BRIAN J. MICKEY
Associate Professor of Psychiatry
Brain and Behavior
Neurobiology of Disease
Neuroscience of mood disorders
Brian Mickey studied physics and biology at the University of Washington, Seattle, and then earned his MD and PhD in Neuroscience at the University of Michigan, Ann Arbor. After psychiatry residency and postdoctoral fellowship, he joined the faculty at the University of Michigan. In 2015, he moved to the University of Utah, where he is a faculty member in the Department of Psychiatry and in the Neuroscience Program. He has mentored or co-mentored more than a dozen research trainees, from high-school to post-doctoral level.
My research is focused on two themes, one basic and one translational.
Basic: Neural circuitry underlying mood and motivation in humans. Internal mood and motivational states are emergent neural phenomena that guide adaptive behaviors in mammals. Because disorders of mood and motivation are common in humans, the neural basis of these states is of great clinical importance. These phenomena are thought to arise from circuits within the brainstem, ventral basal ganglia, and medial prefrontal cortex. Our work has shown that the function of these circuits (1) varies substantially between individuals, (2) correlates with self-reports, and (3) is influenced by inherited genetic variants. Current work is examining how neural responses to monetary incentives are influenced by polymorphisms in the gene for neuropeptide Y (NPY) and other genes.
Translational: Treatment resistance and novel therapeutics for mood disorders. Severe mood disorders are among the most disabling and costly diseases worldwide, and many individuals do not respond to currently available treatments. A major barrier to development of better treatments is the heterogeneity of depressive illnesses, which have multiple underlying causes. Current work is aimed at (1) developing clinically useful biomarkers that distinguish the diverse forms of depression and (2) identifying the neural mechanisms of novel antidepressant interventions, including general anesthetics and brain stimulation therapies.
My research group uses a variety of techniques to address these questions in human subjects. Positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) assess brain function with neurochemical specificity. Functional magnetic resonance imaging (fMRI) characterizes neural responses during specific behaviors and perceptions, as well as patterns of brain connectivity at rest. Genetic analyses examine the genetic basis of individual differences in human brain function. These biological studies are combined with clinical trials methodology, including pharmacological and brain stimulation interventions, to define brain mechanisms that mediate change in mood and motivational states.
Gluskin, B.S., and Mickey, B.J. (2016) Genetic Variation and Dopamine D2 Receptor Availability: A Systematic Review and Meta-analysis of Human In Vivo Molecular Imaging Studies. Transl Psychiatry, in press.
Haq, A.U., Sitzmann, A.F., Goldman, M.L., Maixner, D.F., and Mickey, B.J. (2015) Response of Depression to Electroconvulsive Therapy: A Meta-Analysis of Clinical Predictors. J Clin Psychiatry, 76:1374.
Peciña, M., Bohnert, A.S.B., Sikora, M., Avery, E., Langenecker, S., Mickey, B.J., and Zubieta, J.K. (2015) Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. JAMA Psychiatry, 72(11):1087-1094.
Hsu, D.T., Sanford, B.J., Meyers, K.K., Love, T.M., Hazlett, K.E., Walker, S.J., Mickey, B.J., Koeppe, R.A., Langenecker, S.A., and Zubieta, J.K. (2015) It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Mol Psychiatry, 20(2):193-200.
Glaser, Y.G., Zubieta, J.K., Hsu, D.T., Villafuerte, S., Mickey, B.J., Trucco, E.M., Burmeister, M., Zucker, R.A., and Heitzeg, M.M. (2014) Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex. J Neurosci, 34(11):4099-4107.
Lohoff, F.W., Hodge, R., Narasimhan, S., Nall, A., Ferraro, T.N., Mickey, B.J., Heitzeg, M.M., Langenecker, S.A., Zubieta, J.K., Bogdan, R., Nikolova, Y.S., Drabant, E., Hariri, A.R., Bevilacqua, L., Goldman, D., and Doyle, G.A. (2014) Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing. Mol Psychiatry, 19(1):129-139.
Love, T.M., Enoch, M.A., Hodgkinson, C.A., Pecina, M., Mickey, B., Koeppe, R.A., Stohler, C.S., Goldman, D., and Zubieta, J.K. (2012) Oxytocin gene polymorphisms influence human dopaminergic function in a sex-dependent manner. Biol Psychiatry, 72(3):198-206.
Mickey, B.J., Sanford, B.J., Love, T.M., Shen, P.H., Hodgkinson, C.A., Stohler, C.S., Goldman, D., and Zubieta, J.K. (2012) Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans. J Neurosci, 32(27):9344-9350.
Hsu, D.T., Mickey, B.J., Langenecker, S.A., Heitzeg, M.M., Love, T.M., Wang, H., Kennedy, S.E., Pecina, M., Shafir, T., Hodgkinson, C.A., Enoch, M.A., Goldman, D., and Zubieta, J.K. (2012) Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing. J Neurosci, 32(9):3253-3260.
Mickey, B.J., Zhou, Z., Heitzeg, M.M., Heinz, E., Hodgkinson, C.A., Hsu, D.T., Langenecker, S.A., Love, T.M., Pecina, M., Shafir, T., Stohler, C.S., Goldman, D., and Zubieta, J.K. (2011) Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch Gen Psychiatry (JAMA Psychiatry), 68(2):158-166.
Mickey, B.J., Ducci, F., Hodgkinson, C.A., Langenecker, S.A., Goldman, D., and Zubieta, J.K. (2008) Monoamine oxidase A genotype predicts human serotonin 1A receptor availability in vivo. J Neurosci, 28(44):11354-11359.
Mickey, B.J., and Middlebrooks, J.C. (2003) Representation of auditory space by cortical neurons in awake cats. J Neurosci, 23(25):8649-8663.