Faculty

Zachary Z Freyberg, MD, PhD

Associate Professor of Psychiatry and Cell Biology

Contact Details

3811 O'Hara St.
Pittsburgh
 
PA
 
15213
Email
Website
CNUP faculty profile

Education & Training

MD
Albert Einstein College of Medicine
PhD
Developmental & Molecular Biology, Albert Einstein College of Medicine
Psychiatry, Payne Whitney Clinic of New York Presbyterian Hospital, Cornell University
Schizophrenia Research, Columbia University

Specialty Certifications

Board Certification
American Board of Psychiatry and Neurology

Current Appointments

Associate Director, Psychiatry Research Pathway

Professional Affiliations

Member, American College of Neuropsychopharmacology
Member, Molecular Psychiatry Association
Member, Dopamine Society

Selected Honors & Awards

Elected Member, American College of Neuropsychopharmacology
Elected Member, American Society for Clinical Investigation
A.E. Bennett Award for Basic Research, Society of Biological Psychiatry
Rising Star Research Award, Pittsburgh Foundation
Leon Levy Foundation Investigator Award, Leon Levy Foundation

Research Interests

Activity-dependent local translation in Alzheimers; Dopamine neuron vulnerability; aging & Parkinson's; Antipsychotic drug-induced metabolic syndrome
Selected Research Publications & Products
  1. Enriquez-Traba J, Yarur-Castillo HE, Flores RJ, Weil T, Roy S, Usdin TB, LaGamma CT, Arenivar M, Wang H, Tsai VS, Moritz AE, Sibley DR, Moratalla R, Freyberg Z (Co-Corresponding Author), Tejeda HA. Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors. Nature Neuroscience 2025; 28(1):105-121. PMID: 39653808.
  2. Buck SA, Mabry SJ, Kunkhyen T, Yang Z, Rubin SA, Yang J, Cheetham CEJ, Freyberg Z. dVGLUT mediates sex differences in dopamine neuron mitochondrial function across aging and in a Parkinsons disease model. Aging Cell 2025; e70096. PMID: 40354193.
  3. Bonifazi A, Ellenberger M, Farino ZJ, Aslanoglou D, Rais R, Pereira S, Mantilla-Riva JO, Boateng CA, Eshleman AJ, Janowsky A, Hahn MK, Schwartz GJ, Slusher BS, Newman AH, Freyberg Z. Development of novel tools for dissection of central versus peripheral dopamine D2-like receptor signaling in dysglycemia. Diabetes 2024; 73(9): 1-16. PMID: 38869519.
  4. Carter SD, Hampton CM, Langlois R, Melero R, Farino ZJ, Li W, Calderon MJ, Wallace CT, Tran NH, Grassucci RA, Siegmund SE, Pemberton J, Morgenstern TJ, Aguilar JI, Greenberg NL, Levy ES, Yi E, Mitchell WG, Rice WJ, Wigge C, Pilli J, George EW, Aslanoglou D, Courel M, Freyberg RJ, Javitch JA, Area-Gomez E, Shiva S, Bartolini F, Volchuk A, Murray SA, Aridor M, Fish KN, Walter P, Balla T, Fass D, Wolf SG, Watkins SC, Carazo JM, Jensen GJ, Frank J, Freyberg Z. Ribosome-Associated Vesicles: A dynamic vesicular endoplasmic reticulum in secretory cells. Science Advances 2020; 6(14):eaay9572. PMID: 32270040.
  5. Aguilar JI, Dunn M, Mingote S, Karam CS, Farino ZJ, Sonders MS, Choi SJ, Grygoruk A, Zhang Y, Cela C, Choi BJ, Flores J, Freyberg RJ, McCabe BD, Mosharov EV, Krantz DE, Javitch JA, Sulzer D, Sames D, Rayport S, Freyberg Z. Neuronal depolarization drives increased dopamine synaptic vesicle loading via VGLUT. Neuron 2017; 95(5):1074-1088. PMID: 28823729.

Clinical Interests

Antipsychotic drug-induced metabolic disorders; Mechanisms of antipsychotic drug actions
Selected Clinical Publications & Products
  1. Smith ECC, Agarwal SM, Panganiban KJ, Maksyutynska K, Monteiro J, Lee J, Prasad F, Ji A, Shah D, Cavalier S, Prabhune RU, Radoncic E, Yang Z, Fuller K, McCarthy MJ, Prestwood TR, Ballon JS, Correll CU, Hahn MK, Freyberg Z. Antipsychotic drugs are associated with dysregulations in glucose homeostasis irrespective of medication type, dose, and treatment duration: A systematic review and meta-analysis. JAMA Psychiatry 2025 Aug. PMID: 40864439.
  2. Freyberg Z, Andreazza AC, McClung CA, Phillips ML. Linking mitochondrial dysfunction, neurotransmitter, neural network abnormalities and mania: Elucidating neurobiological mechanisms of the therapeutic effect of the ketogenic diet in Bipolar Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2024; 23:S2451-9022(24)00199-X. PMID: 39053576.
  3. Buck SA, Erickson-Oberg QM, Logan RW, Freyberg Z. Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia. Molecular Psychiatry 2022; 27(9):3583-3591. PMID: 35681081.
  4. Freyberg Z, Gittes GK. Roles of pancreatic islet catecholamine neurotransmitters in glycemic control and in antipsychotic drug-induced dysglycemia. Diabetes 2023; 72(1):3-15. PMID: 36538602.
  5. Freyberg Z, Ferrando SJ, Javitch JA. Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. Am J Psychiatry 2010 Apr; 167(4): 388-396. PMID: 19917593.

Education Interests

Medical, graduate student & resident education; Research mentorship
Selected Education Publications & Products
  1. Pillinger T, Ehrenreich H, Freyberg Z, Hahn M, Mack M, Milaneschi Y, Perry B, Upthegrove R. Serious Mental Illness as a Multisystem Metabolic Disorder: From Brain to Body and Back Again, in: ngr D and Ford JM (eds.) Metabolic Neuropsychiatry, Strngmann Forum Reports (J R Lupp, series editor). 2025; Springer-Nature, Cham, Switzerland.
  2. Freyberg R, Freyberg Z. Behavioral and Social Sciences. in: Ferrando S, (ed.), Psychiatry-In-Review 2006. Educational Testing and Assessment Systems, NY, NY.
  3. Freyberg Z, Savitz A. Schizophrenia. in Ferrando S, (ed.), Psychiatry-In-Review 2006. Educational Testing and Assessment Systems, NY, NY.
  4. Freyberg Z. Schizophrenia and Violence. in: Barnhill J, (ed.), Approaching the Psychiatric Patient 1st Edition 2008. APA Press, Washington, D.C.

Pitt Psychiatry Research Published in Molecular Psychiatry

Collage of Molecular Psychiatry Co-Authors

Multiple Pitt Psychiatry investigators have recently published studies in Molecular Psychiatry. Below is a roundup of recent original research on adolescent neurodevelopment, aging and cognition, and the association between sleep and psychosis. Adolescent maturation of dorsolateral prefrontal cortex glutamate: GABA and cognitive function is supported by dopamine-related neurobiology Pitt Psychiatry investigators...

Nature Neuroscience: Dissociable Control of Motivation and Reinforcement by Distinct Ventral Striatal Dopamine Receptors

Dr. Zachary Freyberg

Dopamine transmission is essential for reward processes including motivation and reinforcement. Motivation is the internal process activating and directing behavior, and reinforcement increases the likelihood of a behavior through stimulus–response and action–outcome associations. The nucleus accumbens medial shell within the striatum serves as a key hub for reward-related behaviors, receiving dopaminergic inputs...

Psychiatry Residents Present Robust Research at the 7th Annual Psychiatry Research Pathway Symposium

PRP Residents and Mentors

The Psychiatry Research Pathway (PRP) Symposium provides UPMC Western Psychiatric Hospital residents engaged in research the opportunity to present their work to fellow residents, faculty mentors, T32 postdoctoral research program directors, and interested members of our academic community. This year, the PRP Symposium began with a panel discussion focused on interventional psychiatry, moderated by Katherine Lyman...

Diabetes: Development of Novel Tools for Dissection of Central Versus Peripheral Dopamine D2-Like Receptor Signaling in Dysglycemia

Diabetes

Most studies examining dopaminergic modulation of metabolism have focused on D 2-like receptors (D 2, D 3, and D 4 receptors) in brain regions associated with metabolic regulation, including striatum and hypothalamus, where D 2 and D 3 receptors mediate appetite, feeding, and central glucose sensing. However, dopamine D 2-like receptors in both the central nervous system and the periphery are key modulators of...

Pitt Psychiatry Awarded $6M Baszucki Group Grant to Study the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder

Drs. Mary Phillips, Zachary Freyberg and Colleen McClung

A team of investigators led by Mary Phillips, MD, MD (Cantab) (Distinguished Professor of Psychiatry, Clinical and Translational Science, and Bioengineering, and Pittsburgh Foundation-Emmerling Endowed Chair in Psychotic Disorders), have received a Baszucki Group grant to support their new center, “Elucidating Neurobiological Mechanisms Underlying the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder (BD...