Michael J. McCarthy, M.D., Ph.D.
Assistant Adjunct Professor/Staff Psychiatrist
Bipolar Disorder Clinic (STEP)
VA San Diego Healthcare System
Mood-Sleep Clinic, MC 116A
3350 La Jolla Village Dr
San Diego, CA 9261
T: (858) 642-1520
Dr. McCarthy earned a B.S. in Biochemistry and Psychology from the University of New Mexico, before completing his doctoral training in medicine and neuroscience at Ohio State University. Dr. McCarthy developed an interest in Bipolar Disorder during his psychiatry residency at UCSD (2005-2009), and subsequently completed a post-doctoral research fellowship in the molecular biology of mood disorders and chronobiology at UCSD. Dr McCarthy joined the UCSD faculty in 2011. He is presently sees patients in the VA San Diego mood-sleep clinic, is the principle investigator on funded basic and clinical research projects in Bipolar Disorder. He is the field editor for neurobiology for Acta Psychiatrica Scandinavica, and a member of the UCSD Clinical Translation Research Institute (CTRI), and Center for Circadian Biology (CCB).
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.
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, Leckband S, and Kelsoe JR. The Pharmacogenetics of Lithium Response in Bipolar Disorder. Pharmacogenetics 2010 11: 1439-65. PMID: 21047205.
- 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 10:852-61 PMID: 21781277
- McCarthy MJ, Nievergelt CM, Kelsoe JR, Welsh DK A Survey of Genomic Studies Supports Association of the Circadian Clock with Bipolar Disorder Spectrum Illnesses and Lithium Responsive Genes. PLoS One. 2012 7(2):e32091. PMID: 22384149
- McCarthy MJ, and Welsh DK, Cellular circadian clocks in mood disorders. Journal of Biological Rhythms 2012 27: 339-352. PMID: 23010657.
- McCarthy MJ, Fernandes M, Kranzler HR, Covault JM, Welsh DK Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders. Alcoholism: Clinical and Experimental Research 2013 37:1304-10 PMID: 23550834
- McCarthy MJ, Wei H, Marnoy Z , Darvish R , McPhie D, Cohen B, and Welsh DK. Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Translational Psychiatry 2013, 3: e318. PMID: 24150227