Widespread Dopamine Deficits Found in Brains of Patients with Schizophrenia

Columbia researchers have found evidence of reduced levels of the transmitter dopamine in the frontal cortex of patients with schizophrenia. This deficit, which affects the ability of the frontal cortex to become activated when subjects are faced with cognitive demands such as memory tasks, is most likely responsible for the cognitive deficits seen in patients with schizophrenia. The study was published online today in JAMA Psychiatry.

This dopamine deficit in the frontal cortex is in contrast to the excess dopamine that researchers have found in the striatum, a region deep inside the brain. That excess produces the hallucinations, delusions, and thought disorder associated with psychosis.

Until now, it has been difficult to examine dopamine in the cortex, where the neurotransmitter is essential for cognition: remembering for brief intervals of time, reasoning, strategizing, and other related functions. Using PET imaging technology, first author Mark Slifstein, PhD, and colleagues compared dopamine activity in the frontal cortex in patients with schizophrenia and in healthy controls. They found that patients with schizophrenia have lower levels of dopamine in the frontal cortex.

“We also found that in patients with schizophrenia, most of the brain regions that we could image with this imaging tool have deficits in dopamine,” says Dr. Slifstein, associate professor of neurobiology (in psychiatry) at CUMC and research scientist at the New York State Psychiatric Institute.

Though researchers had suspected for a long time that the abnormal dopamine activity associated with schizophrenia was not limited to the striatum, the current study is the first to demonstrate the extent of the dysfunction.

“Recognizing the presence of cortical deficits in dopamine helps us to understand why current treatments fail to address cognitive problems and negative symptoms, which are at least partly mediated by dopamine transmission in some of these brain regions,” says principal investigator Anissa Abi-Dargham, MD, professor of psychiatry at CUMC and chief of the Division of Translational Imaging at the New York State Psychiatric Institute. “Furthermore, the information enables us to search for specific disease mechanisms and helps guide treatment developments.”