Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients

Gene polymorphisms in the mammalian biological clock system influence individual rhythms. A single nucleotide polymorphism (SNP) in the 3' flanking region of CLOCK (3111 T/C; rs1801260) influenced diurnal preference in healthy humans and caused sleep phase delay and insomnia in patients affected by bipolar disorder. Genes of the biological clock are expressed in many brain structures other than in the 'master clock' suprachiasmatic nuclei. These areas, such as cingulate cortex, are involved in the control of many human behaviors. Clock genes could then bias 'nonclock' functions such as information processing and decision making. Thirty inpatients affected by a major depressive episode underwent blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). The cognitive activation paradigm was based on a go/no-go task. Morally connoted words were presented. Genotyping of CLOCK was performed for each patients. We measured activity levels through actimetry during the day before the fMRI study. CLOCK 3111 T/C SNP was associated with activity levels in the second part of the day, neuropsychological performance and BOLD fMRI correlates (interaction of genotype and moral valence of the stimuli). Our results support the hypothesis that individual clock genotype may influence several variables linked with human behaviors in normal and psychopathological conditions.