Neonatal Brains Express Psychiatric Risk Genes

Heightened risk for a broad range of psychiatric disorders, including schizophrenia, bipolar disorder, major depression, and autism, has been associated with several genetic variants. To ascertain at what age such polymorphisms might start affecting brain development, researchers performed magnetic resonance imaging on the brains of 144 singleton and 128 twin neonates. The researchers genotyped buccal swabs for polymorphisms on seven suspected psychiatric risk genes — disrupted in schizophrenia-1 (DISC1), catechol-O-methyltransferase (COMT), neuregulin1 (NRG1), APOE, estrogen receptor alpha (ESR1), brain-derived neurotrophic factor (BDNF), and glutamate decarboxylase-1 (GAD1). The sample was enriched for psychiatric disorder (40% of infants had a parent with a psychiatric disorder), and analyses were limited to the 70% whose mothers were white.

Several polymorphism-associated differences in brain structure were found. For example, Ser/Ser homozygotes of DISC1 had multiple areas of low volume in frontal lobes (and to lesser extents in occipital and lateral temporal lobes), and Val/Val homozygotes of COMT had multiple clusters of low volumes in temporal cortex and the right occipital and right parietal lobes. Similarly, reduced volumes in precise areas of the frontal, temporal, parietal, and occipital lobes were variously associated with specific homozygotic or heterozygotic combinations of variants of NRG1, APOE, ESR1, and BDNF. No differences were seen with GAD1 polymorphisms. Analyses controlling for parental psychiatric disorder and birthweight yielded similar results.