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.

The journey from concealment to disclosure of an obsessive-compulsive disorder diagnosis in the high school setting: A qualitative study exploring youth perspectives.

Disclosure of an OCD diagnosis in the high school setting could allow for timely provision of individualized school-based supports. As few studies have examined adolescent perspectives on the disclosure process in schools, we adopted a qualitative approach to explore this, and to gather recommendations for making disclosure of OCD at school safer and more helpful. Twelve participants, ranging from 13 to 17 years old, were recruited using maximum variance-based heterogeneous purposive sampling. Semi-structured interviews were conducted and analyzed inductively through Interpretive Description. From participants' stories, we generated a theoretical model describing the journey from concealment of an OCD diagnosis to disclosure. Four phases of youth disclosure were identified: managing enacted and perceived stigma related to the diagnosis, internal bargaining to determine their individualized disclosure boundaries, trust building with school members, and empowerment by being treated as a person first. Participants' recommendations for the school setting included meaningful education, safe spaces, deep reciprocal connections, and confidential personalized support. The model we developed can help inform school disclosure strategies and optimize support to promote best outcomes for youth with OCD.

Considerations for the use of qualitative methodologies in genetic counseling research.

An abundance of qualitative research is being conducted within the genetic counseling field. As this area of research expands, many within our community are "learning through doing", an approach which is practical, but may lack theoretical grounding. This can result in study outputs that do not have the sort of utility for informing clinical practice that is the hallmark of excellent clinical qualitative research. Furthermore, our alignment as a discipline within the health sciences, which still tends to favor quantitative approaches, means that we may often be obliged to justify the use of qualitative methodologies, especially when we intend to use the findings for informing clinical practice. We aim to address these issues by providing guidance about how we, individually and collectively, might think about what excellent qualitative research can look like in our field. In addition to providing information and resources about current best-practices, we discuss how quality can be ensured and evaluated. We seek to legitimize the idea of developing a philosophy of research in pursuit of establishing genetic counseling as an academic discipline. We argue that the principles, ethics, values, and practices of genetic counseling are sufficiently unique that establishing a discipline-specific qualitative research framework is not only warranted, but essential. Ultimately, we hope that this paper can serve as a launching point from which additional discussion about qualitative research can emanate as we strive towards the elevation of this form of inquiry in our field.

Healthcare decision makers' perspectives on the creation of new genetic counselor positions in North America: Exploring the case for psychiatric genetic counseling.

Mental illnesses are common and highly heritable. Patients and their families want and benefit from receiving psychiatric genetic counseling (pGC). Though the pGC workforce is among the smallest of genetic counseling (GC) specialties, genetic counselors (GCs) want to practice in this area. A major barrier to the expansion of the pGC workforce is limited availability of advertised positions, but it remains unclear why this is the case. We used a qualitative approach to explore drivers for and barriers to the creation of GC positions (including pGC) at large centralized genetic centers in the United States and Canada that offer multiple specialty GC services. Individuals with responsibilities for making decisions about creating new clinical GC positions were interviewed using a semi-structured guide, and an interpretive description approach was used for inductive data analysis. From interviews with 12 participants, we developed a theoretical model describing how the process of creating new GC positions required institutional prioritization of funding, which was primarily allocated according to physician referral patterns, which in turn were largely driven by availability of genetic testing and clinical practice guidelines. Generating revenue for the institution, improving physician efficiency, and reinforcing institutional mission were all regarded as valued outcomes that bolstered prioritization of funding for new GC positions. Evidence of patient benefit arising from new GC positions (e.g., pGC) seemed to play a lesser role. These findings highlight the tension between how institutions value GC (generating revenue, reacting to genetic testing), and how the GC profession sees its value (providing patient benefit, focus on counseling).

A tool for translating polygenic scores onto the absolute scale using summary statistics.

There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. We also evaluate methods for estimating polygenic score AUC/R2 from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute ( https://opain.github.io/GenoPred/PRS_to_Abs_tool.html ). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.

Experiences With Genetic Counseling, Testing, and Diagnosis Among Adolescents With a Genetic Condition: A Scoping Review.

Importance: The number of adolescents who are diagnosed with a genetic disorder is increasing as genome sequencing becomes the standard of clinical diagnostic testing. However, the experience of receiving a diagnosis of a genetic condition has not been extensively studied in adolescents. Objective: To identify how adolescents with a genetic condition engage with genetic or genomic counseling services as well as interpret, adapt to, and experience their diagnosis. Evidence Review: A literature search of MEDLINE, Embase, CINAHL, and PsycINFO was undertaken. Articles (primary literature, knowledge syntheses, and gray literature) in English that investigated the experiences of adolescents between 10 and 19 years of age who received genetic or genomic counseling were included. Data were extracted from 45 eligible articles and analyzed descriptively. Findings: A total of 45 studies were included, most of which were quantitative in nature (21 of 45 [47%]) and conducted in the US (n = 13), followed by the UK (n = 8), Australia (n = 8), and Canada (n = 6). A total of 29 distinct monogenic disorders were investigated. Sample sizes ranged from 1 to 930, with a median of 23 participants, and the year of publication ranged from 1977 to 2019. Included studies addressed all aspects of genetic counseling, but a preponderance of articles assessed knowledge about genetic conditions (n = 17) and challenges of communication within families (n = 16). Fewer articles addressed the experiences of adolescents adapting to their genetic conditions (n = 8) and the genetic counseling process (n = 4). Only 1 study addressed any aspect of genetic counseling in relation to genome sequencing. Conclusions and Relevance: This scoping review found that most of the included studies focused on adolescents' knowledge about their genetic condition and communication about genetic risks, whereas fewer studies explored their adaptation to the condition and the genetic counseling process. A systematic reconsideration of the genetic counseling process may be undertaken to provide an evidence-informed health care service that is tailored to the needs of this adolescent population.

Out-of-pocket and private pay in clinical genetic testing: A scoping review.

Full coverage of the cost of clinical genetic testing is not always available through public or private insurance programs, or a public healthcare system. Consequently, some patients may be faced with the decision of whether to finance testing out-of-pocket (OOP), meet OOP expenses required by their insurer, or not proceed with testing. A scoping review was conducted to identify literature associated with patient OOP and private pay in clinical genetic testing. Seven databases (EMBASE, MEDLINE, CINAHL, PsychINFO, PAIS, the Cochrane Database of Systematic Reviews, and the JBI Evidence-Based Practice database) were searched, resulting in 83 unique publications included in the review. The presented evidence includes a descriptive analysis, followed by a narrative account of the extracted data. Results were divided into four groups according to clinical indication: (1) hereditary breast and ovarian cancer, (2) other hereditary cancers, (3) prenatal testing, (4) other clinical indications. The majority of studies focused on hereditary cancer and prenatal genetic testing. Overall trends indicated that OOP costs have fallen and payer coverage has improved, but OOP expenses continue to present a barrier to patients who do not qualify for full coverage.

Genetic counselling for the prevention of mental health consequences of cannabis use: A randomized controlled trial-within-cohort.

BACKGROUND: Cannabis use is a risk factor for severe mental illness. However, cannabis does not affect everyone equally. Genetic information may help identify individuals who are more vulnerable to the harmful effects of cannabis on mental health. A common genetic variant within the AKT1 gene selectively increases risk of psychosis, only among those who use cannabis. Therapeutically oriented genetic counselling may enable us to reduce cannabis exposure among genetically sensitive individuals. METHODS: Using a trial-within-cohort design, we aim to test if genetic counselling, including the option to receive AKT1 rs2494732 genotype, reduces cannabis use. To this end, we have designed a genetic counselling intervention: Interdisciplinary approach to Maximize Adolescent potential: Genetic counselling Intervention to reduce Negative Environmental effects (IMAGINE). RESULTS: IMAGINE will be implemented in a cohort of children and youth enriched for familial risk for major mood and psychotic disorders. Approximately 110 eligible individuals aged 12-21 years will be randomized in a 1:1 ratio to be offered a single genetic counselling session with a board-certified genetic counsellor, or not. Allocated youth will also be invited to attend a follow-up session approximately 1 month following the intervention. The primary outcome will be cannabis use (measured by self-report or urine screen) at subsequent annual assessments as part of the larger cohort study. Secondary outcomes include intervention acceptability and psychopathology. CONCLUSION: This study represents the first translational application of a gene-environment interaction to improve mental health and test an intervention with potential public health benefits. This study is registered with clinicaltrials.gov (NCT03601026).

Advancing the genetic counseling profession through research: Identification of priorities by the National Society of Genetic Counselors research task force.

To help advance research critical to the achievement of the National Society of Genetic Counselors' (NSGC) strategic objectives, coordination and prioritization of society resources are needed. NSGC convened a task force to advance research necessary for the achievement of our strategic objectives by reviewing existing society-supported research efforts identifying gaps in current research, and coordinating society resources, the task force was formed in order to coordinate and prioritize society resources to advance research critical to the achievement of our strategic objectives. The task force developed a research agenda outlining high-priority research questions for the next 5 years. The questions are organized into four domains: (a) Genetic Counseling Clients; (b) Genetic Counseling Process and Outcomes; (c) Value of Genetic Counseling Services; and (d) Access to Genetic Counseling Services. This framework can be used to advocate for research and funding priorities within NSGC and with other key research entities to stimulate the growth and advancement of the genetic counseling profession.

Evidence-Based Genetic Counseling for Psychiatric Disorders: A Road Map.

Psychiatric disorders, such as schizophrenia, depression, anxiety, and bipolar disorder, are common conditions that arise as a result of complex and heterogeneous combinations of genetic and environmental factors. In contrast to childhood neurodevelopmental conditions such as autism and intellectual disability, there are no clinical practice guidelines for applying genetic testing in the context of these conditions. But genetic counseling and genetic testing are not synonymous, and people who live with psychiatric disorders and their family members are often interested in what psychiatric genetic counseling can offer. Further, research shows that it can improve outcomes like empowerment for this population. Despite this, psychiatric genetic counseling is not yet routinely or widely offered. This review describes the state of the evidence about the process and outcomes of psychiatric genetic counseling, focusing on its clinical implications and remaining research gaps.

Psychiatric genetic counseling: A mapping exercise.

Psychiatric genetic counseling (PGC) is gradually developing globally, with countries in various stages of development. In some, PGC is established as a service or as part of research projects while in others, it is just emerging as a concept. In this article, we describe the current global landscape of this genetic counseling specialty and this field's professional development. Drawing on information provided by expert representatives from 16 countries, we highlight the following: (a) current understanding of PGC; (b) availability of services for patients; (c) availability of training; (d) healthcare system disparities and cultural differences impacting practice; and (e) anticipated challenges going forward.

Genetic counseling students' experiences with mental illness during training: An exploratory study.

Mental illness is a substantive issue for graduate students. We investigated experiences of mental illness during training among genetic counseling students, a subgroup of graduate students for which little data exists on this topic. Genetic counseling students and recent graduates (n = 227) completed an online survey, from who 11 were selected to participate in semi-structured telephone interviews. Thematic analysis and member checking were employed to interpret the interviews. An overarching theme of importance to participants' mental health during genetic counseling training was safety, with subthemes of: trust/confidentiality, stigma and fear of labeling, developing a unique professional identity, and ability to engage in self care strategies. Our data could help genetic counseling training programs develop strategies to support students' mental health.

Women's experiences of participating in a prospective, longitudinal postpartum depression study: insights for perinatal mental health researchers.

Barriers to recruitment for research on mental illness include participant distrust of researchers and social stigma. Though these issues may be acutely important in perinatal mental health research, they remain unexplored in this context. In order to inform strategies to more fully engage women in perinatal mental health research, we explored the motivations and experiences of women with a history of major depressive disorder who participated in a prospective longitudinal research study on postpartum depression (PPD). Sixteen women with a history of depression who had either completed or recently made a decision about participation in a longitudinal research study about PPD were interviewed by telephone. Qualitative, semi-structured interviews explored participants' decision-making about, and experiences of, participation. Interviews were audio-recorded, transcribed, and qualitatively analyzed using elements of grounded theory methodology. Follow-up interviews were conducted with four participants to refine and clarify preliminary results. Foundational elements necessary for women to consider participating in PPD research included personal acceptance of illness and trust in the research team/institution. Other main motivators included perceived personal relevance, anticipated benefits (including access to support/resources, learning opportunities, and improved self-worth), altruism, and accessible study procedures. Our data suggest that participating in perinatal mental health research may help women make meaning of their mental illness experience and is perceived as providing support. The findings-particularly around the importance of participant-researcher rapport and accessibility of study design-may inform strategies that improve participation rates, decrease attrition, and maximize participant benefits in perinatal mental health research.

2013 Review and Update of the Genetic Counseling Practice Based Competencies by a Task Force of the Accreditation Council for Genetic Counseling.

The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non-clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors' roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre-defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force's work, key changes and the 2013 PBCs are presented herein.

A pilot randomized clinical trial evaluating the impact of genetic counseling for serious mental illnesses.

OBJECTIVE: The serious mental illnesses schizophrenia, schizoaffective disorder, and bipolar disorder are complex conditions affecting 1% to 4% of the population. Individuals with serious mental illnesses express interest in genetic counseling, an intervention showing promise for increasing patient knowledge and adaptation. This trial aimed to evaluate the effects of genetic counseling for people with serious mental illnesses as compared to an educational intervention or wait list. METHOD: A pilot 3-arm (each n = 40; genetic counseling, a control intervention involving an educational booklet, or wait list), parallel-group, randomized clinical trial was conducted from September 2008 through November 2011 in Vancouver, Canada. Participants with schizophrenia, bipolar disorder, or schizoaffective disorder (DSM-IV) completed outcome measures assessing knowledge, risk perception, internalized stigma, and perceived control over illness at baseline and 1-month follow-up. The Brief Symptom Inventory was administered to control for current symptoms. Analyses included linear mixed-effects models and χ(2) tests. RESULTS: Knowledge increased for genetic counseling/educational booklet compared to wait list at follow-up (LRT1 = 19.33, Holm-adjusted P = .0003, R(2)LMM(m) = 0.17). Risk perception accuracy increased at follow-up for genetic counseling compared to wait list (Yates continuity corrected χ(2)1 = 9.1, Bonferroni P = .003) and educational booklet (Yates continuity corrected χ(2)1 = 8.2, Bonferroni P = .004). There were no significant differences between groups for stigma or perceived control scores. CONCLUSIONS: Genetic counseling and the educational booklet improved knowledge, and genetic counseling, but not the educational booklet, improved risk perception accuracy for this population. The impact of genetic counseling on internalized stigma and perceived control is worth further investigation. Genetic counseling should be considered for patients with serious mental illnesses. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00713804.

Perinatal psychosis in mothers with a history of major depressive disorder.

While women with a history of major depressive disorder (MDD) have higher chances for postpartum depressive and manic episodes, little is known about their chance for postpartum psychosis (PPP). We prospectively assessed the frequency of perinatal psychotic symptoms among primiparous women with a history of MDD only (structured clinical interview was used to exclude women with pre-existing histories of mania or psychosis) and explored whether sex of the baby influenced these symptoms.The presence of symptoms of psychosis was defined using previously established cutoff scores on five key items from the Positive and Negative Syndrome Scale (PANSS), which was administered during pregnancy, at 1 week, 1 month, and 3 months postpartum.Fourteen of 60 women (23%) scored above threshold for psychosis at one or more time points, with 6 experiencing postpartum onset. There was a non-significant trend (p = 0.073) towards higher frequency of these symptoms among mothers of girls.If controlled studies using diagnostic interviews confirm that psychotic symptoms are relatively common among women with MDD, monitoring for psychosis during the perinatal period may be indicated in this population. The potential effect of sex of the baby on mothers' chance for PPP requires further study.

Ethical issues associated with genetic counseling in the context of adolescent psychiatry.

Genetic counseling is a well-established healthcare discipline that provides individuals and families with health information about disorders that have a genetic component in a supportive counseling encounter. It has recently been applied in the context of psychiatric disorders (like schizophrenia, bipolar disorder, schizoaffective disorder, obsessive compulsive disorder, depression and anxiety) that typically appear sometime during later childhood through to early adulthood. Psychiatric genetic counseling is emerging as an important service that fills a growing need to reframe understandings of the causes of mental health disorders. In this review, we will define psychiatric genetic counseling, and address important ethical concerns (we will particularly give attention to the principles of autonomy, beneficence, non-maleficence and justice) that must be considered in the context of its application in adolescent psychiatry, whilst integrating evidence regarding patient outcomes from the literature. We discuss the developing capacity and autonomy of adolescents as an essential and dynamic component of genetic counseling provision in this population and discuss how traditional viewpoints regarding beneficence and non-maleficence should be considered in the unique situation of adolescents with, or at risk for, psychiatric conditions. We argue that thoughtful and tailored counseling in this setting can be done in a manner that addresses the important health needs of this population while respecting the core principles of biomedical ethics, including the ethic of care.

Mania and depression in the perinatal period among women with a history of major depressive disorders.

Women with a history of major depressive disorder (MDD) have increased risks for postpartum depression, but less is known about postpartum mania in this population. The objectives of this study were to prospectively determine the frequency with which mania occurs in the postpartum among women who have a history of MDD and to explore temporal relationships between onset of mania/hypomania and depression. We administered the Structured Clinical Interview for DSM IV disorders (SCID) to pregnant women with a self-reported history of MDD to confirm diagnosis and exclude women with any history of mania/hypomania. Participants completed the Edinburgh Postnatal Depression Scale and Altman Self-Rating Mania Scale (ASRM) once during the pregnancy (∼26 weeks) and 1 week, 1 month, and 3 months postpartum. Among women (n = 107) with a SCID-confirmed diagnosis of MDD, 34.6 % (n = 37) experienced mania/hypomania (defined by an ASRM score of ≥6) at ≥1 time point during the postpartum, and for just over half (20/37, 54 %), onset was during the postpartum. The highest frequency of mania/hypomania (26.4 %, n = 26) was at 1 week postpartum. Women who experienced mania/hypomania at 1 week postpartum had significantly more symptoms of mania/hypomania later in the postpartum. A substantive proportion of women with a history of MDD may experience first onset of mania/hypomania symptoms in the early postpartum, others may experience first onset during pregnancy. Taken with other recent data, these findings suggest a possible rationale for screening women with a history of MDD for mania/hypomania during the early postpartum period, but issues with screening instruments are discussed.

Awareness of genetic counseling and perceptions of its purpose: a survey of the Canadian public.

Genetic counseling can result in better outcomes when clients understand what to expect, and at least theoretically, at some point in their lifespan, anyone could be referred for or benefit from genetic counseling. Thus, in order to identify (and ultimately address) issues around awareness of genetic counseling and perceptions of its purpose, we surveyed the Canadian general population. We acquired 1,000 telephone numbers corresponding to a demographically representative sample of Canada from Survey Sampling International, and invited individuals to participate in a telephone-based survey. We administered a purpose-designed survey (in either French or English) comprising questions regarding: demographics, whether or not the individual had heard of genetic counseling, and 15 Likert scale-rated (strongly disagree-strongly agree) items about the possible purposes of genetic counseling. Responses to these 15 items were used to generate a total "knowledge score". Of the 1,000 numbers, n = 372 could not be reached, and the survey was successfully administered to n = 188 individuals (response rate 30 %). Most respondents (n = 129, 69 %) had not heard of genetic counseling, and substantial proportions thought that genetic counseling aims to prevent genetic diseases and abnormalities, help couples have children with desirable characteristics, and help people to understand their ancestry. These data could be used to inform the strategy for development of future awareness efforts, and as a baseline from which to measure their effects.