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Functional MRI Shows Promise for Studying Psychotic Experiences, Testing Treatment

Key findings

  • Like patients with schizophrenia, volunteers who hold a high number of delusional beliefs show hippocampal overactivity
  • Delusional thinking is also associated with perfusion of brain regions that are closely connected with the hippocampus
  • Hippocampal overactivity might be a useful target for testing novel therapeutic interventions
  • PASL, a type of functional MRI, can be used to study at least some aspects of subthreshold psychosis in people who are unaffected by the confounding variables associated with serious mental illness

Research has shown that patients who have psychotic experiences (subthreshold forms of psychosis) are at a small but significant risk of developing psychotic disorders. Psychotic experiences are also of concern because they can impair cognition and daily functioning.

Patients with schizophrenia have abnormally elevated resting activity in the hippocampus, as reflected by blood flow. Researchers in the Schizophrenia Clinical and Research Program at Massachusetts General Hospital, led by Daphne J. Holt, MD, PhD, the program’s co-director, and Rick P.F. Wolthusen, MD, report in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging  that hippocampal overactivity is also linked to subclinical delusions in non-help-seeking volunteers. These findings add to the evidence that hippocampal overactivity could be a target for testing new treatments for psychosis.

The study cohort consisted of 77 people who had no history of psychiatric illness, substance dependence or treatment with a psychotropic medication. The subjects completed the Peters et al. Delusions Inventory (PDI), the Beck Depression Inventory and the Spielberger State and Trait Anxiety Inventory.

The subjects then underwent pulsed arterial spin labeling (PASL), a type of functional MRI, which scans of the brain to measure cerebral blood flow in various regions in the hippocampus.

Hippocampal Perfusion Levels Correlate with PDI Scores

The research team found that greater perfusion of the hippocampus directly correlated with higher PDI scores, and therefore a higher number of delusional beliefs. In contrast, there were no correlations between hippocampal perfusion and symptoms of depression or anxiety. Hippocampal perfusion also significantly correlated with the levels of distress associated with delusional beliefs.

In a secondary analysis, the researchers tested for associations between delusional thinking and perfusion of 13 brain regions that are closely connected with the hippocampus. They found significant correlations between total PDI score and perfusion of the thalamus, the caudal anterior and posterior cingulate cortices, the middle and superior temporal cortices and the parahippocampal gyrus.

Besides being used to test therapeutic interventions, the authors note that PASL might be used to study aspects of psychotic experiences in healthy volunteers. That could be a boon to psychiatric research because such subjects do not have the confounding variables typically associated with serious mental illness.

Learn more about the Schizophrenia Clinical and Research Program

Learn more about the Department of Psychiatry

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