The pathophysiology of schizophrenia and bipolar disorder is poorly understood. Until very recently, research on these disorders has mainly focused on brain circuits and cell abnormalities. An important brain component, the extracellular matrix, has been largely neglected. This is a molecular network that fills the extracellular space and surrounds all cells in the brain. The brain extracellular matrix has been shown to play a key role in brain development and in regulating adult brain plasticity.

The Berretta lab is investigating the role of extracellular matrix abnormalities in the brain in schizophrenia and bipolar disorder using translational approaches. One hypothesis we are testing is the idea that molecular pathways regulating chondroitin sulfate proteoglycans (CSPGs)–one of the main components of the extracellular matrix–may be altered in these disorders. We are doing this using a combination of in vitro studies and postmortem human tissue studies focused on the medial temporal lobe, thalamus, olfactory system and orbitofrontal cortex.

A critical component of our work is examining the correlation between any abnormalities we find in our in vitro or postmortem studies and the clinical symptoms of psychotic disorders–essentially, trying to better understand the link between pathological changes and clinical symptoms in these brain disorders.