FBXL3 is part of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase complex that binds and leads to phosphorylation-dependent degradation of the central clock protein cryptochromes (CRY1 and CRY2) by the proteasome and its absence causes circadian phenotypes in mice and behavioral problems.
Literature suggests that the CLOCK gene exerts important influence on these conditions, and influences the susceptibility to phenotypes of psychiatric disorders.
The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders).
In addition, hCLOCK expression is affected by glucocorticoids, consistent with the sex-dependency of the genetic associations and the modulation of glucocorticoid-mediated stress response, providing a mechanism by which the circadian clock controls outputs that may affect psychiatric disorders.
Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of P < 0.05, and none of the the variants identified in candidate studies of clock genes that were included in the PGC datasets were significant after correction for multiple testing.
Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders.
Specifically, because clock gene dysfunction is good candidate for enhancing the susceptibility to these psychiatric disorders, we selected two circadian rhythm-related genes (CSNK1D and CSNK1E) and investigated genetic associations of the genes with these three disorders.