Burton (Burt) Angrist, a Member Emeritus who was accepted into ACNP membership in 1975, best known in the field for his early contributions to the dopamine hypothesis of schizophrenia, died May 17, 2024. He leaves behind his wife Anka, his daughter Laurel, and a global retinue of mentees, colleagues, and admirers who deeply loved this energetic, gifted, generous, humble, and most unusual character.

Burt grew up in Queens. His father, Alfred Angrist, was a prominent neuropathologist: Saturdays often found Burt playing in the morgue. College years were at Colby, medical school at Albert Einstein, and psychiatry residency at Long Island Jewish-Hillside, where an encounter with Don Klein and with his father’s friend Jerry Jaffe led Burt to dive full-tilt into researching the brain. And what a time and place to do this! Sam Gershon, recently moved to New York University (NYU) and Bellevue to build a psychopharmacology research unit, had offered Burt a postdoctoral fellowship (mentorship also from Arnold Friedhoff to a lesser extent).

Early in the fellowship, John Rotrosen, then an NYU medical student, collared him to explore whether they could collaborate using behavioral- and biochemical-pharmacology approaches to unravel pre-clinical models of dopamine function, and relate these to psychoses and movement disorders, models mostly in development at several Scandinavian labs. A quick conversation with Sam led to a fourth-year elective, a research residency, and thence to deeply cherished life-long friendships and research partnerships.

Burt advanced through the academic ranks of the NYU Department of Psychiatry to a full professorship with tenure (1980). Most of his clinical work, clinical research, and teaching was at Bellevue (1969-1980) and at the next-door VA New York Harbor Healthcare System (1980 to retirement in 1998). Much of Burt’s early work consisted of meticulous descriptions of transient stimulant-induced psychoses, often in late-night jazz musicians (and others) brought shackled by police to the old Bellevue emergency room and misdiagnosed with acute schizophrenia until they cleared in a day or two. From this beginning and with the help of enthusiastic mentees and local and international collaborators, Burt’s work evolved in a beautifully linear way from the purely observational, to highly sophisticated hypotheses-driven experiments. Over the years, Burt mentored and inspired numerous junior investigators including Adam Wolkin, Michael Sanfilipo, Erica Duncan, and Len Adler. He collaborated with other investigators around the world. He particularly treasured his participation in the ACNP where he remained a Fellow for the latter years of his life.

Burt’s descriptions of stimulant psychoses in humans led to translational work on schizophrenia in the context of the then emerging dopamine hypothesis using behavioral- and biochemical-pharmacology approaches in animals, and related approaches in humans (psychiatric symptomatology [positive and negative symptoms], neurological effects [akathisia, tardive dyskinesia, extrapyramidal symptoms], and neuroendocrine measures). Some of this work used agonists and antagonists as tools to probe dopamine function in schizophrenia. Related work included clinical trials with virtually all of the “atypical” antipsychotic agents and extensive studies on the prevalence and treatment of neuroleptic-induced akathisia and tardive dyskinesia. Together, this early work (with John Rotrosen, Eitan Friedman, Edward Sachar, Michael Stanley, Steve Matthysse, Lenard Adler, and others) helped consolidate and buttress our understanding of dopamine’s role in mediating psychiatric symptoms and treatment-related movement disorders. This research served as a foundation for dozens of new hypotheses, hundreds of grants, the development of dozens of antipsychotic “me-too” agents, and to our present understanding of mechanisms of action antipsychotics.

In the late 1970s, Sam, Burt, and John met with Tibor Farkas, an immensely colorful Hungarian psychiatrist who gave a pitch on how great it would be to image brain glucose metabolism, neurotransmitter levels, and receptor ligands in vivo by way of the newly emerging PET technology. From this conversation a collaboration was born with Alfred Wolf, a renowned fluorine chemist and chair of the chemistry department at Brookhaven National Laboratory, Adam Wolkin, a budding schizophrenia/imaging researcher at the VA, Jonathan Brodie at NYU/Bellevue, Joanna Fowler at Brookhaven National Laboratory, and Nora Volkow, who joined straight out of medical school. In the early 1980s the group began using 18F-DG to probe brain metabolism in schizophrenia patients. Key findings included: (a) frontal hypo-metabolism and relative subcortical hyper-metabolism associated with chronic schizophrenia, findings that have been widely replicated; (b) amphetamine reduced-, and haloperidol increased- metabolism; (c) schizophrenia negative symptoms highly correlated with frontal hypo-metabolism; and (d) haloperidol plasma levels and brain receptor occupancy relationships clearly defined and shown not to differ between treatment-responsive and treatment-nonresponsive schizophrenia. This work contributed hugely to the rapidly growing field of molecular neuroimaging and advances in knowledge of schizophrenia pathophysiology.

The core theme running through Burt’s life’s work wraps together stimulants, dopamine, psychosis, treatment, and neural circuits mediating and modulating symptoms of schizophrenia and stimulant abuse. Like most big advances in neuroscience, the data didn’t always agree due to differences in design or implementation that needed to be resolved. Burt approached these disagreements with rigor but also with respect and gleeful energy. The first time Burt and Sam took John to a scientific meeting Burt confessed, “When we were kids preparing for a street brawl, we’d dress in our most ragged clothes and hide between parked cars; now we dress in our best, sometimes with a necktie, and talk behind lecterns.” He was a consummately skilled clinician. Countless times even the most disorganized of our VA schizophrenia patients responded positively to his empathic, patient, and meticulous interviewing style. Throughout his illustrious career, he maintained a rather iconoclastic attitude to administrative burdens that took his time away from doing science.

Burt loved ACNP with a passion surely known by a handful of founding and early members but remarkable nonetheless. He attended all but a very few meetings from his acceptance to his death, and prepared assiduously beforehand for his own presentations, planned all the talks he would attend, whom to run with, swim or snorkel with, eat with, and drink with. For each of his many official and unofficial mentees he laid out personalized plans for the entire meeting with introductions to be made, symposia to attend, meetings to sit in on. Burt loved being amongst ACNP attendees, approaching them with his characteristic humility and respect. And he took great pride in organizing informal meetings at the bar to explore and resolve differences in the theory or practice of our science.

Burt’s deep love of the outdoors and of partaking in intense physical activity in nature began in college and lasted his lifetime. This was the “other” part of Burt that many in ACNP didn’t really know, a part that he took on with the same intensity, truth-seeking, and tenacity he brought to his science. In his youth Burt joined up with a merry band of prankster rock-climbers who established the Vulgarian Rock Climbing Society based in the Shawangunk Mountains (“Gunks” an hour north of New York City), and published the Vulgarian Digest, one of its earliest editions sporting a picture of an unclad Vulgarian a hundred feet above the base of a spectacular rock face. Burt played no small part in shaping the Vulgarians, defining rivals (often from the Ivy League climbing clubs) who brought manners, rules, and dress-codes to the Gunks but couldn’t hold a candle to the Vulgarians’ climbing prowess. His love of the Gunks lasted decades, including hiking, skiing, swimming, canoeing, and in later years living at his beloved cabin with Anka.

Burt’s personality was outsized. He was hilarious, saucy, joyful, humble, and deeply caring of family, friends, and colleagues. Talks with him about science were insightful and passionate but also gleeful and peppered with ribald jokes. His deep friendships, genuine interest in each of us as individuals and budding scientists, his curiosity, humor, and creativity that spilled over to scrawling study designs on the backs of barroom napkins, his devotion to his mentees, and his everlasting loyalty were evident from the beginning, and became legendary as Burt aged into one of Grand Old Men who make membership in ACNP and the Vulgarians so special. ACNP and the world is less bright without him.

For more on Burt we encourage you to view his ACNP legacy project interview by Dr. David Janowsky, upon the 50th Anniversary of the ACNP (at v.plnk.co/ACNP/50th/Interviews/BURTON_ANGRIST.m4v).