Pharmacogenomics of antidepressant treatment

It is well known that drugs from various classes have a common antidepressant effect. Additionally, it is known that antidepressants exert their pharmacological effects only after chronic treatment. Based on those pharmacological features, we hypothesized that there may be downstream alterations in gene expression that underlie antidepressant effect. To test this hypothesis we treated adult rats daily with imipramine, fluoxetine, or saline for eight weeks. We used differential mRNA display, validated by reverse Northern blotting and PCR to identify genes that are induced in the hypothalamus by chronic treatment with either antidepressant but not with saline. We chose the hypothalamus because many features of depression such as alterations in food intake and body weight, temperature, and neuroendocrine dysregulation are due to hypothalamic dysfunction. We have now identified 23 hypothalamic ARTs (antidepressant-related transcripts). Most of them represent new sequences. These ARTs will serve as new candidates for neurobiological and neuropathological studies, for genetic association studies, and may also serve as novel targets for drug development.