MedWire News: Variations in the dopamine transporter gene ordinarily affect insular, cingulate, and striatal function during an executive task, but the impact on activation is altered in patients with schizophrenia, UK scientists have discovered.

Previous studies have shown that regulation of central dopaminergic transmission, which modulates cognitive processing, is affected by the dopamine transporter gene, and that dopamine function disruption and impaired executive processing are central features of schizophrenia.

To determine the impact of a dopamine transporter gene polymorphism on brain function during executive processing, Diana Prata, from King’s College London, and colleagues performed functional magnetic resonance imaging on 41 schizophrenia patients and 44 healthy individuals during a verbal fluency task.

Genotyping for tandem repeats in the 3’ untranslated region revealed that 18 patients were nine-repeat carriers, while 23 patients were 10-repeat homozygotes. Among controls, 18 were nine-repeat carriers and 26 were 10-repeat homozygotes.

As expected, patients made significantly more errors on the verbal fluency task than controls. Patients with the 10/10 repeat also had a trend for worse performance on the task than nine-repeat carrier patients, with the opposite pattern seen in healthy controls.

The team reports in the Archives of General Psychiatry that the 10-repeat allele was significantly associated with greater activation in the left anterior insula and right caudate nucleus than the nine-repeat allele, regardless of diagnosis. There was also a trend for greater activation in the right insula and greater deactivation in the rostral anterior cingulate cortex associated with the 10-repeat allele.

Interestingly, in patients, the nine-repeat allele was significantly associated with greater activation in the left frontal gyrus than the 10-repeat allele. There were no significant differences in activation detected in healthy controls. Among controls, the 10-repeat allele was significantly associated with greater activation in the left nucleus accumbens than the nine-repeat allele, a pattern that was reversed in patients.

The team notes: “Greater prefrontal activation in schizophrenia during cognitive tasks after controlling for differential performance may reflect impaired prefrontal cortical efficiency.”

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