Dysregulation of peripheral expression of the YWHA genes during conversion to psychosis

The seven human 14-3-3 proteins are encoded by the YWHA-gene family. They are expressed in the brain where they play multiple roles including the modulation of synaptic plasticity and neuronal development. Previous studies have provided arguments for their involvement in schizophrenia, but their role during disease onset is unknown. We explored the peripheral-blood expression level of the seven YWHA genes in 92 young individuals at ultra-high risk for psychosis (UHR). During the study, 36 participants converted to psychosis (converters) while 56 did not (non-converters). YWHA genes expression was evaluated at baseline and after a mean follow-up of 10.3 months using multiplex quantitative PCR. Compared with non-converters, the converters had a significantly higher baseline expression levels for 5 YWHA family genes, and significantly different longitudinal changes in the expression of YWHAE, YWHAG, YWHAH, YWHAS and YWAHZ. A principal-component analysis also indicated that the YWHA expression was significantly different between converters and non-converters suggesting a dysregulation of the YWHA co-expression network. Although these results were obtained from peripheral blood which indirectly reflects brain chemistry, they indicate that this gene family may play a role in psychosis onset, opening the way to the identification of prognostic biomarkers or new drug targets.