MIT Links Rare Gene Mutation to Schizophrenia's Cognitive Struggles

MIT neuroscientists have discovered a gene mutation linked to schizophrenia. The mutation, called grin2a, disrupts a brain circuit that helps update beliefs with new information. This finding sheds light on why some patients struggle to adapt their understanding of the world. The mutation was first spotted in a large study of schizophrenia patients. It most strongly affects the mediodorsal thalamus, a brain region connected to the prefrontal cortex. Together, these areas form a circuit that manages executive control and decision-making.

Neurons in the mediodorsal thalamus normally track changes in the value of rewards. But in mice with the grin2a mutation, neural activity changed abnormally depending on their state—whether they were exploring or had already chosen an action. Using optogenetics, researchers activated these neurons and reversed the behavioural symptoms in the mice. The study was supported by organisations such as the National Institutes of Mental Health. Targeting this thalamocortical circuit may offer a way to address cognitive impairments in schizophrenia. The findings open a potential path for developing new treatments.