Steven P. Hamilton, M.D., Ph.D.
Assistant Professor of Psychiatry



Contact Information:
SteveH@lppi.ucsf.edu
Tel: (415) 476-7889
Fax: (415) 476-7800
Box NGL, LPPI LP68

Links:
Canine Behavioral Genetics
Publications

Pharmacogenomics of Antidepressant Response

The primary area of interest in the laboratory is the genetics of psychiatric disorders. It is clear that there is a genetic component to the susceptibility to most major psychiatric disorders, like anxiety and mood disorders. But as with complex genetic disorders like diabetes and hypertension, identifying genes for psychiatric conditions has proven difficult. Advances in molecular genetics promise to make the mapping of genes for mood and anxiety disorder more efficient and productive. We are using such techniques in the laboratory as tools for isolating genes for anxiety disorders and for determining which genes are involved with a clinical response to antidepressant medication.

The two principle projects in the lab are:
1. Pharmacogenomics of antidepressant response: Since many antidepressants target the products of known genes, the techniques of pharmacogenomics, or the genome-wide analysis of the heritable variation to drug response, is of substantial clinical interest. This project harnesses molecular genetics techniques for the large-scale discovery of DNA variations in candidate genes for depression relevant to pharmacotherapy in a population of depressives treated with fluoxetine (Prozac). One set of candidate genes are those for which pharmacodynamic considerations make them candidates for involvement with antidepressant response. These include the serotonin and norepinephrine transporters, three serotonin receptors, and neuropeptide-related genes. The second class will be genes for which pharmacokinetic considerations implicate them in medication response, such as hepatic enzymes like CYP2D6. We are currently determining if such variants are associated with medication response. This work may have the ramification that genetic differentiation of depressives who are responders to specific medication from non-responders may be a tool for developing a rational, genetically-informed psychopharmacology.

2. Genetic analysis of human and canine panic disorder: Panic disorder is a common anxiety disorder with a moderate genetic component. It is characterized by panic attacks, accompanied by severe anxiety about having further panic attacks. In collaboration with colleagues at several institutions, we are involved in efforts to map genes for panic disorder in multiples human pedigrees as well as in canine pedigrees that exhibit an anxiety syndrome highly similar to human panic disorder. We are using standard genetic linkage and association strategies, and in addition will be pursuing linkage disequilibrium mapping approaches using high-density SNP markers. A complementary candidate gene approach is also being used to identify genes involved in human and canine panic disorder.