The role of striatal dopamine D-2/3 receptors in cognitive performance in drug-free patients with schizophrenia

A considerable body of research links cognitive function to dopaminergic transmission in the prefrontal cortex, but less is known about cognition in relation to striatal dopamine D-2/3 receptors in unmedicated patients with psychosis. We investigated this association by obtaining PET recordings with the high-affinity D-2/3 antagonist ligand [F-18] fallypride in 15 medication-free patients with schizophrenia and 11 healthy controls. On the day of PET scanning, we undertook comprehensive neuropsychological testing and assessment of psychopathology using the Positive and Negative Syndrome Scale (PANSS). The patients' performance in cognitive tests was significantly impaired in almost all domains. Irrespective of medication history, the mean [F-18] fallypride binding potential (BP (ND) ) in the patient group tended to be globally 5-10% higher than that of the control group, but without reaching significance in any brain region. There were significant positive correlations between individual patient performance in the Trail Making Test (TMT(A) and TMT(B)) and Digit-Symbol-Substitution-Test with regional [F-18] fallypride BP (ND) , which remained significant after Bonferroni correction for the TMT(A) in caudate nucleus (CN) and for the TMT(B) in CN and putamen. No such correlations were evident in the control group. The association between better cognitive performance and greater BP (ND) in schizophrenia patients may imply that relatively lower receptor occupancy by endogenous dopamine favors better sparing of cognitive function. Absence of comparable correlations in healthy controls could indicate a greater involvement of signaling at dopamine D-2/3 receptors in certain cognitive functions in schizophrenia patients than in healthy controls.