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J Neural Transm (Vienna). 2012 Oct;119(10):1133-45. Epub 2012 Apr 27.

Clock gene variants in mood and anxiety disorders.

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Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, P.O. Box 30, 00271 Helsinki, Finland.


Circadian clocks are driven by signals from the habitat to match the solar day and to reset their phase relative to local time. A key function of the circadian clocks allows individuals to anticipate routine environmental conditions and to adjust their behaviors to the change of conditions. In clinical practice mood, anxiety and alcohol use disorders are often comorbid conditions. Clinical data have demonstrated that there are abnormalities in the circadian rhythms in patients with mood disorders and those with alcohol use disorders. Recent findings of molecular genetics have yielded the first insight into the targets of interest. Circadian clock gene variants are a fruitful target for elucidation of the pathogenesis. The findings that have gained support indicate that genetic variants of RORA (rs2028122) and CRY1 (rs2287161) associate with depressive disorder, those of RORB (rs7022435, rs3750420, rs1157358, rs3903529) and NR1D1 (rs2314339) with bipolar disorder, and those of NPAS2 (rs11541353) and CRY2 (rs10838524) with seasonal affective disorder or winter depression. Concerning anxiety disorders and alcohol use disorders, the current findings are preliminary and need further verification to explain the association of ARNTL2, being suggestive only, with social phobia (rs2306073) and with alcohol abuse (rs7958822, rs4964057).

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