Gene–environment interplay in the etiology of psychosis

Abstract

Schizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene-environment interactions. Only a few specific gene-environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene-environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

Neurodevelopmental and genetic determinants of exposure to adversity among youth at risk for mental illness

“…Our findings represent an example of a gene–environment correlation, which occurs when genetic and environmental factors contributing to psychopathology are associated (Plomin, DeFries, & Loehlin, ; Zwicker, Denovan‐Wright, & Uher, ). Based on our results, we can speculate about the mechanisms through which genetic liability to ADHD may contribute to exposure to adversity.…”

Genetic Risk of Psychosis in Relation to Cannabis Use: Findings from Polygenic Risk Score Approaches

“…This has been consistently reported in several longitudinal cohorts [12][13][14][15][16]. On the other hand, some studies have described the possibility that psychosis may lead to an increased propensity to cannabis use, and especially people with psychotic spectrum disorders are more likely to experiment with drugs [17][18][19][20].…”

“…In the future, larger sample sizes will be necessary to investigate the genetic association between a mental disorder and cannabis use and to identify common genes and biological mechanisms that may explain this association. Moreover, in a different but complementary approach, the enormous technical progress in the field of genomic high-throughput technologies (next generation sequencing) will probably lead to new insights into the influence of rare variants (low frequency) in the coming years; first molecular genetic studies have already shown that common and rare variants contribute to the genetic risk for psychosis [18].…”

Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness

“…12 This sensitive period of neurodevel opment overlaps with the timing of the most prominent environ mental risk factors associated with psychosis. 13 Large multisite neuroimaging studies have found reduc tions in cortical folding among adults with psychotic disor ders. 14,15 Aberrant gyrification has also been reported in people at genetic risk for schizophrenia.…”