William A. Carlezon

About

William A. Carlezon is a Professor of Psychiatry at McLean Hospital, with a research focus on the biological basis and treatment of psychiatric illnesses. His Behavioral Genetics Laboratory, founded in 1998, aims to understand how the environment affects behavior and brain biology, exploring factors such as stress, drugs, trauma, toxins, and illness. His work is relevant to neuropsychiatric disorders including depression, anxiety, PTSD, addiction, and autism. Dr. Carlezon’s lab employs behavioral tests in rats and mice to model key signs of psychiatric conditions, using strategies like genetic engineering to establish cause-effect relationships. His team has made significant contributions, including the first report that kappa-opioid receptor antagonists have antidepressant, anti-anxiety, and anti-stress effects, leading to advanced clinical trials for treatment-resistant depression. The lab collaborates with other scientists at McLean and the Broad Institute to develop novel kappa antagonists through high-throughput screening and medicinal chemistry.

Research topics

• Psychology
• Neuroscience
• Medicine
• Computer Science
• Biology
• Psychiatry
• Internal medicine
• Clinical psychology
• Chemistry
• Endocrinology

Selected publications

• Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

  Nature Reviews Neurology · 2022 · 432 citations

  Senior authorCorresponding
  PublisherOA PDFDOI

• Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep Architecture

  Biological Psychiatry · 2021 · 45 citations

  Senior authorCorresponding
  DOI

• SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration

  Nature Communications · 2024-03-25 · 30 citations

  articleOpen access

  High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperact…

  PublisherOA PDFDOI

• Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential

  Proceedings of the National Academy of Sciences · 2025-04-14 · 28 citations

  articleOpen access

  Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ). Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis. Here, we report the molecular design and de novo total synthesis of (+)-JRT, a structural analogue of lysergic acid diethylamide (…

  PublisherOA PDFDOI

• α2-containing γ-aminobutyric acid type A receptors promote stress resiliency in male mice

  Neuropsychopharmacology · 2021 · 16 citations

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21DA014789

  NIH · $158k · 2004

• Roles of nuleus accumbens CREB and Kappa function in depression

  NIH · $8.7M · 2021–2026

• NIH Grant R03DA030586

  NIH · $156k · 2013

Frequent coauthors

• Bruce M. Cohen

  McLean Hospital

  156 shared

• Elena H. Chartoff

  Harvard University

  123 shared

• Eric J. Nestler

  95 shared

• Edward G. Meloni

  Harvard University

  78 shared

• Kerry J. Ressler

  McLean Hospital

  77 shared

• Diego A. Pizzagalli

  Harvard University

  74 shared

• Rachael L. Neve

  Massachusetts General Hospital

  68 shared

• Galen Missig

  McLean Hospital

  65 shared

Labs

• William A. Carlezon LabPI

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