Brain-Circuit Data Could Lead to Schizophrenia Biomarkers

Identification of brain circuits involved in auditory and visual deficits experienced by people with schizophrenia may point to biomarkers that can be used to identify individuals before they have developed full-blown psychosis.

Daniel Javitt, M.D., Ph.D., of the Nathan Kline Institute at New York University School of Medicine, presented research at the annual meeting of the American College of Neuropsychopharmacology last month identifying deficits among patients with schizophrenia in specific brain regions responsible for auditory and visual processing. These brain regions are widely recognized as being associated with cognitive deficits in schizophrenia.

Javitt's research also shows that these deficits appear to be related to inactivation of the NMDA receptor in the brain, which can in turn be stimulated by D-serine, a compound that has been under investigation for its potentially beneficial effects on cognitive deficits.

In one test Javitt and colleagues identified brain circuits in the auditory cortex that account for an auditory function known as “mismatch negativity” (MMN), which refers to the normal brain's capacity to distinguish variations in auditory tones; for instance, in test conditions most people who hear a series of beeps can easily pick out those that are different from the series.

Additionally, Javitt and colleagues have identified deficits in the brain circuits responsible for a fundamental visual processing task referred to as P1; this function allows the normal brain to put disparate visual details into a coherent picture. For instance, when presented with the visual image of a cat behind a window blind, most people can put the fragmented image together mentally and see it for what it is.

Using event-related evoked potentials (neuroelectrical responses to test stimuli) in individuals with chronic schizophrenia who were stabilized on antipsychotic medication, Javitt and colleagues were able to show significant deficits in both MMN and P1.

And these deficits in areas of the brain specifically responsible for auditory and visual processing were related to impairments in the function of the prefrontal cortex and hippocampus, areas of the brain responsible for higher-level functioning.

Impairment of the MMN function, for instance, makes it difficult or impossible for a patient with schizophrenia to pick up on emotional signals in conversation, which are typically conveyed by inflections in tone of voice. Similarly, deficits in the P1 function account for patients' difficulties in reading, which requires the brain to make sense of letters and symbols.

“It's like a house of cards,” Javitt told Psychiatric News. “If the foundation is weak, each successive level of brain function is going to be impaired. That's important to know because if you want to rehabilitate people you have to start at the very basic level to correct sensory-level deficits.

“If you train people on these very basic sensory tasks and repeat it over and over again, you can get improvement in sensory processing and in higher-level processing.”