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Increased resting activity in hippocampus, midbrain, basal ganglia may indicate high psychosis risk

High risk for psychosis was associated with increased resting activity in the hippocampus, midbrain and basal ganglia, and subsequent resolution of high-risk state was associated with normalization of activity in these areas.

“Recent investigations using animal models suggest that the development of psychosis is associated with increased resting activity in the hippocampal region, and that this is linked to an increase in efferent activity in local glutamatergic neurons that project to the basal ganglia and midbrain, elevating activity in areas responsible for dopamine signaling,” Paul Allen, PhD, of King’s College London, and colleagues wrote. “Animal models would thus predict that, prior to the onset of psychosis in humans, resting activity may be elevated in the hippocampus, midbrain, and striatum.”

To examine this association in humans, researchers measured resting perfusion in the hippocampus, basal ganglia and midbrain in individuals at high risk for psychosis. They used pseudo-continuous arterial spin labeling imaging to measure resting regional cerebral blood flow in 52 individuals at ultra-high risk for psychosis and 27 healthy volunteers. Psychotic symptom severity was assessed via the Comprehensive Assessment of At-Risk Mental States. Ultra-high risk individuals were reassessed after a mean of 17 months.

At baseline, ultra-high risk individuals exhibited elevated resting regional cerebral blood flow in the hippocampus, basal ganglia and midbrain, compared with healthy volunteers.

At follow-up, researchers observed symptom improvement and reduced resting regional cerebral blood flow in the hippocampus and ventral striatum among ultra-high risk individuals.

Individuals whose symptoms resolved such that they no longer met ultra-high risk criteria exhibited longitudinal reduction in left hippocampal resting regional cerebral blood flow. This reduction was not observed among individuals who remained at a high-risk state or became psychotic, according to researchers.

“People at high risk for psychosis have increased resting perfusion in the hippocampus, midbrain and striatum, and symptomatic remission in this group is associated with a normalization of perfusion in these regions. The findings are consistent with animal models that propose that psychotic symptoms develop as a consequence of hyperactivity in the hippocampus and striatum,” the researchers concluded. – by Amanda Oldt

Disclosure: Allen reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.