Over the past 20 years, Dr. Kelsoe has been focused on using a variety of molecular genetic methods to identify the specific genes that predispose to bipolar disorder. He has used positional cloning methods such as linkage and association in families in which the illness is genetically transmitted and has employed animal models of bipolar disorder to identify possible candidate genes. This approach has led to the identification of the gene for G protein receptor kinase 3 (GRK3) as a likely gene for bipolar disorder on chromosome 22. Dr. Kelsoe directs the Bipolar Genome Study (BiGS), a 13-site consortium focused on identifying genes for bipolar disorders, and co-directs the Psychiatric GWAS Consortium for Bipolar Disorder (PGC-BD), an international collaborative effort designed to identify genes for bipolar disorder in a sample of over 10,000 patients.

Dr. Kelsoe is also the Medical Director of the NIMH clinical research center Special Treatment and Evaluation Program (STEP) at the San Diego VA Medical Center where he specializes in the clinical treatment of chronic and refractory mood disorders.