Dampened reward response tied to schizophrenia risk

By Eleanor McDermid, Senior medwireNews Reporter

The striatal hypoactivation during reward anticipation seen in patients with schizophrenia is also present in their unaffected first-degree relatives, research shows.

Furthermore, the effect was also present in mentally healthy controls who had a genetic mutation linked to schizophrenia risk, report Andreas Meyer-Lindenberg (Institute of Mental Health Mannheim, Germany) and co-workers in JAMA Psychiatry.

Striatal response during reward anticipation may therefore be a promising intermediate endophenotype for schizophrenia, they say.

“Supporting the utility of this phenotype, we found that striatal function could be measured reliably and was not confounded with potential preexisting structural abnormalities in the striatum, differences in task performance, or head motion”, writes the team.

In the study, 54 mentally healthy first-degree relatives of schizophrenia patients underwent functional magnetic resonance imaging while undertaking a monetary incentive task. Compared with 80 mentally healthy controls, the relatives had significant hypoactivation in the left and right ventral striatum during the task.

Hypoactivation occurred when trying to win money and when trying to avoid losing money, but not during either of the control conditions (verbal feedback or neutral). The relatives had similar reaction times during the task to the controls, and striatal activation did not correlate with striatal grey matter volume.

“Our data therefore support the hypothesis that striatal abnormalities related to schizophrenia risk are primarily functional, consistent with our prior findings indicating that striatal volume abnormalities are not heritable”, say the researchers.

The relatives and controls were well matched on demographic variables, and on most measures of psychosis and neurocognition. The exception was for the Trail-Making Test part B (TMT-B), in which relatives were significantly slower than controls. Across all participants, greater striatal activation during reward anticipation correlated with better performance on the TMT-B.

The team also looked at the effect of the NRG1 rs10503929 mutation in 78 of the controls, finding that those who were homozygous for the schizophrenia risk allele (T) had significantly lower striatal activation during the reward anticipation task than those who carried the C allele.

Meyer-Lindenberg and colleagues say their results are a starting point in the search for mechanisms that could cause striatal hypoactivation, such as altered dopamine and glutamate neurotransmission.

“In addition, because risk mechanisms are attractive systems-level targets for early treatment and prevention, the effect of established and novel treatments on this circuitry should be further investigated and explored for genetic contributions”, they conclude.

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