An epigenetic, transgenerational model of increased mental health disorders in children, adolescents and young adults.

Prevalence rates of mental health disorders in children and adolescents have increased two to threefold from the 1990s to 2016. Some increase in prevalence may stem from changing environmental conditions in the current generation which interact with genes and inherited genetic variants. Current measured genetic variant effects do not explain fully the familial clustering and high heritability estimates in the population. Another model considers environmental conditions shifting in the previous generation, which altered brain circuits epigenetically and were transmitted to offspring via non-DNA-based mechanisms (intergenerational and transgenerational effects). Parental substance use, poor diet and obesity are environmental factors with known epigenetic intergenerational and transgenerational effects, that regulate set points in brain pathways integrating sensory-motor, reward and feeding behaviors. Using summary statistics for eleven neuropsychiatric and three metabolic disorders from 128,989 families, an epigenetic effect explains more of the estimated heritability when a portion of parental environmental effects are transmitted to offspring alongside additive genetic variance.