Circadian gene alterations in the human hippocampus in major depressive disorder

Turner CA, Bunney WE, Schatzberg AF, Barchas JD, Myers RM, Jones EG, Akil H, Watson SJ
Society for Neuroscience. 2011.


Single nucleotide polymorphisms in circadian genes have been associated with mood disorders. For example, VIP and CLOCK were found to be associated with Bipolar Disorder, whereas CRY1 and NPAS2 were associated with Major Depressive Disorder (MDD). We used mRNA in situ hybridization to assess gene expression patterns of five circadian genes (CLOCK, VIP, VIPR1, NPAS2 and ADCYAP1). We analyzed the post-mortem human hippocampus of 13 controls (12 males, 1 female) and 19 individuals with MDD (12 males and 7 females). General expression patterns were as follows from high to low: CLOCK (DG, CA3, CA2, CA1), ADCYAP1 (DG, CA3=CA2, CA1), NPAS2 (DG, CA2, CA3, CA1) and VIPR1 (DG only). When collapsed across levels of the dentate gyrus of the hippocampus, VIPR1 was increased in MDD compared to controls. We are, currently, analyzing VIP gene expression by mRNA in situ hybridization. There was also a nonsignificant trend for CLOCK to be increased in the dentate gyrus in MDD compared to controls. NPAS2 and ADCYAP1 were not significantly different between the groups. Since there was only one control female, we could not statistically analyze for a gender effect in controls. We could, however, assess gender differences within MDD. There was a nonsignificant trend for a gender effect within MDD for CLOCK, with depressed males exhibiting less CLOCK expression than depressed females. There were no gender differences in MDD for VIPR1. In summary, we found altered gene expression in VIPR1 in the hippocampus of individuals with MDD. Therefore, drugs that target the VIP system may be effective antidepressants.