Discontinuation of Gender-Affirming Medical Treatments: Prevalence and Associated Features in a Nonprobabilistic Sample of Transgender and Gender-Diverse Adolescents and Young Adults in Canada and the United States.

PURPOSE: This study investigated the prevalence, correlates, and reasons for discontinuing gender-affirming medical treatment (GAMT) among transgender and gender-diverse adolescents and young adults living in Canada and the United States of America. METHODS: This exploratory study used data from an online survey of sexual and gender minority adolescents and young adults aged 15-29 years living in Canada or the United States of America (March-August 2022). The analytic sample was constituted by participants who responded to questions regarding starting and stopping GAMT, as well as reasons for stopping. Correlates of discontinuing GAMT were assessed using univariate logistic regression. RESULTS: The mean age of the analytic sample (N = 3,937) was 21.1 years. Participants were predominantly nonbinary (54.2%) and assigned female at birth (80.8%). 75.5% lived in Canada and 24.5% in the United States of America. Among those who had started GAMT, 121 of 720 (16.8%) reported having ever discontinued treatment. Forty five of 121 (37.2%) who ceased GAMT reported "Yes, but I wish I hadn't." The most frequently endorsed reasons for discontinuing GAMT were health reasons (37.3%), a change in gender identity (32.0%), and cost (16.0%). Greater age; nonbinary identity, 'other' gender identity; diagnosis of or self-identifying as living with schizophrenia; residing in the United States of America (relative to Canada); and endorsing a current Christian identity were associated with discontinuation. Ninety seven of 121 (80.2%) who discontinued GAMT reported a current transgender or gender-diverse identity. DISCUSSION: Given the dearth of information about the subpopulation who discontinue GAMT, this study advances candidate factors to inform future longitudinal research to better understand the multiple reasons and contexts for stopping GAMT.

Exploring the gender care experiences and perspectives of individuals who discontinued their transition or detransitioned in Canada.

BACKGROUND: Those who detransition have received increased public and scholarly attention and their narratives are often presented as evidence of limitations with contemporary gender-affirming care practices. However, there are scant empirical studies about how this population experienced their own process of gaining access to gender-affirming medical/surgical interventions, or their recommendations for care practice. AIMS: To qualitatively explore the care experiences and perspectives of individuals who discontinued or reversed their gender transitions (referred to as detransition). METHODS: Between October 2021-January 2022, Canadian residents aged 18 and older with experience of stopping, shifting, or reversing a gender transition were invited to participate in semi-structured, one-on-one, virtual interviews. A purposive sample of 28 was recruited by circulating study adverts over social media, to clinicians in six urban centres, and within participants' social networks. Interviews ranged between 50-90 minutes, were audio-recorded, and transcribed verbatim. Following constructivist grounded theory methodology, interview data were analyzed inductively and thematically following a two-phase coding process to interpret participants' experiences of, and recommendations for, gender care. RESULTS: Participants were between the ages of 20-53 (71% were between 20-29). All participants identified along the LGBTQ2S+ spectrum. Twenty-seven out of 28 of the participants received medical/surgical interventions (60% were ages 24 and younger). A majority (57%) reported three or more past gender identities, with 60% shifting from a binary transgender identity at the time of initiating transition to a nonbinary identity later in their transition journey. To access medical/surgical interventions, most participants were assessed via the gender-affirming care model pathway and also engaged in talk therapy with a mental healthcare provider such as a psychologist or psychiatrist. Some participants experienced their care as lacking the opportunity to clarify their individual treatment needs prior to undergoing medical/surgical transition. Decisional regret emerged as a theme alongside dissatisfaction with providers' "informed consent" procedures, such that participants felt they would have benefitted from a more robust discussion of risks/benefits of interventions prior to treatment decision-making. Overall, participants recommended an individualized approach to care that is inclusive of mental healthcare supports. CONCLUSIONS: To optimize the experiences of people seeking and receiving gender care, a thorough informed consent process inclusive of individualized care options is recommended, as outlined by the World Professional Association of Transgender Health, standards of care, version 8.

Predictors of suicide at time of diagnosis in schizophrenia spectrum disorder: A 20-year total population study in Ontario, Canada.

BACKGROUND: Suicide is a major cause of mortality for individuals with schizophrenia spectrum disorders (SSD). Understanding the risk factors for suicide at time of diagnosis can aid clinicians in identifying people at risk. METHODS: Records from linked administrative health databases in Ontario, Canada were used to identify individuals aged 16 through 45 years who received a first lifetime diagnosis of SSD (schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS)) using a validated algorithm between 01/01/1993 and 12/31/2010. The main outcome was death by suicide following cohort entry until 12/31/2012. OUTCOMES: 75,989 individuals with a first SSD diagnosis (60.1% male, 39.9% female) were followed for an average of 9.56 years. During this period, 1.71% of the total sample (72.1% male, 27.9% female) died by suicide, after an average of 4.32 years. Predictors of suicide death included male sex (HR 2.00, 95% CI 1.76-2.27), age at diagnosis between 26 and 35 (HR 1.27, 95% CI 1.10-1.45) or 36-45 (HR 1.34, 95% CI 1.16-1.54), relative to 16-25, and suicide attempt (HR 2.23, 95% CI 1.86-2.66), drug use disorder (HR 1.21, 95% CI 1.04-1.41), mood disorder diagnosis (HR 1.32, 95% CI 1.17-1.50), or mental health hospitalization (HR 1.30 95% CI 1.13-1.49) in the 2 years prior to SSD diagnosis. INTERPRETATION: Death by suicide occurs in 1 out of every 58 individuals and occurred early following first diagnosis of SSD. Psychiatric hospitalizations, mood disorder diagnoses, suicide attempts prior to SSD diagnosis, as well as a later age at first diagnosis, are all predictors of suicide and should be integrated into clinical assessment of suicide risk in this population.

"We Went Out to Explore, But Gained Nothing But Illness": Immigration Expectations, Reality, Risk and Resilience in Chinese-Canadian Women with a History of Suicide-Related Behaviour.

Suicide is a complex and tragic outcome driven by biological, psychological, social and cultural factors. Women of Chinese descent and women who have immigrated to other countries have higher rates of suicidal ideation and behaviour, and immigration-related stress may contribute. To understand the experiences of immigration and their relationship with distress and suicide-related behaviour in Chinese women who have immigrated to Canada. 10 semi-structured qualitative interviews with Chinese women who have immigrated to Toronto, Canada and have a history of suicide-related behaviour were completed and analyzed using a constructivist grounded theory methodology. Immigration-related and acculturation stress stemmed from unmet expectations and harsh realities. These repeated experiences resulted in hopelessness, helplessness, and alienation, which are risk factors for suicide and suicide-related behaviour. However, immigration-related support can also increase hope, self-efficacy and connectedness to foster recovery and resilience. This is the first qualitative study focusing on immigration experiences and its relationship to suicide-related behaviour in Chinese immigrant women. Knowledge of immigration and acculturation stressors can a) help identify and support women at risk for suicide and b) form a target for social intervention for all immigrant women, regardless of suicide risk.

Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus.

In the search for strategies to treat schizophrenia, attention has focused on enhancing NMDA receptor function. In vitro experiments show that metabotropic glutamate 5 receptor (mGluR5) activation enhances NMDA receptor activity, and in vivo experiments indicate that mGluR5 positive allosteric modulators (PAMs) are effective in preclinical assays measuring antipsychotic potential and cognition. Here we characterized the dose-effect function of CDPPB (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide), an mGluR5 PAM, on novel object recognition memory in unimpaired Wistar Hannover rats (0, 10 or 30 mg/kg CDPPB) and animals with an MK-801-induced deficit (0, 3, 10, or 30 mg/kg CDPPB). In each experiment compound was given 30 min prior to the first exposure in order to affect acquisition/consolidation of the memory. In both cases, an inverted-U-shaped dose-effect function was observed, with lower doses improving recognition but higher doses having no effect. We then examined the effects of CDPPB (0, 3, 10, or 30 mg/kg) on markers of synaptic plasticity in prefrontal cortex and hippocampus, focusing on the expression and phosphorylation status of proteins involved in NMDA related signaling, including the NMDA receptor subunits NR1 and NR2B, the AMPA receptor subunit GluR1, alphaCa((2+))/CaM dependent Ser-Thr kinases II (alphaCaMKII), and the transcription factor CREB. Expression and phosphorylation of many of these proteins, particularly in the prefrontal cortex, were also characterized by an inverted-U-shaped dose-effect function. Taken together, these findings show that mGluR5 activation enhances NMDA receptor function and markers of neuronal plasticity commensurate with improvements in recognition memory. However, the effects of CDPPB are heavily dependent on dose, with higher doses being ineffective in improving recognition memory and producing downstream effects consistent with heightened NMDA receptor activation. These findings may have important implications for the development of mGluR5 PAMs to treat schizophrenia.