Early-Stage Schizophrenia Associated With Increased Prefrontal Cortex Connectivity That is Reversed Following Treatment

Early-Stage Schizophrenia Associated With Increased Prefrontal Cortex Connectivity That is Reversed Following Treatment

Posted: January 21, 2015

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Schizophrenia — a disabling brain disorder characterized by psychosis, including hallucinations and delusions — is viewed by many scientists as resulting, at least in part, from too few connections between certain parts of the brain. But a team led by 2012 NARSAD Young Investigator grantee Alan Anticevic, Ph.D., of Yale University, has found patients in the early stages of schizophrenia with increased connectivity in specific brain regions. The research was published online January 7th in The Journal of Neuroscience.

Previous research has associated schizophrenia with dysfunction in the prefrontal cortex (PFC), which works as a kind of “boss” over brain activity by overseeing much of our cognition and behavior. However, most of that research has looked at patients with long-standing schizophrenia. The newly reported research led by Dr. Anticevic is the first published work to characterize PFC functional connectivity among patients with early-course schizophrenia who haven't yet taken any medication; these patients had been experiencing symptoms of schizophrenia for at most a year. Dr. Anticevic’s group conducted the neuroimaging aspect of the study in collaboration with Prof. Qiyong Gong’s team at the Huaxi MR Research Center, whose members studied the patients over the course of time.

By looking at patients prior to beginning medication and reexamining those same patients 12 months later, the researchers made several interesting observations. Compared to people with no history of mental illness, the early-course schizophrenia patients showed a general pattern of increased connectivity unique to medial regions of the PFC. A year later, after the patients had begun taking antipsychotic medication to treat their illness, connectivity levels appeared to have stopped increasing and began to decrease, suggesting that the beginnings of schizophrenia may involve high PFC connectivity that is at least partially reversed with treatment by antipsychotics.

Patients with higher PFC connectivity experienced more severe symptoms. At the 12-month follow up, these patients showed the greatest decline in connectivity, and, importantly, the greatest reduction in their “positive” symptoms. (In schizophrenia, positive symptoms are those including psychosis and hallucination that indicate a loosening grip on reality. So-called “negative” symptoms of the illness include deficits in various aspects of cognitive function.)

Altogether, the findings of Dr. Anticevic’s team point to measurements of PFC connectivity over time as a possible mechanism for diagnosing and treating schizophrenia early on. Rather than the low PFC activity found in later-stage patients, it may be high PFC connectivity that signals the early stages of illness among non-medicated patients.  As pointed our by Dr. Anticevic, this is consistent with pharmacological studies pointing to elevated glutamate levels. Medications that work to restore normal connectivity patterns, he suggests, could be used in such individuals to treat symptoms from those early stages.

One of the next steps in this research is to identify exactly how antipsychotics and other drugs can improve symptoms by changing PFC connectivity.

Read the paper abstract.