A specific allele for corticotrophin-releasing hormone is associated with a considerably better response to antidepressant therapy in an American ethnic group, providing the first direct evidence that genotype can predict response to antidepressants, according to an article in the December issue of Molecular Psychiatry.

Researchers in recent years have been trying to identify genetic factors predictive of response to antidepressants. Previous studies have found evidence for the role of corticotrophin-releasing hormone in depression. Based on previous findings, researchers have most closely focused on drugs that target serotonin transports, such as fluoxetine. None of the previous studies had focused on genes responsible for response to stressors, such as the gene for corticotrophin-releasing hormone.

In the current research, investigators genotyped 80 Mexican-American adults who were participating in an 8-week, randomized, double-blind trial of fluoxetine versus desipramine. They found that depressed and highly anxious patients homozygous for the CRH1 gene variant (allele) had a 70-percent greater reduction in anxiety and a 30-percent greater reduction in depression in response to either anti-depressant than did patients without a copy of the variant.

Although the findings need to be confirmed in larger and different patient populations, the authors believe the results represent important support for the hypothesis that response to antidepressant therapy may be genetically heterogeneous and that other genes involved in the stress-inflammatory response pathways may play a role in depression and antidepressant response.