to address it. Editorial 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. a. We updated author affiliations and removed key messages to meet format guidelines. 2. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. a. On page 4 we now state: “Each cohort study obtained written informed consent from their participants as well as institutional review board approval for cohort maintenance and participation in the SSSH.” Reviewer 1 1. Referencing is not always sufficiently contemporaneous for telomere biology/ageing. Citing reviews from 2007 for this topic is outdated. Please use more recent referencing. a. Thank you for your feedback. We previously chose to cite seminal papers that established key concepts related to telomere biology and aging. We have updated the literature review to include more recent references. 2. Assays of <20% for biomarker CVs are simply not acceptable in the field for data to be considered to be robust. Typical inter and intra assay CVs are below 5% and in my experience typically below 3%. This needs addressed and discussed. a. The CV’s presented in the manuscript we were for the exponentiated T:S ratio. These CV’s tend to be higher than raw CVs because they represent the ratio of a ratio. To address this concern, the laboratory calculated the inter and intra assay CVs and we now present those along with the CV for the exponentiated T:S ratio in the text. The inter and intra assay CV’s are all below 1.0%. The revised text, presented on page 7, is shown below. i. The total intra assay coefficients of variation (CV) ranged from 0.27% (NHSII) to 0.3% (MASALA) and the inter assay CVs ranged from 0.33% (MASALA) to 0.77% (SHS). CVs for the exponentiated T:S ratio ranged from 4.7% (SHS) to 10.3% (NHS). 3. Discussion of whether sample collection was equivalent (e.g. PBLs versus Peripheral blood mononuclear cells etc) should be included. a. We describe the processing and DNA extraction procedures in the Relative Telomere Length section of the methods on page 8 and 9: “Genomic DNA was extracted from peripheral blood leukocytes using the QIAmp (Qiagen) 96-spin blood protocol (BWHS and NHSII), phenol-chloroform standard protocol (SHS and BHS), or sodium dodecylsulfate cell lysis followed by a salt precipitation (MASALA).” b. According to Tolios et al. (doi.org/10.1371/journal.pone.0143889) DNA extraction methods, but not preanalytic storage conditions and other sample processing methods affect measured telomere length. We acknowledge this in the limitation section on page 13. We state: “DNA extraction methods differed between studies, which can influence RTL measurement. However, extraction methods were the same for all participants within a cohort, and we pooled cohort-specific estimates using meta-analysis, limiting the potential impact of this factor on our results.” 4. Discussion of relative socio-economic position, living density, geo-physical environment and crucially diet and inflammatory status at blood draw are crucial to providing proper context to assess just how robust data interpretations are. a. Data on characteristics of the participants’ geo-physical environment or inflammatory status was not available in the Study on Psychosocial Stress, Spirituality, and Health. However, adult characteristics associated with socioeconomic position and inflammation including, body mass index (BMI), household income, smoking status, physical activity, alternative healthy eating index (AHEI), and depressive symptoms are included in Table 1a and 1b, and we adjusted for them in our model 3. From a causal inference perspective, these factors cannot confound the association between abuse in childhood and adolescence and telomere length in adulthood because they occur after the exposure. We position them as potential mediators of the association, which could potentially operate differently across cohorts. However, adjustment for these current characteristics had relatively little impact on the association between abuse in childhood and adolescence and telomere length. Additionally, while there is significant variation between cohorts in these adult characteristics, we observed little evidence of heterogeneity in observed associations across cohorts suggesting that these factors were not effect modifiers. b. To provide more context for the studies, we moved text that describes the population of each study from supplemental table 1 to the methods section of the manuscript on pages 5-7. We have added text to the discussion on page 22 discuss the different populations data and the impact these differences might be expected to have on our results. We conclude that the consistency of association is evidence of the robustness of our findings. We state: “However, despite cohort differences in participant demographic characteristics, exposure assessment and sample processing, we observed consistent associations between severe sexual abuse and shortened telomeres.” 5. Discussion of epigenetic influences should also be included. The authors are encouraged to see Laing et al Eur Child Adolesc Psychiatry. 2019 Apr 9. doi: 10.1007/s00787-019-01329-1. a. We have added to the study limitations on p.22 the following text: “Additionally, our study evaluated associations with telomere length as a marker of accelerated aging, but other markers including DNA methylation, are important and their examination will enhance our understanding of the biological impact of abuse experienced in early-life.68 Our group has previously shown that childhood abuse victimization was associated with hypermethlation in NR3C1.39 Ongoing analyses within the Study on Psychosocial Stress, Spirituality, and Health are examining the impact of abuse and other stressful life experiences on DNA methylation within candidate genes in the stress pathway (HSD11B1, HSD11B2, NR3C1, FKBP5) and in epigenome-wide association studies.” Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0241363.r002
14 Oct 2020 Decision Letter - Gabriele Saretzki, Editor Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health PONE-D-20-13222R1 Dear Dr. Warner, 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, Gabriele Saretzki, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): The authors addressed any outstanding issue and clarified Cvs etc for the methodology, included a discussion of limitations etc. Reviewers' comments: https://doi.org/10.1371/journal.pone.0241363.r003
Formally Accepted
20 Oct 2020 Acceptance Letter - Gabriele Saretzki, Editor PONE-D-20-13222R1 Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health Dear Dr. Warner: 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. Gabriele Saretzki Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0241363.r004

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