Major psychiatric disorders are complex diseases involving the interaction of heritable genetic variation and variable environmental factors. I am interested in how this interplay between genetics and environmental factors, i.e. environmental stressors or medical illness, leads to psychiatric illness.
Genetic variants (polymorphisms) of the serotonin transporter have been shown to influence the risk for depression. In two ongoing studies, performed in collaboration with the UW School of Nursing, we are investigating how these genetic variants affect the risk for depression in medically ill subjects. We have found that patients with irritable bowel syndrome, a painful gastrointestinal disorder, are at higher risk for co-morbid depression if they carry certain variants of the serotonin transporter gene. We are now investigating whether these same transporter gene polymorphisms also raise the risk for depression in stroke patients.
P-glycoprotein is a transport protein that eliminates beta-amyloid from the cerebrospinal fluid. Beta-amyloid is accumulated in the brain of patients with Alzheimer’s disease. We are currently investigating whether genetic polymorphisms that affect the level of P-glycoprotein production in the brain influence the risk for late-onset Alzheimer’s disease.
In another set of studies, we are investigating how the utilization of genetic information, i.e. gene expression, is different in the brain of subjects with mental illness compared to healthy controls. Our studies in animal models of depression have shown that resilience to environmental stress occurs in the presence of a characteristic pattern of large-scale gene expression changes in the hippocampus. Pending studies will expand this investigation to postmortem human brain tissue.