Psychiatric genetics and the structure of psychopathology

Abstract

For over a century, psychiatric disorders have been defined by expert opinion and clinical observation. The modern DSM has relied on a consensus of experts to define categorical syndromes based on clusters of symptoms and signs, and, to some extent, external validators, such as longitudinal course and response to treatment. In the absence of an established etiology, psychiatry has struggled to validate these descriptive syndromes, and to define the boundaries between disorders and between normal and pathologic variation. Recent advances in genomic research, coupled with large-scale collaborative efforts like the Psychiatric Genomics Consortium, have identified hundreds of common and rare genetic variations that contribute to a range of neuropsychiatric disorders. At the same time, they have begun to address deeper questions about the structure and classification of mental disorders: To what extent do genetic findings support or challenge our clinical nosology? Are there genetic boundaries between psychiatric and neurologic illness? Do the data support a boundary between disorder and normal variation? Is it possible to envision a nosology based on genetically informed disease mechanisms? This review provides an overview of conceptual issues and genetic findings that bear on the relationships among and boundaries between psychiatric disorders and other conditions. We highlight implications for the evolving classification of psychopathology and the challenges for clinical translation.

Etiological influences on continuity and co‐occurrence of eating disorders symptoms across adolescence and emerging adulthood

“…These results of genetic continuity carry implications for molecular genetic studies of eating disorders (Boraska et al, ; Duncan et al, ; Liu, Study, Kelsoe, & Greenwood, ) They provide preliminary support for broadening phenotypes included in molecular genetic studies to encompass a wide range of eating pathology phenotypes, to increase power to detect shared susceptibility loci (Smoller et al, ) Furthermore, given substantial stable genetic influences across adolescence and young adulthood, molecular genetic studies might not benefit from stratifying developmental samples by age. Identifying specific genes or polygenic risk scores may in turn inform precision medicine, for example, by using genetic markers to predict disease risk or treatment response.…”

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

“…In our study SZ PRS was not significantly associated with JTC. However, as PRS technique is based on contribution of common SNPs variation to genetic risk, its detection is strictly dependent on statistical power 45,46 . Although GWAS studies on schizophrenia have already identified a substantial number of genetic variants by increasing sample size 17 , SZ PRS still accounts for 7% of the variance in schizophrenia liability, as we also found in our sample.…”

Structural Brain Imaging Studies Offer Clues about the Effects of the Shared Genetic Etiology among Neuropsychiatric Disorders

“…Neuropsychiatric disorders have substantial heritability, as shown by many studies of twins and families (1). Genomewide association studies (GWAS) have shown that common genetic variants account for some of this heritability, and that some of this heritability is shared across neuropsychiatric disorders (2)(3)(4)(5). The genetic overlap across disorders may partly explain why these disorders tend to co-occur with one another in both clinical and community samples (6).…”