Psychiatric Genetic Research Research Articles

Psychiatric neuroimaging at a crossroads: Insights from psychiatric genetics

Thanks to methodological advances, large-scale data collections, and longitudinal designs, psychiatric neuroimaging is better equipped than ever to identify the neurobiological underpinnings of youth mental health problems. However, the complexity of such endeavors has become increasingly evident, as the field has been confronted by limited clinical relevance, inconsistent results, and small effect sizes. Some of these challenges parallel those historically encountered by psychiatric genetics. In past genetic research, robust findings were historically undermined by oversimplified biological hypotheses, mistaken assumptions about expectable effect sizes, replication problems, confounding by population structure, and shared biological patterns across disorders. Overcoming these challenges has contributed to current successes in the field. Drawing parallels across psychiatric genetics and neuroimaging, we identify key shared challenges as well as pinpoint relevant insights that could be gained in psychiatric neuroimaging from the transition that occurred from the candidate gene to (post) genome-wide “eras” of psychiatric genetics. Finally, we discuss the prominent developmental component of psychiatric neuroimaging and how that might be informed by epidemiological and omics approaches. The evolution of psychiatric genetic research offers valuable insights that may expedite the resolution of key challenges in psychiatric neuroimaging, thus potentially moving our understanding of psychiatric pathophysiology forward.

Applying an ELSI lens to real-world data and novel genomic insights for personalized mental healthcare.

Improving the understanding of the complex relationship between genetic predispositions, environmental influences, and sociocultural factors in the development and progression of mental illness is crucial for optimizing treatment efficacy and addressing longstanding health disparities. This paper discusses the ethical, legal, and social implications (ELSI) of recent advancements in biomedical research, particularly in genome-wide association studies (GWAS), phenome-wide association studies (PheWAS), and genome-wide environment interaction studies (GWEIS). Despite recent scientific progresses, challenges such as inadequate study methodology (e.g., correlational studies) and lack of diversity within study samples persist. Recent discoveries of several genetic variants of diseases, could augment and improve, or even challenge, existing understanding of the onset and management of mental illness. Leveraging real-world data (RWD), including electronic health record data (EHRs) focused on social determinant of health alongside biobank data, offers further opportunities to enhance the understanding of gene-environment interactions and inform efforts for reducing disparities in mental healthcare. Increased knowledge can support timely, holistic, evidence-based, and personalized care. Addressing ELSI considerations and maximizing the use of RWD is essential for advancing ethical and inclusive psychiatric genetics research, ultimately improving patient outcomes and promoting equitable access to evidence-based treatments.

Prevalence and correlates of common mental disorders among participants of the Uganda Genome Resource: Opportunities for psychiatric genetics research.

Genetics research has potential to alleviate the burden of mental disorders in low- and middle-income-countries through identification of new mechanistic pathways which can lead to efficacious drugs or new drug targets. However, there is currently limited genetics data from Africa. The Uganda Genome Resource provides opportunity for psychiatric genetics research among underrepresented people from Africa. We aimed at determining the prevalence and correlates of major depressive disorder (MDD), suicidality, post-traumatic stress disorder (PTSD), alcohol abuse, generalised anxiety disorder (GAD) and probable attention-deficit hyperactivity disorder (ADHD) among participants of the Uganda Genome Resource. Standardised tools assessed for each mental disorder. Prevalence of each disorder was calculated with 95% confidence intervals. Multivariate logistic regression models evaluated the association between each mental disorder and associated demographic and clinical factors. Among 985 participants, prevalence of the disorders were: current MDD 19.3%, life-time MDD 23.3%, suicidality 10.6%, PTSD 3.1%, alcohol abuse 5.7%, GAD 12.9% and probable ADHD 9.2%. This is the first study to determine the prevalence of probable ADHD among adult Ugandans from a general population. We found significant association between sex and alcohol abuse (adjusted odds ratio [AOR] = 0.26 [0.14,0.45], p < 0.001) and GAD (AOR = 1.78 [1.09,2.49], p = 0.019) respectively. We also found significant association between body mass index and suicidality (AOR = 0.85 [0.73,0.99], p = 0.041), alcohol abuse (AOR = 0.86 [0.78,0.94], p = 0.003) and GAD (AOR = 0.93 [0.87,0.98], p = 0.008) respectively. We also found a significant association between high blood pressure and life-time MDD (AOR = 2.87 [1.08,7.66], p = 0.035) and probable ADHD (AOR = 1.99 [1.00,3.97], p = 0.050) respectively. We also found a statistically significant association between tobacco smoking and alcohol abuse (AOR = 3.2 [1.56,6.67], p = 0.002). We also found ever been married to be a risk factor for probable ADHD (AOR = 2.12 [0.88,5.14], p = 0.049). The Uganda Genome Resource presents opportunity for psychiatric genetics research among underrepresented people from Africa.

Bruno Schulz's 1936 book "Methodology of medical genetic research particularly with regard to psychiatry".

In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk. For the field work, Schulz emphasizes the importance of trust-building, confidentiality, collateral informants, and the use of medical and other administrative records, all ideally stored in personal files. Several methods of age-correction are reviewed. Schulz provides detailed algebraic treatments of these and other problems, including tests for etiologic homogeneity, with worked examples. He emphasizes two fundamental concerns in psychiatric genetics research: (i) its inter-dependency with the optimal diagnostic boundaries, which are rarely known and (ii) the genetic homogeneity of clinical samples. Given these problems, he is pessimistic about finding Mendelian transmission patterns. He assesses the predominant 19th-century method of psychiatric genetic investigation-"hereditary burden"-to be crude and biased by family size. Although written at a time of consolidation of Nazi power in Germany, this book nowhere endorses their racial/eugenic policies and can be seen as subtly questioning them.

Systematic exploration of a decade of publications on psychiatric genetics in Latin America.

Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene-environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.

The examination of Kraepelin's diagnoses of dementia praecox and manic-depressive insanity in pedigrees: Studies of Schuppius in 1912 and Wittermann in 1913.

In the first two decades of the 20th century, a new approach to psychiatric genetics research emerged in Germany from three roots: (i) the wide-spread acceptance of Kraepelin's diagnostic system, (ii) increasing interest in pedigree research, and (iii) excitement about Mendelian models. We review two relevant papers, reporting analyses of, respectively, 62 and 81 pedigrees: S. Schuppius in 1912 and E. Wittermann in 1913. While most prior asylum based studies only reported a patient's "hereditary burden," they examined diagnoses of individual relatives at a particular place in a pedigree. Both authors focused on the segregation of dementia praecox (DP) and manic-depressive insanity (MDI). Schuppius reported that the two disorders frequently co-occurred in his pedigrees while Wittermann found them to be largely independent. Schuppius was skeptical of the feasibility of evaluating Mendelian models in humans. Wittermann, by contrast, with advice from Wilhelm Weinberg, applied algebraic models with proband correction to DP in his sibships with results consistent with autosomal recessive transmission. While he had less data, Wittermann suggested that MDI was likely an autosomal dominant disorder. Both authors were interested in other disorders or traits appearing in pedigrees dense with DP (e.g., idiocy) or MDI (e.g., highly excitable individuals).

Influences of race and clinical variables on psychiatric genetic research participation: Results from a schizophrenia sample.

Advances in genetics has led to a better understanding of both genetic and environmental contributions to psychiatric mental health disorders. But psychiatric genetics research is predominantly Eurocentric, and individuals of non-European ancestry continue to be significantly underrepresented in research studies with potential to worsen existing mental health disparities. The objective of this study was to examine factors associated with genetic study participation in a schizophrenia sample. The study sample was extracted from the Clinical Antipsychotics Trial of Intervention Effectiveness (CATIE) schizophrenia study which enrolled 1493 patients with chronic schizophrenia between the ages of 18-65 years and incorporated an optional genetic sub-study. Using a logistic regression model (N = 1249), we examined sociodemographic and clinical variables that were independently associated with the outcome i.e., participation in the genetic sub-study. The genetic sub-study had a lower proportion of Black (30% in genetic vs 40% in CATIE overall) and other race (4% vs 6%) participants. Increased severity of psychopathology symptoms (odds ratio [OR] = 0.78, p = 0.004) decreased the odds whereas better reasoning scores (OR = 1.16, p = 0.036) increased the odds of genetic study participation. Compared to Black participants, White participants were significantly more likely to participate in the genetic sub-study (OR = 1.43, p = 0.009). Clinical factors in addition to race significantly impact genetic study participation of individuals with chronic schizophrenia. Our findings highlight the need for future research that examines the interactive effects of race and clinical factors such as symptom severity on psychiatrically ill individuals' choice to participate in genetics studies and to identify targeted strategies to increase equitable representation in psychiatric genetics research.

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications.

Psychiatric genetics has made substantial progress in the last decade, providing new insights into the genetic etiology of psychiatric disorders, and paving the way for precision psychiatry, in which individual genetic profiles may be used to personalize risk assessment and inform clinical decision-making. Long recognized to be heritable, recent evidence shows that psychiatric disorders are influenced by thousands of genetic variants acting together. Most of these variants are commonly occurring, meaning that every individual has a genetic risk to each psychiatric disorder, from low to high. A series of large-scale genetic studies have discovered an increasing number of common and rare genetic variants robustly associated with major psychiatric disorders. The most convincing biological interpretation of the genetic findings implicates altered synaptic function in autism spectrum disorder and schizophrenia. However, the mechanistic understanding is still incomplete. In line with their extensive clinical and epidemiological overlap, psychiatric disorders appear to exist on genetic continua and share a large degree of genetic risk with one another. This provides further support to the notion that current psychiatric diagnoses do not represent distinct pathogenic entities, which may inform ongoing attempts to reconceptualize psychiatric nosology. Psychiatric disorders also share genetic influences with a range of behavioral and somatic traits and diseases, including brain structures, cognitive function, immunological phenotypes and cardiovascular disease, suggesting shared genetic etiology of potential clinical importance. Current polygenic risk score tools, which predict individual genetic susceptibility to illness, do not yet provide clinically actionable information. However, their precision is likely to improve in the coming years, and they may eventually become part of clinical practice, stressing the need to educate clinicians and patients about their potential use and misuse. This review discusses key recent insights from psychiatric genetics and their possible clinical applications, and suggests future directions.

Influences of race and clinical variables on psychiatric genetic research participation: Results from a schizophrenia sample

Influences of race and clinical variables on psychiatric genetic research participation: Results from a schizophrenia sample

Introduction to "The Beginnings of Systematic Studies of the Genetics of Schizophrenia: 1916-1933".

We here want to introduce this special issue of Schizophrenia Bulletin by providing some background about the history of psychiatric genetics before 1910, the choice of the 5 papers here examined, the methodology we used in writing these papers, the relevance for contemporary psychiatric genetics and a background on our approach to the relationship of the authors of these papers to the eugenic, racist policies of the German National Socialists that led to the large-scale involuntary sterilization of the mentally ill, and the K-4 program of wide-scale murder of mentally ill and handicapped children and adults and the Holocaust. We recommend that interested individuals read the 5 papers in order as this will help them see the historical progression of the methods and results in this early phase of psychiatric genetics research. To appreciate the papers reviewed in this special issue, it is helpful to understand the status of the field of psychiatric genetics circa 1910, before the first important papers based on the rediscovery of Mendel’s work in 1900. K.S.K. has recently written a review paper covering this literature “The Pre-History of Psychiatric Genetics: 1780-1910”,1 which can be consulted by readers interested in this topic. Briefly, in the 19th century, far and away the most common data point used in the psychiatric genetic investigation was a statement in an asylum record of the presence or absence of a “hereditary burden” for the patient, a term broadly congruent with what we might now call a “positive family history.” However, its use was complicated by the fact that across different hospitals, different groups of relatives were included (eg, direct ancestors only, eg, parents and grandparents or direct + collateral including aunts/uncles and potentially siblings), and different conditions were considered as affected (narrowly defined insanity, more broadly defined mental illness, alcoholism, eccentricities, epilepsy, etc.). Few of these relatives were ever personally examined by the alienist recording this information. Common topics of interest at that time included the relationship between a heredity burden and the sex of the patient, the recurrence of episodes of insanity, and the degree of homogeneity versus heterogeneity of transmission of mental illnesses in families.1,2 No formal theories of hereditary transmission were ever examined as the first detailed application of both the biometrical school of Galton and Pearson and Mendelian theory to insanity were not published until the first and second decades of the 20th century.3–8

Ludvig Dahl's psychiatric genetic studies in his 1859 monograph: "Contribution to the knowledge of insanity in Norway".

In 1859, Ludvig Dahl, a Norwegian alienist, wrote a rarely referenced book entitled "Contribution to The Knowledge of Insanity." In it, he describes a highly innovative psychiatric genetics research project with severable notable features. First, while the vast majority of 19th century psychiatric genetic studies were based on asylum hospital records, Dahl did field work to find cases of mental illness in certain defined areas within Norway, using census data, key-informants, record reviews, and personal interviews especially of suspected affected individuals. Second, for the first time in the history of psychiatric genetics, and perhaps more broadly in medical genetics, Dahl studied and graphed extensive pedigrees covering up to seven generations demonstrating a high density of psychiatric illness. Third, he proposed and conducted the first controlled investigation of familial aggregation of insanity. A 126 member 5-generation pedigree that he studied contained 8 individuals with confirmed insanity compared to 16 cases in the remaining 2,974 individuals in the Parish, a relative risk of nearly 12. Dahl also noted the co-segregation within pedigrees of mental handicap, deaf-mutism, and insanity. He evaluated familial-environmental sources of familial aggregation and noted, among nonpsychotic family members in his pedigrees, personalities that might reflect a "disposition" to insanity.

W57. MENTAL HEALTH DATA COLLECTION IN THE ESTONIAN BIOBANK: INSTRUMENTS, METHODOLOGY AND PRELIMINARY RESULTS

Background: Background: Common psychiatric disorders are clinically heterogeneous and often display many overlapping symptoms as well as comorbidity across psychiatric disorders, hence complicating the genetic investigation of these disorders. To facilitate new discoveries and gain better understanding of the genetics of psychiatric problems, large well-phenotyped biobank samples are greatly needed. The Estonian Biobank (EstBB;N=200,000) is a data-rich national biobank that joins genomic, biomarker, electronic health record (EHR), national registry and questionnaire data to significantly advance the current knowledge of the genetic underpinnings of complex and rare diseases. We aimed to expand the EstBB database with rich phenotypic questionnaire-based information on a broad set of symptoms of common psychiatric disorders and related phenotypes. Methods: Methods: We compiled an online questionnaire “Wellbeing and mental health” which included self-report brief screening instruments to capture a broad range of symptoms on current and/or lifetime depression, anxiety disorders, mania, post-traumatic stress disorder, eating disorders, attention deficit/hyperactivity disorder, psychotic experiences, suicidal thoughts and behavior, cognition, substance (ab)use, problematic gambling and related risk- and protective factors, such as childhood adversity, stressful life events, social support, lifestyle, sociodemographic factors and life satisfaction. In addition, the participants were asked about the side effects, discontinuation and switching of medications prescribed for a mental health problem in their lifetime. Since the start of the data collection coincided with the peak of the second COVID-19 wave in Estonia, we included items related to current perceived stress, burnout and change in mental health during the pandemic. When selecting instruments, preference was given based on 1) reliability and validity of the instruments;2) whether an Estonian adaptation and/or validation has been conducted;3) application in other large biobanks (e.g. the UK Biobank) for future harmonization or replication;4) short length. Results: Results: The invitations to participate in the online mental health study were e-mailed out to all living EstBB participants with available e-mail addresses (N=184,622), followed by two e-mail reminders. The active data collection phase spanned over three months from March to May 2021. The preliminary response rate was 46.7% (N = 86,222) out of all who were contacted. We will present preliminary results on the comparison of respondents and non-respondents based on demographic data, psychiatric diagnoses in EHR and psychiatric polygenic risk scores. Discussion: Discussion: We have significantly expanded the EstBB resource with phenotypic information on a broad range of psychiatric symptoms and related phenotypes to facilitate future research in psychiatric genetics. Disclosure: Nothing to disclose.

Ernst Rüdin's, 1911 vision of a Mendelian psychiatric genetics research program: His paper "Methods and goals of family research in psychiatry".

While working under Kraepelin in Munich, Ernst Rüdin, a Swiss-born Psychiatrist, at the age of 26, outlined in a 1911 98-page article, a detailed plan for a future Mendelian-informed family research program for psychiatry. Rüdin would go on to head the Department of Genealogical and Demographic Studies at Kraepelin's Research Institute which became one of the world's leading programs in psychiatric genetics. I here summarize this article, providing a complete translation online. Rüdin's review outlined a paradigm shift in psychiatric genetics research moving from calculations of aggregate hereditary burden, as they applied to the proband, to examining patterns of transmission within family pedigrees which involved careful individual assessments of relatives. He references widely clinical and statistical genetic studies, many focusing on the newly discovered Mendelian laws. However, Rüdin was no genetic reductionist but recognized the contribution of environmental risk factors to psychiatric illness arguing that they should be studied as part of a comprehensive research program. As a committed eugenicist, Rüdin also explored the implications of such a program for "racial hygiene." Rüdin's contributions should be viewed in the context of his extensive collaboration from 1933 to 1945 with the National Socialists and his support for their eugenics program, including involuntary sterilizations.

The nature of hereditary influences on insanity from research on asylum records in Western Europe in the mid-19th century.

This article explores the nature of psychiatric genetics research conducted in asylums in Western Europe in the mid-19th century through an examination of four studies published 1841 to 1864 from Great Britain, France, and Germany. They all utilize asylum records to determine if patients had a hereditary predisposition (HP) to mental illness. A diverse range of topics were investigated, with most attention on whether men or women are more likely to transmit, or are more sensitive to the receipt of, an HP. When significant sex effects were seen, they consistently found women to be more likely to transmit and/or more sensitive to the receipt of an HP. Other questions explored included: (a) the relationship between an HP and recurrence rates; (b) the degree of homogeneity versus heterogeneity of transmission of specific mental illnesses in families; (c) the level of HP among different forms of mental illness; and (d) differences in the proportion of psychiatric patients with an HP as a function of their religion. While the method of assessment of familial/genetic risk was relatively crude, even at this early stage in the history of psychiatric genetics, investigators were asking thoughtful questions about the nature and clinical impact of that risk.

Genome-wide association study accounting for anticholinergic burden to examine cognitive dysfunction in psychotic disorders.

Identifying genetic contributors to cognitive impairments in psychosis-spectrum disorders can advance understanding of disease pathophysiology. Although CNS medications are known to affect cognitive performance, they are often not accounted for in genetic association studies. In this study, we performed a genome-wide association study (GWAS) of global cognitive performance, measured as composite z-scores from the Brief Assessment of Cognition in Schizophrenia (BACS), in persons with psychotic disorders and controls (N = 817; 682 cases and 135 controls) from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Analyses accounting for anticholinergic exposures from both psychiatric and non-psychiatric medications revealed five significantly associated variants located at the chromosome 3p21.1 locus, with the top SNP rs1076425 in the inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1) gene (P = 3.25×E-9). The inclusion of anticholinergic burden improved association models (P < 0.001) and the number of significant SNPs identified. The effect sizes and direction of effect of the top variants remained consistent when investigating findings within individuals receiving specific antipsychotic drugs and after accounting for antipsychotic dose. These associations were replicated in a separate study sample of untreated first-episode psychosis. The chromosome 3p21.1 locus was previously reported to have association with the risk for psychotic disorders and cognitive performance in healthy individuals. Our findings suggest that this region may be a psychosis risk locus that is associated with cognitive mechanisms. Our data highlight the general point that the inclusion of medication exposure information may improve the detection of gene-cognition associations in psychiatric genetic research.

Return of results in a global survey of psychiatric genetics researchers: practices, attitudes, and knowledge

PurposePatient-participants in psychiatric genetics research may be at an increased risk for negative psychosocial impacts related to the return of genetic research results. Examining psychiatric genetics researchers’ return of results practices and perspectives can aid the development of empirically informed and ethically sound guidelines. MethodsA survey of 407 psychiatric genetics researchers from 39 countries was conducted to examine current return of results practices, attitudes, and knowledge. ResultsMost respondents (61%) reported that their studies generated medically relevant genomic findings. Although 24% have returned results to individual participants, 52% of those involved in decisions about return of results plan to return or continue to return results. Respondents supported offering “medically actionable” results related to psychiatric disorders (82%), and the majority agreed non–medically actionable risks for Huntington (71%) and Alzheimer disease (64%) should be offered. About half (49%) of respondents supported offering reliable polygenic risk scores for psychiatric conditions. Despite plans to return, only 14% of researchers agreed there are adequate guidelines for returning results, and 59% rated their knowledge about how to manage the process for returning results as poor. ConclusionPsychiatric genetics researchers support returning a wide range of results to patient-participants, but they lack adequate knowledge and guidelines.

Polygenic Scores for ADHD: A Meta-Analysis.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that is known to have a polygenic (i.e., many genes of individually small effects) architecture. Polygenic scores (PGS), which characterize this polygenicity as a single score for a given individual, are considered the state-of-the-art in psychiatric genetics research. Despite the proliferation of ADHD studies adopting this approach and its clinical implications, remarkably little is known about the predictive utility of PGS in ADHD research to date, given that there have not yet been any systematic or meta-analytic reviews of this rapidly developing literature. We meta-analyzed 12 unique effect sizes from ADHD PGS studies, yielding an N = 40,088. These studies, which included a mixture of large population-based cohorts and case-control samples of predominantly European ancestry, yielded a pooled ADHD PGS effect size of rrandom = 0.201 (95% CI = [0.144, 0.288]) and an rfixed = 0.190 (95% CI = [0.180, 0.199]) in predicting ADHD. In other words, ADHD PGS reliably account for between 3.6% (in the fixed effects model) to 4.0% (in the random effects model) of the variance in broadly defined phenotypic ADHD. Findings provide important insights into the genetics of psychiatric outcomes and raise several key questions about the impact of PGS on psychiatric research moving forward. Our review concludes by providing recommendations for future research directions in the use of PGS, including new methods to account for comorbidities, integrating bioinformatics to elucidate biological pathways, and leveraging PGS to test mechanistic models of ADHD.

Eliciting Willingness and Beliefs towards Participation in Genetic Psychiatric Testing in Black/African American Mothers at Risk for Depression.

Black/African American women are at high risk for depression, yet are underrepresented in psychiatric genetic research for depression prevention and treatment. Little is known about the factors that influence participation in genetic testing for Black/African American women at risk. The purpose of this study was to elicit the beliefs that underlie participation in genetic testing for depression in Black/African American mothers, a subgroup at high risk. Willingness to participate in genetic testing procedures was also determined. A qualitative, descriptive design was employed. Exactly 19 mothers aged 21–42 completed open-ended questionnaires. Directed content and descriptive analyses of the text were conducted based on the Theory of Planned Behavior. Salient beliefs included: behavioral advantages—diagnosing/detecting depression (31.6%), finding cure/treatment (21.1%); disadvantages—not finding follow-up treatment/help (21.1%); salient referents, who approves—family members (47.4%), agencies/organizations (26.3%); who disapproves—church associates (21.1%). Control beliefs included: barriers—unpleasant/difficult testing procedures (42.1%), limited knowledge about the purpose of testing (26.3%); facilitator—a convenient location (21.1%). Most mothers (89.5%) indicated willingness to participate in testing. Interventions can target families, address barriers, emphasize future benefits, and use convenient locations and community-based participatory research methods. Policies can address social determinants of participation to increase inclusion of these mothers in psychiatric genetic research.

Perceptions of best practices for return of results in an international survey of psychiatric genetics researchers.

Many research sponsors and genetic researchers agree that some medically relevant genetic findings should be offered to participants. The scarcity of research specific to returning genetic results related to psychiatric disorders hinders the ability to develop ethically justified and empirically informed guidelines for responsible return of results for these conditions. We surveyed 407 psychiatric genetics researchers from 39 countries to examine their perceptions of challenges to returning individual results and views about best practices for the process of offering and returning results. Most researchers believed that disclosure of results should be delayed if a patient-participant is experiencing significant psychiatric symptoms. Respondents felt that there is little research on the impact of returning results to participants with psychiatric disorders and agreed that return of psychiatric genetics results to patient-participants may lead to discrimination by insurance companies or other third parties. Almost half of researchers believed results should be returned through a participant’s treating psychiatrist, but many felt that clinicians lack knowledge about how to manage genetic research results. Most researchers thought results should be disclosed by genetic counselors or medical geneticists and in person; however, almost half also supported disclosure via telemedicine. This is the first global survey to examine the perspectives of researchers with experience working with this patient population and with these conditions. Their perspectives can help inform the development of much-needed guidelines to promote responsible return of results related to psychiatric conditions to patients with psychiatric disorders.

The search for personalized antidepressant treatments: what have we learned and where are we going.

Over 20years after the initial report of gene variants within the central nervous system modulating antidepressant response, we are now facing for the first time routine clinical pharmacogenetic applications. The scientific community is divided between enthusiasm and skepticism. It seems clear that the benefit of existing tools is not huge, at least for the central nervous systemgene variants, while it is generally accepted for the metabolic gene variants. Findings from large international consortia suggest for the first time in psychiatric genetic research history that cumulative scores comprising many variants across the whole genome may reliably constitute liability factors for psychiatric disorders, this approach will most likely improve also present pharmacogenetic tools. A composite genetic score complemented with clinical risk factors for each patient is the most promising approach for a more effective method of targeted treatment for patients with depression.