Frontal D2/3 receptor availability in schizophrenia patients before and after their first antipsychotic treatment: Relation to cognitive functions and psychopathology

Abstract

Background: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Methods: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [123I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n = 13) or zuclopenthixol (n = 9), 22 patients were reexamined. Results: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P = .003) and planning time (r = -0.436, P = .048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P = .003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P = .016). Conclusions: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms.