The human Clock gene has been proposed as a possible candidate for disorders affected by alterations of circadian rhythm, including bipolar disorder and schizophrenia.
This preliminary observation leads to hypothesize a role for the CLOCK gene polymorphism in the regulation of long-term illness recurrence in bipolar disorder.
One of the human circadian clock genes, cryptochrome 1 (Cry1) (located on 12q23-q24.1) was analyzed because of its close correspondence to a linkage hotspot for bipolar disorder.
We have assessed evidence for linkage and association involving polymorphisms in 10 circadian clock genes (ARNTL, CLOCK, CRY2, CSNK1epsilon, DBP, GSK3beta, NPAS2, PER1, PER2, and PER3) to BPAD.
We had previously identified the clock gene D-box binding protein (Dbp) as a potential candidate gene for bipolar disorder and for alcoholism, using a Convergent Functional Genomics (CFG) approach.
A multi-locus interaction between rs6442925 in the 5' upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3' end of the CLOCK gene, however, is significantly associated with BP (P = 0.00000172).
We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder.
This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder.
The clock gene (CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study.
We determined genotype for 16 variants in seven circadian clock genes and conducted a candidate gene association study of these in 282 Caucasian patients with BD who were previously treated with lithium.
Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies.
Previously, we found correlations between lithium efficacy in bipolar disorder and temperamental dimensions of the TEMPS-A and also genes involved in the regulation of biological rhythms ("clock" genes).
Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses.
Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses.