Genetics for mental health clinicians: a call for a globally accessible and equitable psychiatric genetics education

Abstract

The field of psychiatric genetics has evolved rapidly over the past decades, leading to major advancements in our understanding of the genetic architecture of mental disorders. Dozens of genes have been definitively linked to neurodevelopmental disorders (NDDs), and hundreds of genetic loci have been significantly associated with psychiatric diseases and/or traits (e.g., schizophrenia, neuroticism), potentially shining light on underlying biological disease processes and possible routes for targeted treatment 1 . Despite this progress, psychiatric genetics education for mental health clinicians remains fragmented and inconsistent across the globe 2 , which has major implications for the quality of care that patients receive and the ability of mental health professionals to effectively incorporate genetics into clinical practice. First and foremost, basic counseling about the genetic component of the etiology of many mental disorders – as part of the broader psychoeducation mission – can help reduce stigma, guilt and misunderstanding about what mental illness is3. It can help families and patients focus on identifying resilience factors to counteract genetic risk, such as improved sleep, diet and exercise 3 . Effective counseling can be provided in almost any setting without additional resources or technologies. A genetic diagnosis can be made in 25‐40% of patients with NDDs4. For this patient population, genetic diagnoses have well‐established clinical benefits, such as ending the diagnostic odyssey that many families face, informing family planning, enhancing prognostic counseling, offering the opportunity for earlier intervention to support neurodevelopment, and providing access to relevant clinical trials and support networks of other families with similar genetic conditions 4 . Furthermore, with the advancement of precision genetic therapies, there is now the possibility of disease‐modifying treatment for NDDs. Mental health clinicians should also understand the basic principles of pharmacogenetics (e.g., how an individual's genetic make‐up affects his/her response to medications). Pharmacogenetic testing may allow for the selection of psychiatric medications that have fewer side effects 5 . For instance, pharmacogenetic testing for HLA class I variants can prevent serious cutaneous adverse reactions (e.g., Stevens‐Johnson syndrome, toxic epidermal necrolysis) in individuals starting on carbamazepine or oxcarbazepine 5 . Moreover, a recent controlled, cluster‐randomized crossover study demonstrated that a 12‐gene pharmacogenetic panel (including the liver enzyme cytochrome P450 genes, CYP2D6 and CYP2C19, which are responsible for the metabolism of most psychotropic medications) reduced the incidence of adverse drug reactions across diverse European health‐care system organizations and settings 6 . Given the relatively low cost of pharmacogenetic testing and the high burden of adverse psychotropic drug effects, global implementation is plausible. Widespread psychiatric pharmacogenetic education can prepare mental health workforces to implement pharmacogenetic testing more rapidly and efficiently as access grows. However, education initiatives will need to emphasize the large variation in allele frequency of pharmacogenes between populations of difference ancestries, to ensure that clinical approaches are tailored accordingly 6 . Moreover, although not yet rigorously validated for clinical use in mental disorders, polygenic risk scores (PGS) have great potential as a future tool in psychiatric care 7 . A PGS is a measure that represents the combined effects of many common genetic variants associated with a complex trait or disease 7 . In psychiatry, PGS are being explored on their own and in combination with other risk factors as predictors of disease onset, such as schizophrenia in a population at high risk for psychosis 7 . Despite the need for ongoing resear