Scientists have struggled for decades to crack the code of psychiatric disorders, but advances in understanding the biology of these conditions have not led to a successful new therapy in 70 years. The drugs that exist for diagnoses like schizophrenia, depression, and autism spectrum disorder are blunt, imprecise tools that do not address the full range of symptoms and often do not bring adequate relief.
But while psychiatric drug research has stagnated, and the pharmaceutical industry has largely abandoned its search for the next Prozac, research on the genetics of these disorders has blossomed.
Now a group of biologists, psychiatrists, and geneticists led by researchers at UC San Francisco and the Gladstone Institutes is leveraging that progress to forge a new path toward novel treatments for these conditions.
Armed with an $18-million grant awarded by the National Institutes of Health on September 5, 2018, the researchers are launching the Psychiatric Cell Map Initiative (PCMI), a collaborative effort to chart how gene mutations lead to psychiatric disorders in the hopes of identifying new drug targets that could prevent, treat, or even cure these conditions.
The PCMI was founded by the UCSF Quantitative Biosciences Institute (QBI) in collaboration with the Department of Psychiatry at UCSF. Founding faculty include QBI Director Nevan Krogan, PhD, a Gladstone senior investigator and a professor of cellular and molecular pharmacology at UCSF; Matthew State, MD, PhD, the Oberndorf Family Distinguished Professor and chair of psychiatry at UCSF; and Jeremy Willsey, PhD, an assistant professor in the Department of Psychiatry and the Institute for Neurodegenerative Diseases at UCSF.
The new initiative—outlined in a Perspective article published in Cell on July 26, 2018—involves a diverse set of collaborators from across UCSF, Gladstone, and the University of California system, including Jennifer Doudna, PhD, of UC Berkeley, UCSF, and the joint UC Berkeley–UCSF Innovative Genomics Institute, who recently opened a new laboratory at Gladstone to pursue biomedical applications of genome editing, as well as Steven Finkbeiner, MD, PhD, a Gladstone investigator and UCSF professor of pharmaceutical chemistry, and Trey Ideker, PhD, a computational biologist at UC San Diego. Collaborators from UCSF include David Agard, PhD; Martin Kampmann, PhD; Michael Keiser, PhD; Tomasz Nowakowski, PhD; Brian Shoichet, PhD; and Mark von Zastrow, MD, PhD.
PCMI will first tackle autism spectrum disorder, one of the best genetically characterized disorders. The researchers also plan to apply their method to Tourette disorder, childhood-onset epilepsy, and intellectual disability in the near future. In addition to helping them understand each disorder on its own, the scientists believe the cell maps will reveal overlapping proteins and pathways shared among the different diagnoses.