Psychiatric disorders

This image shows human neurons (in blue), with the C4 protein (in green) deposited on synapses.
Credit: Heather de Rivera/McCarroll Lab
Broad scientists discovered that mutations in the C4 gene are key drivers in schizophrenia by affecting synaptic pruning. This is the first time a biological mechanism behind the disease has been described. This image shows human neurons (in blue), with the C4 protein (in green) deposited on synapses. The C4 protein tags synapses for pruning by the microglia, the brain’s immune cells; Broad scientists have demonstrated an overactive version of C4 could result in excessive pruning.

The Stanley Center’s primary scientific focus is on the severe psychiatric disorders schizophrenia, bipolar disorder, and autism, and the frequently comorbid neurodevelopmental disorder, attention deficit hyperactivity disorder (ADHD). These illnesses have dire consequences for individuals, families, and societies. Fortunately, they have begun to be scientifically tractable because new genomic and computational tools have made it possible to exploit their high heritabilities. We study these disorders because they exhibit significant sharing of genetic risk variants and because their pathogenesis occurs against the shared backdrop of brain development. In addition, at this early stage, the scientific approaches to gene identification and to mechanistic follow-on studies utilize identical and often scalable methodologies.