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Genomic Keys to Depression Could Unlock Antidepressant Response

(PSYCHIATRIC TIMES) - As a three-generation study was published with new evidence that major depression can afflict families from one generation to the next, genomic research reported associated heightened risk for depression and specific treatment response with particular genotypes. The 20-year longitudinal family study found twice the rate of depression or anxiety in children whose parents and grandparents also had depression than in children without such a history (Arch Gen Psychiatry 2005;62[1]:29A-36). Two other recent publications offered examples of mechanisms for such familial vulnerability: In one, a defect in a gene that codes the enzyme tryptophan hydroxylase-2, integral to serotonin synthesis, was linked to depression risk (Neuron 2005;45[1]:11-16). In another, a variant in the corticotropin-releasing hormone (CRH) receptor 1 (CRHR1) gene predicted responsiveness to antidepressants (Mol Psychiatry 2004;9[12]:1075-1082).

Generational Risk

The longitudinal family study, conducted by Myrna M. Weissman, Ph.D., and colleagues, not only supports numerous other studies of depression risk in offspring of parents with major depression disorder, but finds the risk carried through several generations and suggests that it intensifies as more are affected (Arch Gen Psychiatry 2005;62[1]:29A-36). The researchers found 59.2% of the children of an afflicted parent and grandparent had a psychiatric disorder, most frequently anxiety, at the group's mean age of 12 years. They extrapolated from other data to consider the anxiety disorder at this age to be a precursor of depression in adolescence and young adulthood.

Weissman and colleagues reported that the effect of parental depression on the outcomes of children differs significantly with grandparent depression status. Children with a depressed grandparent and parent had an increased risk of an anxiety disorder (relative risk=5.17) and of any psychiatric disorder (relative risk=5.52), compared with children who had a depressed grandparent but nondepressed parents. The severity of parental depression in terms of impairment significantly increased the rate of a mood disorder in those grandchildren. In contrast, there was no significant effect of parental depressive disorder without grandparent depression on the diagnosis of grandchildren; although parental depression did affect overall functioning of their children.

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