Ancestral, Pregnancy, and Negative Early Life Risks Shape Children's Brain Dis/Similarity to Schizophrenia.

OBJECTIVE: Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development leading to formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children.

METHODS: We used data collected by the Adolescent Brain and Cognitive Development study (ABCD; N=8,940, age=9.9±0.1 years, 4,633/4,307 M/F), including N=727 (age=9.9±0.1 years, 376/351 M/F) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, prenatal and perinatal environment, and negative early life environment. We used a Regional Vulnerability Index (RVI) to measure the alignment of a child's cerebral patterns with the adult-SSD pattern derived from a large meta-analysis of case-control differences.

RESULTS: In children with a family history of SSD, the RVI captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, RVI also captured more variance associated with negative prenatal and perinatal environment and early life experiences than traditional brain measurements.

CONCLUSIONS: In summary, in a cohort where most children will not develop SSD, familial, pre and perinatal, and early developmental risks can alter brain patterns in the direction observed in adult SSD patients. Individual similarity to adult SSD patterns may provide an early biomarker of the effects of genetic and developmental risks on the brain prior to psychotic or prodromal symptom onset.