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      Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care

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      , MPH 1 , , , MD 2 , , BA 3 , , PhD 4 , , MD, MPH 5 , , MD, MPH 6
      JAMA Network Open
      American Medical Association

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          Abstract

          This cohort study investigates whether gender-affirming care is associated with decreased depression, anxiety, and suicidality among transgender and nonbinary youths.

          Key Points

          Question

          Is gender-affirming care for transgender and nonbinary (TNB) youths associated with changes in depression, anxiety, and suicidality?

          Findings

          In this prospective cohort of 104 TNB youths aged 13 to 20 years, receipt of gender-affirming care, including puberty blockers and gender-affirming hormones, was associated with 60% lower odds of moderate or severe depression and 73% lower odds of suicidality over a 12-month follow-up.

          Meaning

          This study found that access to gender-affirming care was associated with mitigation of mental health disparities among TNB youths over 1 year; given this population's high rates of adverse mental health outcomes, these data suggest that access to pharmacological interventions may be associated with improved mental health among TNB youths over a short period.

          Abstract

          Importance

          Transgender and nonbinary (TNB) youths are disproportionately burdened by poor mental health outcomes owing to decreased social support and increased stigma and discrimination. Although gender-affirming care is associated with decreased long-term adverse mental health outcomes among these youths, less is known about its association with mental health immediately after initiation of care.

          Objective

          To investigate changes in mental health over the first year of receiving gender-affirming care and whether initiation of puberty blockers (PBs) and gender-affirming hormones (GAHs) was associated with changes in depression, anxiety, and suicidality.

          Design, Setting, and Participants

          This prospective observational cohort study was conducted at an urban multidisciplinary gender clinic among TNB adolescents and young adults seeking gender-affirming care from August 2017 to June 2018. Data were analyzed from August 2020 through November 2021.

          Exposures

          Time since enrollment and receipt of PBs or GAHs.

          Main Outcomes and Measures

          Mental health outcomes of interest were assessed via the Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scales, which were dichotomized into measures of moderate or severe depression and anxiety (ie, scores ≥10), respectively. Any self-report of self-harm or suicidal thoughts over the previous 2 weeks was assessed using PHQ-9 question 9. Generalized estimating equations were used to assess change from baseline in each outcome at 3, 6, and 12 months of follow-up. Bivariate and multivariable logistic models were estimated to examine temporal trends and investigate associations between receipt of PBs or GAHs and each outcome.

          Results

          Among 104 youths aged 13 to 20 years (mean [SD] age, 15.8 [1.6] years) who participated in the study, there were 63 transmasculine individuals (60.6%), 27 transfeminine individuals (26.0%), 10 nonbinary or gender fluid individuals (9.6%), and 4 youths who responded “I don’t know” or did not respond to the gender identity question (3.8%). At baseline, 59 individuals (56.7%) had moderate to severe depression, 52 individuals (50.0%) had moderate to severe anxiety, and 45 individuals (43.3%) reported self-harm or suicidal thoughts. By the end of the study, 69 youths (66.3%) had received PBs, GAHs, or both interventions, while 35 youths had not received either intervention (33.7%). After adjustment for temporal trends and potential confounders, we observed 60% lower odds of depression (adjusted odds ratio [aOR], 0.40; 95% CI, 0.17-0.95) and 73% lower odds of suicidality (aOR, 0.27; 95% CI, 0.11-0.65) among youths who had initiated PBs or GAHs compared with youths who had not. There was no association between PBs or GAHs and anxiety (aOR, 1.01; 95% CI, 0.41, 2.51).

          Conclusions and Relevance

          This study found that gender-affirming medical interventions were associated with lower odds of depression and suicidality over 12 months. These data add to existing evidence suggesting that gender-affirming care may be associated with improved well-being among TNB youths over a short period, which is important given mental health disparities experienced by this population, particularly the high levels of self-harm and suicide.

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          Most cited references40

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          A brief measure for assessing generalized anxiety disorder: the GAD-7.

          Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity. A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use. A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale. The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.
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            Development of a new resilience scale: the Connor-Davidson Resilience Scale (CD-RISC).

            Resilience may be viewed as a measure of stress coping ability and, as such, could be an important target of treatment in anxiety, depression, and stress reactions. We describe a new rating scale to assess resilience. The Connor-Davidson Resilience scale (CD-RISC) comprises of 25 items, each rated on a 5-point scale (0-4), with higher scores reflecting greater resilience. The scale was administered to subjects in the following groups: community sample, primary care outpatients, general psychiatric outpatients, clinical trial of generalized anxiety disorder, and two clinical trials of PTSD. The reliability, validity, and factor analytic structure of the scale were evaluated, and reference scores for study samples were calculated. Sensitivity to treatment effects was examined in subjects from the PTSD clinical trials. The scale demonstrated good psychometric properties and factor analysis yielded five factors. A repeated measures ANOVA showed that an increase in CD-RISC score was associated with greater improvement during treatment. Improvement in CD-RISC score was noted in proportion to overall clinical global improvement, with greatest increase noted in subjects with the highest global improvement and deterioration in CD-RISC score in those with minimal or no global improvement. The CD-RISC has sound psychometric properties and distinguishes between those with greater and lesser resilience. The scale demonstrates that resilience is modifiable and can improve with treatment, with greater improvement corresponding to higher levels of global improvement. Copyright 2003 Wiley-Liss, Inc.
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              Sensitivity Analysis in Observational Research: Introducing the E-Value.

              Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                25 February 2022
                February 2022
                25 February 2022
                : 5
                : 2
                : e220978
                Affiliations
                [1 ]Department of Epidemiology, University of Washington, Seattle
                [2 ]Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle
                [3 ]School of Medicine, University of Washington, Seattle
                [4 ]Department of Psychiatry and Behavioral Medicine, Department of Adolescent and Young Adult Medicine, Seattle Children’s Hospital, Seattle, Washington
                [5 ]University of California, San Diego School of Medicine, Rady Children's Hospital
                [6 ]Division of Adolescent Medicine, Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington
                Author notes
                Article Information
                Accepted for Publication: January 10, 2022.
                Published: February 25, 2022. doi:10.1001/jamanetworkopen.2022.0978
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Tordoff DM et al. JAMA Network Open.
                Corresponding Author: Diana M. Tordoff, MPH, Department of Epidemiology, University of Washington, UW Box 351619, Seattle, WA 98195 ( dtordoff@ 123456uw.edu ).
                Author Contributions: Diana Tordoff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Diana Tordoff and Dr Wanta are joint first authors. Drs Inwards-Breland and Ahrens are joint senior authors.
                Concept and design: Collin, Stepney, Inwards-Breland, Ahrens.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Tordoff, Wanta, Collin, Stepney, Inwards-Breland.
                Critical revision of the manuscript for important intellectual content: Wanta, Collin, Stepney, Inwards-Breland, Ahrens.
                Statistical analysis: Tordoff.
                Obtained funding: Inwards-Breland, Ahrens.
                Administrative, technical, or material support: Ahrens.
                Supervision: Wanta, Inwards-Breland, Ahrens.
                Conflict of Interest Disclosures: Diana Tordoff reported receiving grants from the National Institutes of Health National Institute of Allergy and Infectious Diseases unrelated to the present work and outside the submitted work. No other disclosures were reported.
                Funding/Support: This study was supported Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Preservation Development Authority.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                zoi220056
                10.1001/jamanetworkopen.2022.0978
                8881768
                35212746
                2d3ed4e6-25d0-44c4-b936-e6b249c7db10
                Copyright 2022 Tordoff DM et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 15 July 2021
                : 10 January 2022
                Categories
                Research
                Original Investigation
                Online Only
                Pediatrics

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