Stress and GABA in the pathogenesis of psychosis

Psychosis is the fourth leading cause of disability in the world. The first symptoms, such as hearing voices that aren't there, appear in adolescence. These symptoms result from interactions between genes and environmental risk factors like stress. Current treatments do not work for about 50 per cent of patients, and have little impact on prevention.

Psychosis is associated with producing too much of the brain chemical dopamine, but little is known about what causes this. Research in experimental animals shows that problems in regulating the response to stress lead to deficits in another brain chemical called GABA. This produces an excess of dopamine in the brain. When adolescent rats are given a drug that improves GABA function, the response to stress is reduced. This prevents an excess of dopamine.

I will use neuroimaging to study the relationship between stress, GABA and psychosis in three related studies. These studies will involve the animal model, patients with psychosis, and people at high risk of the disorder. These studies will help us to use the stress response to identify people who are most at risk of psychosis, and new ways of preventing psychosis by reducing the response to stress.