McLean Hospital 115 Mill Street Belmont, MA 02478
Frank I. Tarazi, MBBS, PhD, MBA, is an associate professor of psychiatry at Harvard Medical School and director of the Psychiatric Neuroscience Laboratory at McLean Hospital. His research focuses on better understanding the pathophysiology of neuropsychiatric disorders and their improved treatment. He has been awarded research funding from NARSAD, NIH, the Stanley Foundation, and from several pharmaceutical and biotechnology companies. Dr. Tarazi is an associate editor of CNS Spectrums and Pharmacology & Therapeutics and serves on the editorial boards of several other journals.
Dr. Tarazi has numerous publications including a chapter in Goodman and Gilman’s The Pharmacological Basis of Therapeutics. He has received several honors and awards from leading societies and institutions and is a fellow of the American College of Neurpsychopharmacology (ACNP). Dr. Tarazi is a member of the World Economic Forum’s Global Agenda Council on Brain Research.
Dr. Tarazi’s Psychiatric Neuroscience Laboratory, which was established in 2004, has a long-standing interest in understanding the pathology and neurobiology of psychiatric disorders including Alzheimer’s disease, schizophrenia, depression, and ADHD. The lab focuses on clarifying the mechanisms of brain plasticity, gene expression, and responses of cellular elements to different psychotropic drugs, and have identified several novel brain sites and pathways that constitute attractive targets for new drug development. Dr. Tarazi and his group have also established several animal models that provide close presentations of the core symptoms of neuropsychiatric conditions, and have efficiently utilized these models for assessing the actions of standard and experimental medications.
Dr. Tarazi studies the behavioral, genetic, molecular, and cellular mechanisms that mediate the actions of dissimilar psychotropic drugs by using animal models that mimic the core symptoms of different neuropsychiatric diseases. He also uses advanced genetic, molecular, and cellular techniques that are integral components of drug discovery processes.
The mission of the laboratory is to continue discovering additional translational principles that provide new insights into the neurobiology of neuropsychiatric disorders, as well as developing much-needed novel drugs that are effective in managing these diseases, with superior safety, tolerability, and long-term maintenance. Several of the compounds tested in the lab have been FDA-approved including aripiprazole (Abilify®), brexpiprazole (Rexulti®), iloperidone (Fanapt®), asenapine (Saphris®), vilazodone (Viibryd®), atomoxetine (Strattera®), and cariprazine (Vraylar®).
In order to clarify the basis of limited responses in children and adolescents to standard adult antidepressant treatment of adult major depressive disorder, Dr. Tarazi and his staff analyzed gene expression in developing animals after treatment with several antidepressant drugs using microarray gene chips. They found that antidepressant drugs interfere with the expression of genes involved in cell signaling, survival, and protein metabolism. In addition, these agents specifically regulate the induction of a highly specific transcriptional program in brain cells, which may contribute to the limited clinical efficacy of antidepressant drugs in pediatric patients.
Binge eating disorder (BED) presents as the compulsive, excessive consumption of highly palatable foods. The lab recently developed an animal model of BED in which rats are given irregular, limited access to chocolate along with normal chow. Over a period of 4 weeks, rats develop robust, binge eating (BE) of the chocolate with concomitant reduction in their intake of normal chow and also showed increased impulsive behaviors. They found the expression of GABA biomarkers (GAD65 and GAD67 mRNA) and dopamine receptors are reduced in select brain regions of BE rats. The findings suggest that alterations in GABA and DA neurotransmission in the forebrain regions may contribute to the impulsive behaviors observed in BED patients.
Dr. Tarazi’s group established an animal model that provides face, construct, and predictive validities for ADHD. Using this model, they screen for the behavioral activity of standard and novel treatments for ADHD. They have reported that the triple reuptake inhibitor centanafadine was effective in this model, which supports the clinical development of centanafadine as a novel and improved treatment for ADHD.
Tayeb HO, Murray ED, Price BH, Tarazi FI. Bapineuzumab and solanezumab for Alzheimer’s disease: is the ‘amyloid cascade hypothesis’ still alive? Expert Opinion on Biological Therapy 2013;13(7):1075-1084.
Tsapakis EM, Fernandes C, Moran-Gates T, Basu A, Sugden K, Aitchison KJ, Tarazi FI. Effects of antidepressant drug exposure on gene expression in the developing cerebral cortex. Synapse 2014;68(5):209-220.
Hutson PH, Tarazi FI, Madhoo M, Slawecki C, Patkar AA. Preclinical pharmacology of amphetamine: implications for the treatment of neuropsychiatric disorders. Pharmacology & Therapeutics 2014;143(3):253-264.
Tarazi FI, Schetz JA, eds. Neurological and Psychiatric Disorders: From Bench to Bedside. Totowa, NJ: Humana Press, 2005.
Belmont campus – Mailman Research Center, Room 306