Rochester, Minnesota


MFrye@mayo.edu Clinical Profile


Mark A. Frye, M.D., has a research focus on genomics, brain imaging, and neuroendocrinology of mood disorders and alcoholism, complementing his clinical interests in bipolar disorder, depression and alcoholism.

Dr. Frye receives research support from the National Institute of Mental Health, Mayo Clinic's Samuel C. Johnson Genomics of Addiction Program, SC Johnson Giving, Inc., the Marriott family and the Mayo Clinic Center for Individualized Medicine. He has also received funding from the National Institute on Alcohol Abuse and Alcoholism.

Focus areas

  • Neurobiology of bipolar disorders. Dr. Frye and his team have established the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder in an attempt to identify and understand the underpinning mechanisms of bipolar disorders. They are utilizing cutting-edge technologies in DNA genomics, mtDNA genomics, proteomics and epigenomics.

    Since bipolar disorders are a heterogenous group of disorders, Dr. Frye and his team are focusing their studies on homogenous subgroups of bipolar disorders through comprehensive, meticulous phenotyping.

  • Magnetic resonance spectroscopy (MRS) in psychiatric disorders. Dr. Frye is developing an MRS library by combining several different MRS studies conducted by investigators in Mayo Clinic's Department of Psychiatry and Psychology. This library will allow researchers to access a large-polled sample of MRS data when conducting research on brain regions and metabolites of interest.
  • Psychopharmacology of bipolar disorders. Dr. Frye is interested in identifying genetic biomarkers for antidepressant-induced mania.
  • Bipolar disorder and alcoholism comorbidity. Dr. Frye has an interest in looking at metabolite changes in the brains of patients with alcohol disorders before and after treatment with acamprosate, as compared with those who did not take acamprosate.
  • Acceleration and augmentation strategies in depression. Dr. Frye is looking at genetic differences between those who do and do not respond well to lamotrigine or fluoxetine for treatment of bipolar depression. He is assessing how genetic differences may influence the side effects patients experience while on either lamotrigine or fluoxetine.

Significance to patient care

Dr. Frye seeks to uncover the underpinning mechanisms of bipolar disorder through genomic studies using the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder and neuroimaging studies using the Mayo Clinic MRS library. Through the discovery of proteomic biomarkers in these studies, he is creating a validated test for a reliable bipolar disorder diagnosis.

The current understanding of the underpinning mechanisms of bipolar disorder is poor, and unlike other medical disorders, the diagnosis of bipolar disorder is still based on behavioral observation and symptom endorsement without corresponding biological validation.

Dr. Frye aims to address the unmet clinical needs of bipolar patients by optimizing medical treatment of bipolar depression through basic science research and translational clinical trials.

Professional highlights

  • Scientific reviewer, Interventions Committee for Adult Disorders (ITVA), National Institute of Mental Health, 2013-present
  • Editorial board, International Journal of Bipolar Disorders, 2013-present
  • Editorial board, World Journal of Psychiatry, 2011-present
  • Stephen and Shelley Jackson Family Professor of Individualized Medicine, 2017
  • Director, Bipolar Disorder Research Program, University of California, Los Angeles, 1998-2006


Primary Appointment

  1. Consultant, Department of Psychiatry & Psychology

Academic Rank

  1. Professor of Psychiatry


  1. Research Fellowship National Institute of Mental Health, Biological Psychiatry Branch
  2. Resident - General Psychiatry David Geffen School of Medicine, UCLA Neuropsychiatric Institute
  3. MD University of Minnesota School of Medicine
  4. Diplom - Diplome de Langue L'Alliance Francaise
  5. BA - Biology Luther College

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