For Release: January 28, 2009
Contact: dms.communications@dartmouth.edu, 603-650-1492
Altered Brain Activity In Schizophrenia May Exaggerate Self Focus
Dr. Alan Green
Hanover, N.H.—Schizophrenia may blur the boundary between internal and external realities by over-activating a brain system involved in self-reflection, a new brain imaging study has found.
The research links schizophrenia to an abnormal 'default mode' in the brain, expanding the view of a disabling disorder that affects up to one percent of the population. A team based at MIT and Harvard that included a Dartmouth Medical School psychiatrist reports the work in the Jan. 27 Proceedings of the National Academy of Sciences.
Traditionally, the disturbed thoughts, perceptions and emotions characteristic of schizophrenia are considered caused by disconnections among the brain regions that control these different functions. The study found that schizophrenia also triggers excessive connectivity between the so-called default brain regions involved in self-reflection.
This default network becomes active when people are thinking about nothing in particular or about themselves, but is typically suppressed when performing demanding mental tasks. Schizophrenia patients, however, can't seem to turn off the system, apparently causing an exaggerated focus on self.
"These findings help provide a new way to think about the basis for some symptoms we see in patients with schizophrenia, and in the future might also provide a useful method for determining the effectiveness of treatment approaches," said Dr. Alan I. Green, professor and chair of psychiatry at DMS, a member of the research team. "They may also help explain why patients seem at times to attend more to their own thoughts than to things around them," added Green, also a professor of pharmacology and toxicology.
These findings... may also help explain why patients seem at times to attend more to their own thoughts than to things around them.
—Dr. Alan Green
Schizophrenia has a strong genetic component, and first-degree relatives of patients (who share half their genes) are 10 times more likely to develop the disease than the general population. The identities of these genes and their affect on the brain remain largely unknown.
The researchers studied three carefully matched groups of 13 subjects each: schizophrenia patients, nonpsychotic first-degree relatives of patients and healthy controls. They selected patients who were recently diagnosed, so that differences in prior treatment or psychotic episodes would not bias the results.
Functional magnetic resonance imaging (fMRI) scanned subjects while resting and while performing easy or hard memory tasks. The behavioral and clinical testing were performed by Dr. Larry J. Seidman and colleagues at Harvard Medical School, and the imaging data were analyzed by first author Dr. Susan Whitfield-Gabrieli, a research scientist at the MIT Martinos Imaging Center at the McGovern Institute.
The researchers focused on the brain default system partly because it is easy to measure and because it is affected in different ways by different disorders. This default network includes the medial prefrontal cortex and the posterior cingulate cortex, regions that associated with self-reflection and autobiographical memories that become connected into a synchronously active network when the mind is allowed to wander.
In the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, remaining so as they performed the memory tasks. Patients were less able than healthy control subjects to suppress this network activity of during the task. Interestingly, the less the suppression and the greater the connectivity, the worse the patients performed on a difficult memory task, and the more severe their clinical symptoms.
The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant. For instance, if brain regions whose activity normally signifies self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them.
First-degree relatives of schizophrenia patients who did not themselves have the disease also showed an overactive default system, though to a lesser extent. This suggests that overactivation may be linked to the genetic cause of the disease rather than its consequences.
This study was supported by the Mental Illness and Neuroscience Discovery Institute, National Association of Research in Schizophrenia and Depression Stone Award, National Institute of Mental Health, Massachusetts Department of Mental Health's Commonwealth Research Center, the Poitras Center for Affective Disorders Research at the McGovern Institute/MIT and the National Center for Research Resources. Other contributors to the study were John D. Gabrieli, McGovern Institute, MIT; Heidi W. Thermenos, Snezana Milanovic, Robert W. McCarley, Martha E. Shenton and Joanne Wojcik (Harvard Medical School); Ming T. Tsuang (Harvard Institute of Psychiatric Epidemiology and Genetics); Stephen V. Faraone (State University of New York); Alfonso Nieto-Castanon (MIT); and Peter LaViolette (Martinos Center for Biomedical Imaging, (MIT-Harvard).
This information was adapted from a press release by Catherine Delude, distributed by the MIT news office newsoffice@mit.edu.
-DMS-
