Default Mode Network Connectivity Associated with Schizophrenia Severity

By Elizabeth Gardner

Sophia Mueller, M.D.

An imaging marker that measures the severity of chronic schizophrenia could have a significant impact on risk prediction, detection and treatment. Such a marker, discovered through using functional MR imaging to study the brain's resting state, was described Tuesday morning by a team of German researchers.

The research, led by presenter Sophia Mueller, M.D., from Ludwig-Maximilians University, Munich, included members from the Institute of Clinical Radiology and the Department of Psychiatry and Psychotherapy.

"Despite [being an] enormous public health burden, treatments for schizophrenia still rely on a handful of mechanistic insights that date back to the 1960s," Dr. Mueller noted in her abstract. "There is an urgent need to develop more effective clinically applicable strategies for treatment, risk prediction, and prevention. In order to make an imaging marker useful for therapy monitoring and risk prediction, the association [of default mode network, or DMN, connectivity changes] with symptom severity has to be established."

Studying the brain's default mode network, the team obtained functional MRI (fMRI) data from 23 chronic schizophrenia patients and 25 healthy controls. Each subject was scanned for six minutes while awake with eyes shut, and holding the head as still as possible. The subjects were interviewed using the Positive and Negative Symptom Scale (PANSS), a 45-minute clinical assessment that measures symptom severity. Positive symptoms include delusions, hallucinations and grandiosity; negative symptoms include emotional and social withdrawal and difficulty in abstract thinking.

The scans showed distinct differences in DMN connectivity between chronic schizophrenia patients and healthy patients and also differences that correlated to variations in the severity and type of symptoms. Within the DMN, patients with more severe positive symptoms and more severe anxiety had less connectivity in the medial prefrontal cortex. Specifically, positive symptoms were correlated with DMN connectivity of the dorsomedial prefrontal cortex, while trait anxiety was correlated with DMN connectivity of the ventromedial prefrontal cortex. Connectivity between the DMN and the right striatum was negatively correlated with general symptom severity as measured by the PANSS total score. No correlation between severity of negative symptoms and DMN connectivity was detected.

DMN connectivity could serve as an imaging marker to monitor the effects of schizophrenia treatment and also help measure the presence of the disease in patients who carry genes associated with a risk of schizophrenia. The next step in the research is to correlate the MRI findings with the genetic variations that predispose patients to develop schizophrenia.

"This is an important link that we have to make," Dr. Mueller said. The two departments are currently beginning a follow-up study to compare fMRI studies of 100 schizophrenia patients with those of their unaffected relatives who carry genetic risk factors for schizophrenia, and also with a group of healthy controls. Results should be available within the next two years.

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