No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

Abstract

Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [¹¹C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (β = 0.013-0.074, partial r = -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BF_H0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

Fig. 1. Relationship between [¹¹C]FLB 457 BP_ND values and age-corrected cognitive test scores for the confirmatory analyses.

Blue circles indicate HC, red triangles indicate FEP. The gray area indicates a 95% confidence interval for the regression line. a BP_ND in DLPFC and verbal learning, b BP_ND in the hippocampus and verbal learning, c BP_ND in DLPFC and working memory, d BP_ND in DLPFC and speed of processing.