Polymorphisms in melatonin synthesis pathways: possible influences on depression

To replicate and further explore these ideas, rs4446909 was genotyped in four research groups, as part of a panel of 610 SNPs surveyed by an Illumina Golden Gate assay. In 768 cases with delayed sleep phase disorder or matched controls, rs4446909 was indeed associated with the depressive symptoms on a self-report scale (P = 0.01, R2 = 0.007). However, there was no significant association of rs4446909 with self-reported depression in a sleep clinic patient group or with two groups of elderly men and women from multicenter studies, nor was the response to lithium treatment associated with rs4446909 in bipolar patients. No associations of two AANAT SNPs with depression were found.The evidence did not support a strong influence of rs4446909 upon mood, but the partial replication may be consistent with a modest effect. It is possible that larger or younger subject groups with improved phenotype ascertainment might demonstrate more persuasive replication.The psychiatric literature contains a number of inconsistent studies of melatonin in affective disorders, reporting that there is a "low melatonin syndrome" or high morning melatonin associated with depression, or that the timing of melatonin secretion may be either advanced or delayed [1-7]. The circadian phase of melatonin secretion has been hypothesized to be a causal element in affective disorders. New evidence suggests that late melatonin elevations may suppress pars tuberalis TEF, a photoperiodic switch which might control human depression [8]. Such a mechanism would be consistent with apparent comorbidity of delayed sleep phase disorder and depression [9]. The problems contributing to inconsistent theories about melatonin's role in depression include the difficulties of obtaining complete overnight melatonin secretion profiles from onset to offset, especially in very disturbed patients, assay difficulties, differences between the home and hospital environments, effects of medications, and the heterogeneity of patie