A cross-sectional survey-based exploration of diversity in the admissions committees and student cohorts of genetic counseling programs over time.

As of 2022, 89% of genetic counselors report being White, and 93% report being women. We examined diversity in genetic counseling (GC) program admission committees (ACs-who are responsible for deciding who will make up the future GC workforce) and student cohorts to understand the impact of recent diversification efforts, and where future work should be focused. One representative from each AC of the 57 accredited GC programs in North America in 2022 was invited to participate in a cross-sectional survey to provide information on the diversity of GC ACs and student cohorts between 2019 and 2022 for the following dimensions: race/ethnicity, gender, sexual orientation, disability status, neurodiversity, and rural or low socioeconomic status backgrounds. Members of 38/57 (67%) ACs participated. Using the Cochran-Armitage test for trends, significant increases were observed for the proportion of individuals of a racial/ethnic minority within ACs (from 9% in 2019 to 18% in 2022; p < 0.0001). There was no change for other minoritized social identities. There was no significant change over time in the proportion of students holding any of the minoritized social identities. A low correlation was found between the diversity of ACs and student cohorts. This study reaffirms the need for greater diversification efforts within ACs and student cohorts. Increased transparency about the social identities of AC members and about ACs' commitment to diversification may facilitate the diversification of the profession.

Psychological state at the time of psychiatric genetic counseling impacts patient empowerment: A pre-post analysis.

Psychiatric genetic counseling (GC) has been associated with patient-reported increases in empowerment (perceived control, emotional regulation, and hope). We sought to evaluate the extent to which patients' psychological state at the time of GC is related to changes in empowerment. Participants with a history of major depressive disorder and/or bipolar disorder that had been refractory to treatment underwent psychiatric GC remotely from 2022 to 2023. GC was performed by four genetic counselors and included discussion of perceived causes of illness, multifactorial inheritance, and protective factors. Empowerment, depression, and anxiety were measured immediately prior to GC via online survey by the GCOS-16, PHQ-9, and GAD-7, respectively. Empowerment was re-assessed 2 weeks later. In total, 66/161 (41.0%) invited individuals completed both the baseline and follow-up surveys. Participants completing both surveys were 54.6% female, 84.8% white, and ranged in age from 22 to 78 years (mean = 54.8 years). Overall, a significant change in mean empowerment was not observed (p = 0.38); however, there were moderating effects by baseline psychological state. A multiple linear regression model incorporating PHQ-9, GAD-7 and baseline GCOS-16 score predicted change in empowerment with a large effect (F = 5.49, R2 = 0.21, p < 0.01). A higher score on the PHQ-9 was associated with decreases in empowerment from pre to post GC. Higher scores on the GAD-7 and lower baseline GCOS-16 scores were associated with increases in empowerment. Further, two-way ANOVA was conducted to assess change in empowerment between subgroups based on the level of anxiety and depression. Those with low depression and high anxiety reported significant increases in empowerment (F = 6.64, p = 0.01). These findings suggest that psychiatric GC may be especially helpful to individuals experiencing anxiety and low baseline empowerment. Alternative approaches may be needed to best meet the needs of those experiencing significant depression.

The effectiveness of psychiatric genetic counseling training: An analysis of 13 international workshops.

Studies have consistently shown that psychiatric genetic counseling (pGC) helps people with psychiatric conditions by increasing empowerment and self-efficacy, and addressing emotions like guilt. Yet, it is not routinely provided. Genetic counselors and trainees express low confidence in their ability to provide meaningful pGC, especially in the absence of adequate training. Therefore, to address this gap a "Psychiatric Genetic Counseling for Genetic Counselors" (PG4GC) workshop was developed and delivered to 13 groups of participants (primarily qualified genetic counselors and trainees) between 2015 and 2023 (10 workshops were delivered in-person, and three virtually). Participants completed quantitative questionnaires both before and after completing the workshop to assess their comfort, knowledge, behavior, and feeling of being equipped to provide pGC. In total, 232 individuals completed the pre-workshop questionnaire and 154 completed the post-workshop questionnaire. Participants felt more comfortable, knowledgeable, and equipped to provide pGC, and reported being more likely to address psychiatric concerns after the workshop, regardless of whether they were trainees or practicing professionals and whether they completed the workshop in-person or virtually. This study suggests that the PG4GC workshop is an effective educational tool in pGC training that may aid in broader implementation of the service.

A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

BACKGROUND: Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. METHODS AND ANALYSIS: Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. CONCLUSION: SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patient partner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.

Assessing the impact of psychiatric genetic counseling on psychiatric hospitalizations.

Psychiatric genetic counseling (pGC) can improve patient empowerment and self-efficacy. We explored the relationship between pGC and psychiatric hospitalizations, for which no prior data exist. Using Population Data BC (a provincial dataset), we tested two hypotheses: (1) among patients (>18 years) with psychiatric conditions who received pGC between May 2010 and Dec 2016 (N = 387), compared with the year pre-pGC, in the year post-pGC there would be fewer (a) individuals hospitalized and (b) total hospital admissions; and (2) using a matched cohort design, compared with controls (N = 363, matched 1:4 for sex, diagnosis, time since diagnosis, region, and age, and assigned a pseudo pGC index date), the pGC cohort (N = 91) would have (a) more individuals whose number of hospitalizations decreased and (b) fewer hospitalizations post-pGC/pseudo-index. We also explored total days in hospital. Within the pGC cohort, there were fewer hospitalizations post-pGC than pre- pGC (p = 0.011, OR = 1.69), and total days in hospital decreased (1085 to 669). However, when compared to matched controls, the post-pGC/pseudo index change in hospitalizations among pGC cases was not statistically significant, even after controlling for the higher number of hospitalizations prior. pGC may lead to fewer psychiatric hospitalizations and cost savings; further studies exploring this are warranted.

Psychiatrists' perceptions of and reactions to a simulated psychiatric genetic counseling session.

Psychiatric genetic counseling (pGC) has been demonstrated to have meaningful positive outcomes for people with psychiatric conditions and their families. However, it is not widely accessed, and clinical genetics services tend to receive few referrals for these indications. Little research has evaluated psychiatrists' perceptions of and experience with interfacing with pGC. Therefore, we invited Ontario-based psychiatrists to participate in a study in which they first watched a simulated pGC session (representative of typical practice: the patient had depression with no exceptionally dense family history of psychiatric conditions, no genetic testing is provided, and no family-based risk assessment is performed), then completed zoom-based qualitative semi-structured interviews. Interviews were recorded, transcribed verbatim and checked for accuracy. Using interpretive description to analyze interviews with 12 psychiatrists (data collection was stopped at this point, as theoretical sufficiency was achieved), we generated two theoretical models: the first described the decision-making pathway psychiatrists currently follow when determining whether and how to address genetics with a patient; the second described psychiatrists' ideas for integrating pGC into care models for the future. Our data shed light on how to facilitate the delivery of pGC for people with psychiatric conditions and their families.

Costs of major depression covered / not covered in British Columbia, Canada.

BACKGROUND: Major depressive disorder (MDD) is one of the world's leading causes of disability. Our purpose was to characterize the total costs of MDD and evaluate the degree to which the British Columbia provincial health system meets its objective to protect people from the financial impact of illness. METHODS: We performed a population-based cohort study of adults newly diagnosed with MDD between 2015 and 2020 and followed their health system costs over two years. The expenditure proportion of MDD-related, patient paid costs relative to non-subsistence income was estimated, incidences of financial hardship were identified and the slope index of inequality (SII) between the highest and lowest income groups compared across regions. RESULTS: There were 250,855 individuals diagnosed with MDD in British Columbia over the observation period. Costs to the health system totalled >$1.5 billion (2020 CDN), averaging $138/week for the first 12 weeks following a new diagnosis and $65/week to week 52 and $55/week for weeks 53-104 unless MDD was refractory to treatment ($125/week between week 12-52 and $101/week over weeks 53-104). The proportion of MDD-attributable costs not covered by the health system was 2-15x greater than costs covered by the health system, exceeding $700/week for patients with severe MDD or MDD that was refractory to treatment. Population members in lower-income groups and urban homeowners had disadvantages in the distribution of financial protection received by the health system (SII reached - 8.47 and 15.25, respectively); however, financial hardship and inequities were mitigated province-wide if MDD went into remission (SII - 0.07 to 0.6). CONCLUSIONS: MDD-attributable costs to health systems and patients are highest in the first 12 weeks after a new diagnosis. During this time, lower income groups and homeowners in urban areas run the risk of financial hardship.

Cost-effectiveness of pharmacogenomic-guided treatment for major depression.

BACKGROUND: Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants. METHODS: We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC. RESULTS: Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation. INTERPRETATION: Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.

Development and evaluation of an educational resource for parents of children with 22q11.2 deletion syndrome about the psychiatric manifestations of the condition.

Parents of children with 22q11.2 deletion syndrome (22q11DS) report concern about the psychiatric manifestations of the condition, but typically receive little information about this in clinical encounters and instead find information about it elsewhere. We developed an educational booklet about the psychiatric manifestations of 22q11DS and assessed its utility among parents of children with the condition. First, six parents of individuals with 22q11DS completed cognitive interviews to review an established generic booklet about the genetics of psychiatric conditions-and to suggest 22q11DS-specific adaptations. We used these suggestions to develop a novel booklet specific to psychiatric conditions and 22q1DS. Then, before and 1-month after reading the novel 22q11DS-specific online booklet, 73 parents of children with 22q11DS (with/without psychiatric conditions) completed validated scales (measuring empowerment, stigma, intolerance of uncertainty), an adapted version of a scale measuring worry about their child developing psychiatric illness, and purpose-designed items assessing perceptions of understanding of 22q11DS and mental illness, confidence in recognizing early signs, etc. After reading the 22q11DS online booklet, participants' feelings of empowerment increased (p = 0.002), while feelings of worry about their child developing psychiatric illness decreased (p = 0.05), and they reported better understanding 22q11DS and mental illness, and increased confidence in recognizing early warning signs. There is potential benefit in broadly distributing this educational booklet to parents of children with 22q11DS.

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.