Exploring Mediators of Mental Health Service Use Among Transgender Individuals in Ontario, Canada.

OBJECTIVES: To determine if and to what degree neighbourhood-level marginalization mediates mental health service use among transgender individuals. METHODS: This retrospective cohort study identified 2,085 transgender individuals through data obtained from 4 outpatient community and hospital clinics in 3 large cities in Ontario, which were linked with administrative health data between January 2015 and December 2019. An age-matched 1:5 comparison cohort was created from the general population of Ontario. Outcome measures were analysed from March 2020 to May 2022. The primary outcome was mental health service utilization, which included mental health-related visits to primary care providers, psychiatrists, mental health- and self-harm-related emergency department visits, and mental health hospitalizations. Mediation variables included ethnic concentration, residential instability, dependency, and material deprivation at the neighbourhood level and were derived from the Ontario Marginalization Index. RESULTS: This study identified 2,085 transgender individuals from participating outpatient community and hospital clinics, who were matched to the general population (n = 10,425). Overall, neighbourhood-level marginalization did not clinically mediate mental health service use. However, transgender individuals were more likely to be exposed to all forms of neighbourhood-level marginalization, as well as having higher rates of health service use across all outcome measures. CONCLUSIONS: In this study, mental health service use among transgender individuals was not clinically mediated by marginalization at the neighbourhood level. This study highlights the need to explore marginalization and mental health service use at the individual level to better understand the mental health disparities experienced by transgender individuals and to ensure that health-care services are inclusive and affirming.

Detransition Narratives Trouble the Simple Attribution of Madness in Transantagonistic Contexts: A Qualitative Analysis of 16 Canadians' Experiences.

Emerging evidence suggests that transgender individuals are more likely than cisgender peers to receive a diagnosis with a primary mental disorder. Attributions of madness, though, may serve the social function of dismissing and discrediting transgender individual's self-perceptions. The narratives of individuals who stop or reverse an initial gender transition who also identify as living with mental health conditions can sometimes amplify these socio-political discourses about transgender people. Through a critical mental health lens, this article presents a qualitative analysis of 16 individuals who stopped or reversed a gender transition and who also reported a primary mental health condition. Semi-structured, virtual interviews were conducted with people living in Canada. Applying constructivist grounded theory methodology, and following an iterative, inductive approach to analysis, we used the constant comparative method to analyse these 16 in-depth interviews. Results show rich complexity such that participants narrated madness in nuanced and complex ways while disrupting biased attitudes that madness discredited their thoughts and feelings, including prior gender dysphoria. Instead, participants incorporated madness into expanding self-awareness and narrated their thoughts and feelings as valid and worthy. Future research must consider provider's perspectives, though, in treating mad individuals who detransitioned, since alternate gender-affirming care models may better support the identification and wellness of care-seeking individuals who may be identified (in the past, present, or future) as mad.

LGBTQ2S+ childbearing individuals and perinatal mental health: A systematic review.

BACKGROUND: The perinatal period may uniquely impact the mental health and wellbeing of lesbian, gay, bisexual, transgender, queer, and Two-Spirit (LGBTQ2S+) childbearing individuals. OBJECTIVES: To characterise and synthesise the experiences of LGBTQ2S+ childbearing individuals regarding perinatal mental health, including symptomatology, access to care and care-seeking. SEARCH STRATEGY: We conducted and reported a systematic review following PRISMA guidelines of eight databases (EMBASE, MEDLINE-OVID, CINAHL, Scopus, Web of Science: Core Collection, Sociological Abstracts, Social Work Abstract, and PsycINFO) from inception to 1 March 2021. SELECTION CRITERIA: Original, peer-reviewed research related to LGBTQ2S+ mental health was eligible for inclusion if the study was specific to the perinatal period (defined as pregnancy planning, conception, pregnancy, childbirth, and first year postpartum; includes miscarriages, fertility treatments and surrogacy). DATA COLLECTION AND ANALYSIS: Findings were synthesised qualitatively via meta-aggregation using the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI), and the ConQual approach. MAIN RESULTS: Our systematic search included 26 eligible studies encompassing 1199 LGBTQ2S+ childbearing participants. Using the JBI SUMARI approach, we reported 65 results, which we synthesised as six key findings. The studies described unique considerations for LGBTQ2S+ individuals' perinatal mental health, including heteronormativity, cisnormativity, isolation, exclusion from traditional pregnancy care, stigma, and distressing situations from the gendered nature of pregnancy. Many participants described a lack of knowledge from healthcare providers related to care for LGBTQ2S+ individuals. In addition, LGBTQ2S+ individuals described barriers to accessing mental healthcare and gaps in health systems. Strategies to improve care include provider education, avoidance of gendered language, documentation of correct pronouns, trauma-informed practices, cultural humility training and tailored care for LGBTQ2S+ people. CONCLUSIONS: Pregnancy, postpartum, and the perinatal period uniquely impacts the mental health and wellbeing of LGBTQ2S+individuals, largely due to systems-level inequities and exclusion from perinatal care. Healthcare providers should implement the identified strategies to improve perinatal care and address inequities.

"Mental Readiness" and Gatekeeping in Trans Healthcare.

Gatekeeping refers to clinicians' strict application of eligibility criteria to determine a trans patient's "fitness" to engage in medical transition, resulting in significant barriers to gender-affirming care. Gatekeeping often uses "mental readiness" as a prerequisite to medical transition, which contributes to patient distress and systemic discrimination. Changing international trans health guidelines (the new World Professional Association for Transgender Health Standards of Care version 8) recommends clinicians shift from a gatekeeping model towards an informed consent model, which improves access to care. This commentary offers recommendations on how clinicians can reconsider existing "mental readiness" frameworks around medical transition to facilitate improved access to care.

Transgender health in medical education.

Transforming our world the 2030 agenda for sustainable development is working towards a world that reflects equity, with universal respect for human dignity, pledging to leave no one behind. However, transgender and gender-diverse individuals experience significant health inequities, including negative health outcomes and multiple barriers to accessing care. In this article, we first highlight the health inequities that transgender and gender-diverse people face globally. We describe important aspects of transgender and gender-diverse health care, including the design and provision of health services, epidemiological considerations, transition-related care, changes in transition-related goals, cultural considerations, and political and legal issues. We then review the existing global literature on incorporating transgender health into medical curricula. We make a case for prioritizing improved education in medical schools on the specific health needs of transgender and gender-diverse people as part of addressing global health inequities in care. Our recommendations for comprehensive education on transgender health include cultural humility and anti-oppression training; involvement of transgender and gender-diverse community members; integration of transgender and gender-diverse health into curricula; practice-focused and in situ training; staff development in medical schools; and improving access to careers in medicine for transgender and gender-diverse people.

Transformer notre monde: le Programme de développement durable à l'horizon 2030 aspire à un monde où règne l'équité, le respect universel de la dignité humaine, et s'engage à ce que personne ne soit oublié. Pourtant, les individus transgenres et de genre variant subissent de profondes inégalités sur le plan sanitaire, qui affectent leur état de santé et compliquent grandement l'accès aux soins. Dans cet article, nous commençons par souligner les inégalités sanitaires auxquelles sont confrontés les individus transgenres et de genre variant à travers le monde. Nous évoquons d'importants aspects à prendre en compte pour les soins de santé aux personnes transgenres et de genre variant, parmi lesquels la conception et la fourniture de services de santé, les considérations d'ordre épidémiologique, les soins liés à la transition, l'évolution des objectifs liés à la transition, les facteurs culturels, ainsi que les enjeux politiques et juridiques. Nous examinons ensuite la littérature internationale consacrée à l'intégration de la santé transgenre dans les programmes d'enseignement médical. Nous soutenons que, dans le cadre de la lutte contre les inégalités sanitaires au niveau mondial, il faut privilégier une amélioration de l'enseignement dans les écoles de médecine afin de sensibiliser aux besoins spécifiques des individus transgenres et de genre variant en matière de santé. Nous avons formulé plusieurs recommandations en vue d'instaurer un enseignement qui tient compte de la santé des personnes transgenres: apprentissage anti-oppressif intégrant la notion d'humilité culturelle; implication de membres de la communauté transgenre et de genre variant; ajout de la santé transgenre et de genre variant dans les programmes de cours; formation centrée sur la pratique, dispensée sur le terrain; développement du personnel des écoles de médecine; et enfin, amélioration de l'accès aux carrières médicales pour les individus transgenres et de genre variant.

Transforming our world: the 2030 agenda for sustainable development (Transformar de nuestro mundo: la Agenda 2030 para el desarrollo sostenible) trabaja por un mundo que refleje la igualdad, con respeto universal por la dignidad humana, comprometiéndose a no dejar a nadie atrás. Sin embargo, las personas transgénero y con género diverso experimentan importantes desigualdades en materia de salud, incluidos resultados sanitarios negativos y múltiples obstáculos para acceder a la atención sanitaria. En este artículo, destacamos, en primer lugar, las desigualdades sanitarias a las que se enfrentan las personas transgénero y de género diverso en todo el mundo. Describimos aspectos importantes de la atención sanitaria a las personas transgénero y con género diverso, como el diseño y la prestación de servicios sanitarios, las consideraciones epidemiológicas, la atención relacionada con la transición, los cambios en los objetivos relacionados con la transición, las consideraciones culturales y las cuestiones políticas y jurídicas. A continuación, revisamos la documentación global existente sobre la incorporación de la salud transgénero en los planes de estudio de medicina. Defendemos la necesidad de dar prioridad a la mejora de la formación en las facultades de medicina sobre las necesidades sanitarias específicas de las personas transgénero y con género diverso como parte del tratamiento de las desigualdades sanitarias globales en la atención sanitaria. Nuestras recomendaciones para una educación integral sobre la salud de las personas transgénero incluyen la formación en humildad cultural y lucha contra la opresión; la participación de los miembros de la comunidad transgénero y con género diverso; la integración de la salud de las personas transgénero y con género diverso en los planes de estudio; la formación centrada en la práctica e in situ; el desarrollo del personal en las facultades de medicina; y la mejora del acceso a las carreras de medicina para las personas transgénero y con género diverso.

"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.

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.

Characteristics of Transgender Individuals With Emergency Department Visits and Hospitalizations for Mental Health.

OBJECTIVE: Transgender individuals experience significant oppression resulting in mental health disparities. Factors associated with their need for acute mental health care are unknown. This study compared characteristics of transgender individuals who presented for acute mental health care with population-based comparison samples. METHODS: This cross-sectional study examined transgender individuals who had a mental health-related emergency department (ED) visit (N=728) or hospitalization (N=454). Transgender individuals were identified, and their data were linked with health administrative data. The transgender ED and hospitalization samples were each compared with two samples: all individuals in Ontario who had an ED visit or hospitalization (unmatched) and individuals matched on age, region of residence, and mental health care utilization history. Individuals' sociodemographic and clinical factors were compared. RESULTS: After matching, transgender individuals in the ED sample were more likely than those in the comparison group to be in the lowest neighborhood income quintile (37% versus 27%) and the highest residential instability quintile (47% versus 38%) and to be diagnosed as having a mood (26% versus 19%) or personality disorder (4% versus 1%). Transgender individuals in the hospitalization sample were more likely to be in the lowest neighborhood income quintile (36% versus 27%) and the highest residential instability quintile (45% versus 35%) and to be diagnosed as having a mood (40% versus 35%) or personality disorder (5% versus 2%). CONCLUSIONS: Transgender individuals who accessed acute mental health care had unique sociodemographic and clinical factors associated with their presentation that persisted after matching. More research into the factors associated with their acute care presentation is warranted, including how experiences of marginalization play a role.

"I thought that I had to be alive to repay my parents": Filial piety as a risk and protective factor for suicidal behavior in a qualitative study of Chinese women.

Filial piety involves the Confucian view that children always have a duty to be obedient and to provide care for their parents. Filial piety has been described as both a risk and a protective factor in depression and suicide. This qualitative study aimed to explore the role of filial piety in the suicidal behavior of Chinese women. Qualitative interviews were conducted with Chinese women with a history of suicidal behavior living in the Beijing area (n = 29). Filial piety data were extracted and analyzed in accordance with constructivist grounded theory. The women described five specific family and filial piety factors and how they influenced their ability to fulfill family role obligations, which was described as a nexus connecting these factors to depression, suicidal behavior, and recovery. The five factors were: 1) rigidity of parental filial expectations, 2) perception of family relationships as positive/supportive or negative/harsh, 3) whether filial piety is of high or low personal value in the woman's life, 4) any experiences of rebellion leading to punitive consequences, and 5) how much filial piety she receives from her children. These factors could inform suicide risk assessments in this population. They can be harnessed as part of recovery and protect against future suicidal behavior.

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.

Lessons from a Canada-China cross-national qualitative suicide research collaboration.

A cross-national qualitative suicide study was conducted by Tsinghua University and the University of Toronto with two samples of Chinese women in Beijing and Toronto. The aim of this article is to reflect on lessons learned from this collaborative study. A literature review guided the analysis. A focus group was conducted with members of both research teams. A semi-structured interview guide was developed to explore the researchers' experiences of participating in the cross-national study. Focus group transcript data and observations from authors informed the analysis, situated in the existing literature on cross-national qualitative health research and guided by Baistow's cross-national research frame. Our study highlights how cross-national research involves conceptual and practical challenges that require negotiation. Such research also holds many opportunities, including (1) using a different cultural lens to understand differences and clarify similarities cross-culturally; (2) co-constructing knowledge through collaboration; (3) deconstructing one's own assumptions; and (4) engaging in an inspiring and empowering experience in collaboration.

"I think I am worth it. I can give up committing suicide": Pathways to recovery for Chinese-Canadian women with a history of suicidal behaviour.

This qualitative study explored the experiences and patterns of recovery of Chinese-born women living in Canada with a history of suicidal behaviour. It explores a number of dimensions of recovery including clinical, existential, functional, physical, and social. The women described engaging in "survival" recovery in the short term and "thriving" recovery in the long term, with survival strategies extending into the thriving phase of recovery during their complex path to it. The survival recovery phase included accessing culturally sensitive mental health care and obtaining social and instrumental support to help ensure safety, manage stress, and treat psychiatric symptoms. The thriving phase of recovery was described as involving six components: developing an explanatory model with their health care provider; undertaking a process of narrative reflection and prioritizing self-care; engaging in interdisciplinary care team support; engaging the support of family and friends; exploring spiritual and existential supports; and creating goals for the future and a sense of mastery. Through these six avenues, the women began to experience a sense of self-efficacy and agency that improved their ability to cope with stress and pressure, leading to building a life with meaning. The interviews provided insights into how clinical care can be improved and how practitioners can implement a more recovery-oriented approach to practice.

"I just couldn't step out of the circle. I was trapped": Patterns of endurance and distress in Chinese-Canadian women with a history of suicidal behaviour.

RATIONALE: Recent studies have highlighted higher rates of suicidal ideation and behaviour and associated themes of gender role stress in Chinese women residing in North America. However, qualitative studies, which privilege their voices in the discourse of suicide prevention and provide insight into their experiences, are lacking. OBJECTIVE: To gain an understanding of the life histories, patterns of distress and constructions of suicide of Chinese-Canadian women with a history of suicidal behaviour. METHODS: Ten women were recruited from four mental health programs in Toronto, Canada and participated in qualitative interviewing and analysis informed by constructivist grounded theory. RESULTS: Chinese-Canadian women describe experiencing "stress" or "pressure" leading to the exacerbation of depressive symptoms. Stress and pressure are managed through a coping strategy of endurance, informed by the cultural conception of "ren". Cultural influences contribute to the manifestation of stress and pressure as somatic symptoms and sleeplessness. Finally, the women describe feeling unable to endure through worsening distress, reaching a "breaking point"; suicidal behaviour is constructed as a strategy to disrupt this cycle. CONCLUSION: This study challenges the binary notion that suicidal behaviour is either a consequence of mental illness or a reaction to interpersonal stress. Rather, the women describe an ingrained pattern of enduring through psychosocial problems without acknowledging worsening anxiety, depressive and physical symptoms. The pattern of endurance also prevents early treatment of these difficulties, resulting in the intensification of symptoms until a breaking point is reached. Knowledge of these patterns and coping strategies can allow for earlier identification and intervention for women at risk to prevent the worsening of distress leading to suicidal thoughts and behaviour.

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.