Offspring of parents with schizophrenia, bipolar disorder, and depression: a review of familial high-risk and molecular genetics studies.

Offspring of parents with severe mental illness, including schizophrenia, bipolar disorder, and major depressive disorder, have a one-in-three risk of developing severe mental illness themselves. Over the last 60 years, three waves of familial high-risk studies examined the development of severe mental illness in offspring of affected parents. The first two waves established familial nature of schizophrenia, and demonstrated early impairment in offspring of affected parents. The most recent wave has added a focus on mood disorders and examined the transdiagnostic nature of familial risk. A synthesis of current knowledge on individuals at familial risk points to psychopathology, neurocognitive, neuroanatomical, and environmental factors involved in the familial transmission of severe mental illness. Although family history remains the single strongest predictor of illness, molecular genetic tools are becoming increasingly informative. The next decade may see family history and molecular genetics complementing each other to facilitate a transdiagnostic approach to early risk identification and prevention.