In August 2022, a cross-sectional survey was conducted with a nationwide US sample of young adults recruited and enrolled through Prolific, a survey platform that hosts a diverse panel of adults aged ≥18 years. The survey was conducted as part of TransHealthGUIDE, a National Institutes of Health (NIH)-funded project (U01MH136558) aimed at designing and implementing strategies to address mental health disparities among TGD young adults. Early in-depth key informant interviews with TGD young adults, caregivers, and health care providers identified the need to better understand the context of depression among TGD young adults. Specifically, the interviews highlighted the need for further information on the characteristics of TGD young adults with and without depression, the role of family, mental health service utilization, peer support, and recalled help-seeking behaviors in adolescence. This exploratory self-reported survey was developed as an extension of the key informant interviews and was designed to expand upon and quantify each of these factors for intervention development.

Eligibility criteria included: age 18‐25 years, TGD identity (self-identifying as TGD or having a gender identity different from sex assigned at birth), and US residency. The sample was stratified to enroll approximately 50 Black, Indigenous, and People of Color (BIPOC) people and 50 White young people. A total of 104 individuals were surveyed; additional details on survey methodology can be found elsewhere [21].

This exploratory survey was designed to be complementary to key informant interviews conducted with TGD young adults, caregivers, and health care providers as part of the NIH-funded TransHealthGUIDE project. After an initial round of key informant interviews, the research team identified the need for feedback from a larger group of diverse TGD young adults, than those were accessible for the interviews, and designed this survey to capture additional feedback.

Descriptive statistics (ie, frequencies, percentages, means, standard deviations) summarized variables for the overall sample and by PHQ-2 depression status. Bivariate tests (2-tailed t tests for continuous variables; χ² tests for binary or categorical variables) were used to compare participants with and without depression detected using PHQ-2. Poisson regression models with robust variance were fit to estimate prevalence ratios (PR) and 95% CI for correlates of depression [23]. Bivariate models were fit for each variable, followed by a single multivariable model with all variables to estimate adjusted prevalence ratios (aPR). Variables for modeling were selected a priori through a review of existing TGD research, conceptual salience, and findings from key informant interviews. Analyses were conducted using R software (version 4.4.3; R Foundation for Statistical Computing) [24] with statistical significance at P<.05 [24].

After review, the study protocol was deemed exempt by the Boston Children’s Hospital Institutional Review Board (IRB-P00043127). This study was performed in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent amendments. Participants completed an informed consent process. This was an anonymized survey, and participants indicated consent by opting into the survey. Participants were compensated $3 for completing the survey in accordance with the standards of the Prolific survey platform.

Sample characteristics are displayed in Table 1 for the total sample and stratified by PHQ-2 depression scores. Overall, 44 of 104 (42%) of the sample had clinically elevated depressive symptoms.

Participants’ mean age was 21.8 (SD 1.9) years; a total of 25/104 (24%) were BIPOC multiracial individuals, while 23/104 (22%) were BIPOC monoracial individuals, and 69/104 (66%) participants identified as nonbinary. The majority (n=64, 61%) of participants resided in a suburban area, and 11/104 (11%) did not have health insurance. Regarding their religious affiliation, 68 (65%) participants described themselves as unaffiliated, while 55 (53%) described their family’s religion as Christian. Half (49/104, 47%) of the participants were not out to their family, 31 (30%) reported low family support, while 24 (23%) participants reported high family support.

Among the participants, 56 (46%) had received mental health therapy and 28 of 104 (27%) had participated in a peer support group. When asked to recall their mental health needs during adolescence: 59 (57%) participants reported seeking information about mental health support or therapy, 88 (85%) indicated that reliable information on mental health support or therapy would have been useful, and 53 (51%) participants expressed having had an interest in therapy related to their gender.

In bivariate models (Table 2), increased PHQ-2 depression prevalence was associated with (1) being BIPOC multiracial versus White (PR1.39; 95% CI 1.05‐1.84), (2) having low family support versus high (PR 1.53; 95% CI 1.09‐2.15), (3) seeking information about mental health therapy in adolescence (PR 1.31; 95% CI 1.02‐1.67), and (4) being interested in mental health therapy related to gender during adolescence (PR 1.41; 95% CI 1.09‐2.05). Conversely, residing in a rural versus suburban area was associated with decreased PHQ-2 depression prevalence (PR 0.54; 95% CI 0.32‐0.92). No other variables reached statistical significance in bivariate models.

In a multivariable model (Table 2), after adjusting for all other variables, identifying one’s own religion as not Christian versus unaffiliated (aPR 1.66; 95% CI 1.04‐2.63) and low family support (aPR 1.54; 95% CI 1.05‐2.27) were associated with increased prevalence of positive depression screening. Residing in a rural versus suburban area (aPR 0.48; 95% CI 0.26‐0.92) and ever receiving mental health therapy (aPR 0.71; 95% CI 0.53‐0.97) were associated with decreased PHQ-2 depression prevalence in this model. Age, race or ethnicity, gender identity, US Census region, health insurance, family religion, peer support, history of interest in mental health therapy for gender during adolescence, frequency of information-seeking about mental health resources in adolescence, and desire for reliable mental health information during adolescence, were not significantly correlated with depression based on PHQ-2 scores.

In this nationwide online study, depression identified using PHQ-2 scores was highly prevalent, with more than 4 in 10 TDG young adults showing clinically elevated symptoms. Low levels of family support and nonChristian religious affiliation were associated with an increased likelihood of positive PHQ-2 depression screening. This exploratory study highlights the high rates of depressive symptoms among TGD young adults as well as the need for tailored interventions to improve mental health among those at the highest risk.

This study found that TGD young people with low family support had a higher prevalence of PHQ-2 depression compared to those with highly supportive families. This finding corroborates prior research on the protective role of family support on TGD young peoples’ mental health and has informed intervention development for the broader TransHealthGUIDE study [15,16]. For example, a key intervention component that has been developed for the overall study includes app-based education for TGD young adults and their caregivers on ways to improve family communication, connection, and support.

No differences in PHQ-2 depression prevalence were found for family religion, despite religious affiliation influencing attitudes toward TGD issues in the United States [18,19]. The TGD young people identifying their own religion as nonChristian (eg, Jewish, Muslim, Buddhist) had a higher prevalence of PHQ-2 depression than those identifying as unaffiliated; however, no significant differences were found between Christian and unaffiliated TGD young adults. The association between religious affiliation and depression has been inconsistent in prior research on young people [25], including a recent systematic review of religion, spirituality, and mental health among TGD youth [17]. Future mental health research may benefit from measuring not only religious affiliation but also the degree of religiosity, which was not assessed in this study.

This study found that a history of mental health help-seeking, specifically in young adults receiving mental health therapy was significantly associated with reduced PHQ-2 depression prevalence. This highlights the need for interventions that connect TGD young adults to necessary mental health services. The American Academy of Pediatrics recommends that adolescents aged 12 years and older be screened annually for depression using a formal self-report screening tool to identify and treat those with depression early in the course of illness, potentially reducing long-term depression-related morbidities [26]. This finding underscores the importance of improving mental health care access for TGD young adults to address depression, including telehealth and other online or digitally delivered services and interventions [27].

Regarding sociodemographic differences, we found no evidence of gender identity differences in PHQ-2 depression prevalence, inconsistent with prior research demonstrating the highest depression burden among nonbinary young adults [9]. However, previous studies have reported mixed findings regarding gender identity differences in depression [13], suggesting the need for ongoing research. While BIPOC multiracial TGD young people exhibited elevated PHQ-2 depression in bivariate analyses, consistent with national US population data, this finding did not remain significant in the adjusted model [3]. Geographic context emerged as a significant factor in this study, in alignment with psychiatric epidemiologic research showing lower depression rates in rural settings in high-income countries [28]. The TGD young adults residing in rural areas had lower PHQ-2 depression prevalence compared to those living in suburban areas. Prior studies have found greater mental distress symptoms among rural versus nonrural TGD adults but did not distinguish between the urban and suburban subgroups [29]. More recent research identified the lowest levels of depressive symptoms in rural versus urban-dwelling TGD adults [30]. Additional research is needed to better understand PHQ-2 depression prevalence and set of symptoms among TGD young adults in rural, urban, and suburban settings.

These findings should be interpreted alongside this study’s limitations. First, analyses were exploratory, and the small sample size limits statistical power to detect significant associations; the findings will require replication. Further, given the cross-sectional design, the study findings are associational only, and longitudinal research is recommended. Second, related to study measures, the global measure of family support may have overlooked important details about family dynamics, such as communication, acceptance, and explicit expressions of care and support [31]. Relatedly, mental health care utilization variables were self-reported rather than objectively measured. Future research that includes self-reported data alongside electronic health record data would strengthen the evidence base. Third, this study did not assess nonpsychiatric aspects of participants’ medical histories, and unmeasured confounding due to gender-affirming medical treatments cannot be ruled out [10,12]. Lastly, there are few validated measures for assessing mental health help-seeking behaviors [32]. Further research to understand online help-seeking behaviors for TGD young people using validated measures is warranted to inform future interventions [33].

The high prevalence of PHQ-2 depression in this online sample of TGD young adults underscores the importance of universal screening for depression in this population. It also highlights the need for appropriate systems to ensure prompt diagnosis, treatment, and follow-up for TGD young adults with PHQ-2 depression. Further, tailored interventions may be necessary for subgroups at increased risk for depression, such as TGD young adults with low family support, to decrease mental health disparities. The continued expansion of online interventions may facilitate the engagement of TGD young adults who would benefit from mental health prevention and treatment efforts [27]. This study’s findings have important implications for clinical care and the design, development, and implementation of interventions aimed at improving mental health outcomes and reducing health disparities among TGD young adults.