Michael J. McCarthy MD, PhD
Assistant Adjunct Professor/Staff Psychiatrist VASDHS Bipolar Disorder Clinic (STEP)
Biography: Dr McCarthy graduated from the University of New Mexico with undergraduate majors in Biochemistry and Psychology in 1996. In 2005, he completed his doctoral medical and research training in neuropharmacology at Ohio State University. He did his residency in Psychiatry at UCSD, completing the research track and serving as the chief resident for research in 2009. From 2009-2011 he completed a research fellowship in Psychiatric Genetics and Chronobiology under the mentorship of David Welsh and John Kelsoe. Dr McCarthy joined the UCSD faculty in 2011 and presently sees patients in the VASDHS clinic for bipolar disorder, conducts research in clinical pharmacogenetics, and does basic molecular biology, examining circadian clock function in cells from patients with psychiatric illness such as bipolar disorder and alcoholism.
Research Focus: Due to regular intervals of light and dark caused by the Earth’s rotation around the sun, circadian clock genes have been selected through evolution to assist living organisms (including humans) in dealing with changes in temperature, food availability and social interaction. These genes have been shown to govern not only sleep wake behaviors, but also the brain’s reward and motivation systems. For these reasons, clock genes have been implicated in mood disorders such as bipolar disorder and major depression, and also substances abuse disorders like alcoholism. Clinically, the potential for clock gene influence is reinforced by features of these illnesses in which the commonly encountered alterations in sleep wake cycles, appetite, and other rhythmic behaviors are responsive to light availability and/or season. Similarly, lithium, a medication for treating mood disorders, has effects on rhythmic daily behaviors and affects the expression of several clock genes.
In the laboratory, we are using cell lines and DNA from psychiatric patients to examine circadian clock genes. We measure clock gene expression using bioluminescent reporter assays to determine if their rhythms are disturbed relative to cells from unaffected subjects, or if the expression rhythms respond differentially to conditions like lithium treatment or stress. We also examine genetic variants in candidate clock genes to determine if these are associated with clinical features of mood disorders such as lithium response. Where possible, we link associated genetic variants to functional differences in gene regulation.
Clinical Focus: I treat veterans suffering from disturbances in mood where bipolar disorder is considered as likely in the differential diagnosis. Therefore, many of my patients have bipolar disorder, but others may be diagnosed with major depression, personality disorders or psychotic disorders like schizophrenia. Many patients have multiple diagnoses, including post-traumatic stress disorder and substance use disorders. In some cases, I use pharmacogenetic tools or collect genetic samples in hopes of establishing biological predictors of medication response in the future.
McCarthy MJ, Nievergelt CM, Shekhtman T, Kripke DF, Welsh DK, and Kelsoe JR. Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder. Genes, Brain Behavior 2011 (in press).
McCarthy MJ, Zhang H, Neff NH, and Hadjiconstantinou M. Desensitization of delta opioid receptors in the nucleus accumbens during nicotine withdrawal. Psychopharmacology 2011 213:735-44. PMID:20941594.
McCarthy MJ, Leckband S, and Kelsoe JR. The Pharmacogenetics of Lithium Response in Bipolar Disorder. Pharmacogenetics 2010 11: 1439-65. PMID:21047205.
McCarthy MJ, Nissen S, Barrett TB, Kelsoe JR, and Turner EE. Allele specific analysis of the ADRBK2 gene in lymphoblastoid cells from bipolar disorder patients. J Psychiatr Research 2010 44: 201-8. PMID: 19766236.
McCarthy MJ, Zhang H, Neff NH, and Hadjiconstantinou M. Nicotine withdrawal and kappa opioid receptors. Psychopharmacology (Berl). 2010 210: 221-9. PMID: 19806344