CLOCK gene variants associated with the discrepancy between subjective and objective severity in bipolar depression

Background The discrepancy between subjective and objective severity of depressive syndromes has been proposed as a predictor of treatment outcome and suicidal risk in depression, and is associated with depressive cognitive distortions. A recent study reported that evening-type depressed patients showed higher depressive cognitions than morning-type patients. Therefore, it can be hypothesized that genetic factors affecting evening preference, such as carrying of the CLOCK rs1801260*C allele, may influence the discrepancy. Method We tested this hypothesis in 132 patients affected by a major depressive episode in the course of bipolar disorder. The severity of depression was evaluated using self-rated (Beck Depression Inventory: BDI) and observer-rated (Hamilton Depression Rating Scale: HDRS) measures. The BDI-HDRS discrepancy score was calculated and the effects of the rs1801260 polymorphism on this score and on depressive cognitive distortions, as measured on the Cognitions Questionnaire, were examined. Results The rs1801260*C carriers showed higher BDI-HDRS discrepancy scores than T/T homozygotes. Mediation analysis using bootstrapping procedures revealed that the dimension of depressive cognition “hopelessness” fully mediates the association between the rs1801260 polymorphism and the BDI-HDRS discrepancy. Limitations Many gene polymorphisms other than CLOCK rs1801260 may also influence the BDI-HDRS discrepancy and depressive cognitive distortions. Conclusion Our current results suggest that factors affecting the biological clock can influence the “non-clock” psychopathological features of mood disorders.