Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project

Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey ( β = −0.08, p = 4.2 × 10 −3 ) and white ( β = −0.13, p = 9.4 × 10 −3 ) matter superior temporal gyrus volumes, white frontal lobe volume ( β = −0.09, p = 1.5 × 10 −3 ) and the total white matter volume ( β = −0.062, p = 1.66 × 10 −2 ). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.