Ancestral, Pregnancy, and Negative Early-Life Risks Shape Children's Brain (Dis)similarity to Schizophrenia

Peter Kochunov, Yizhou Ma, Kathryn S. Hatch, Si Gao, Ashley Acheson, Neda Jahanshad, Paul M. Thompson, Bhim M. Adhikari, Heather Bruce, Andrew Van der vaart, Joshua Chiappelli, Xiaoming Du, Aris Sotiras, Mark D. Kvarta, Tianzhou Ma, Shuo Chen, L. Elliot Hong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the 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 Cognitive Development (ABCD) Study (N = 8940, age = 9.9 ± 0.1 years, 4307/4633 female/male), including 727 (age = 9.9 ± 0.1 years, 351/376 female/male) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, pre/perinatal environment, and negative early-life environment. We used a regional vulnerability index 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 regional vulnerability index captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, the regional vulnerability index also captured more variance associated with negative pre/perinatal environment and early-life experiences than traditional brain measurements. Conclusions: In summary, in a cohort in which most children will not develop SSD, familial, pre/perinatal, and early developmental risks can alter brain patterns in the direction observed in adult patients with SSD. 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.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalBiological Psychiatry
Issue number4
StatePublished - Aug 15 2023


  • Adolescence
  • Big data
  • Brain development
  • Imaging
  • Individual prediction
  • Schizophrenia


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