The commitment, which is the largest ever in psychiatric research, will support research by a collaborative network of researchers within the Stanley Center for Psychiatric Research at the Massachusetts-based Broad Institute, a biomedical research institution that brings together faculty from MIT, Harvard University, the Harvard-affiliated hospitals, and collaborators worldwide.
Over the coming years, the center and its researchers aim to accomplish at least four major goals:
- Complete a list of all genes that play roles in severe psychiatric disorders, including schizophrenia, bipolar disorder, autism, and others. They also plan to expand their sample collection efforts to understudied populations. As a first step, they plan to carry out comprehensive analysis of all genes that specify the protein building blocks of cells from 100,000 samples in the next two years;
- Reveal the biological pathways in which these genes act by working with new techniques that allow researchers to manipulate and measure the dynamic activity of genes in living cells, including lab-grown neurons produced by new stem-cell technologies. Their ultimate goal is to determine where, when, and how these genes act in human brain cells, and how in psychiatric patients those processes may go awry;
- Develop cellular and animal models that faithfully mimic human disorders. Broad researchers plan to create cellular models in the laboratory and animal models that more faithfully match both the genetic variation and the biochemical processes seen in human patients; and
- Develop chemicals to modulate biological pathways to serve as drug leads.
"This is a pivotal moment," said Thomas Insel, director of the US National Institute of Mental Health at the National Institutes of Health. "We are finally beginning to gain the deep knowledge about these disorders that we have sought for decades.”
In the last five years, the understanding of the biological causes of mental illnesses such as schizophrenia and bipolar disorder has accelerated, driven by advances in human genomics.
“Human genomics has begun to reveal the causes of these disorders. We still have a long way to go, but for the first time we can point to specific genes and biological processes. It’s now time to step on the gas pedal,” Stanley said.
The Broad Institute’s genomic work stretches back to April when the institute profiled and sequenced the genomes of lupus patients for Pfizer and EMD Serono.
Researchers at the institute have assembled the world’s largest collection of DNA samples in psychiatric research — currently at over 175,000 samples — including schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder (ADHD), and healthy control samples.
Analysis of 80,000 of these samples so far by Broad researchers and collaborators has linked more than 100 genomic regions to schizophrenia and begun to identify specific gene mutations and the critical underlying biological processes.
Eric Lander, founding director and president of the Broad Institute, added: “If we know the biological causes, we can begin to dispel the stigma around people battling mental illness, and rigorously pursue better treatments that will transform patients’ lives.”