Childhood Stress and Schizophrenia Risk: A Genetic Link

Barbara Geller, MD

In a study in mice, prepubertal stress is associated with changes in gene expression.

Stress during childhood has been linked to later schizophrenia in some individuals, but the roles of genotype and gene expression in this association have been less understood. These researchers aimed to obtain preclinical evidence of the relationship between prepuberty stress and previously identified schizophrenia risk genes.

At postnatal days 25 through 27 (corresponding to human prepuberty), mice underwent acute stress paradigms that included forced swim, restraint stress, and foot shocks. In behavioral and gene-expression tests in the hippocampus given on postnatal day 60, stressed mice compared with nonstressed controls had higher anxiety on the elevated plus maze test and greater Disc1 expression and lower messenger RNA in Gsk3β and Nrg1 (type III).

In another experiment, mice underwent the same stress paradigms, with gene expression measured at 24 hours prior to stress paradigms and at 24 hours and 7 days afterwards. No changes occurred from baseline to 24 hours post-stress. At day 7, stress was associated with altered expression of Disc1 and, in males only, Nrg1 (type 1).

CITATION(S):

Brydges NM et al. Juvenile stress produces long-lasting changes in hippocampal DISC1, GSK3ß and NRG1 expression. Mol Psychiatry 2014 Jan 28; [e-pub ahead of print].