|Authors||Gleason G, Liu B, Bruening S, Zupan B, Auerbach A, Mark W, Oh JE, Gal-Toth J, Lee F, Toth M|
|Journal||Proc. Natl. Acad. Sci. U.S.A. Volume: 107 Issue: 16 Pages: 7592-7|
|Publish Date||2010 Apr 20|
Low serotonin(1A) receptor (5-HTR) binding is a risk factor for anxiety and depression, and deletion of the 5-HTR results in anxiety-like behavior in mice. Here we show that anxiety-like behavior in mice also can be caused, independently of the offspring’s own 5-HTR genotype, by a receptor deficit in the mother: a nongenetic transmission of a genetic defect. Some of the nongenetically transmitted anxiety manifestations were acquired prenatally and linked to a delay in dentate gyrus maturation in the ventral hippocampus of the offspring. Both the developmental delay and the anxiety-like phenotype were phenocopied by the genetic inactivation of p16(ink4a) encoding a cyclin-dependent kinase inhibitor implicated in neuronal precursor differentiation. No maternal 5-HTR genotype-dependent anxiety developed when the strain background was switched from Swiss Webster to C57BL/6, consistent with the increased resilience of this strain to early adverse environment. Instead, all anxiety manifestations were caused by the offspring’s own receptor deficiency, indicating that the genetic and nongenetic effects converge to common anxiety manifestations. We propose that 5-HTR deficit represents a dual risk for anxiety and that vulnerability to anxiety associated with genetic 5-HTR deficiency can be transmitted by both genetic and nongenetic mechanisms in a population. Thus, the overall effect of risk alleles can be higher than estimated by traditional genetic assays and may contribute to the relatively high heritability of anxiety and psychiatric disorders in general.
|Full Text||Full text available on PubMed Central|