Evidence for a Role of Neuropeptide Y Receptor Variant in Depression

Genetic variation can increase the predisposition to major depressive disorder.
Genetic variation can increase the predisposition to major depressive disorder.

It is known that environmental stressors have a major influence upon mood, and that the susceptibility to depression is influenced by stressful experiences. Neuropeptide Y (NPY), for example, has previously been reported to play a role in stress-related disorders, such as depression.

With regard to the contribution of NPY in depression, newly published data indicate that there is a significant interaction between major depressive disorder (MDD) and a functional variant in the neuropeptide Y receptor Y2 (NPY2R) promoter. These findings were published in Psychiatry Genetics.

Genetic variation in NPY2R was previously hypothesized to have an influence in determining the individual's response to environmental stress. For example, the NPY2R variant rs6857715 has previously been implicated in alcohol dependence and obesity. It is also known that stress increases the risk for both of these conditions.

In the current study, investigators performed a genetic analysis to determine the association between the C-allele of the NPY2R promoter variant rs6857715 and MDD. They genotyped 595 patients diagnosed with major depression, and compared the results with those of 1 295 typical, healthy control participants.

Results indicate a significant association between MDD and the C-allele of rs6857715 (P=0.02, OR=1.18).  In the second step of the analysis, investigators included only the participants without a comorbid condition, including alcohol dependence/abuse and increased weight/obesity.

Again, the association between MDD and the C-allele of rs6857715 was found to be significant when the data from controls were compared with those from patients without alcohol dependence (P=0.038, OR=1.18), without increased weight (P=0.006, OR=1.23), and without comorbid alcohol dependence and increased weight (P=0.008, OR=1.25).

“Exclusion of subgroups showed that this association is genuinely attributable to MDD and not to comorbid alcohol dependence/alcohol abuse or increased weight/appetite,” investigators concluded.

Reference

Treutlein J, Strohmair J, Frank J, et al. Association between neuropeptide T receptor Y2 promoter variant rs6857715 and major depressive disorder. Psychiatr Genet. 2016. [Epub ahead of print]

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