• Henrik Nørbak-Emig, Bjørn H Ebdrup, Birgitte Fagerlund, Claus Svarer, Hans Rasmussen, Lars Friberg, Peter N Allerup, Egill Rostrup, Lars H Pinborg, and Birte Y Glenthøj.
• Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
• Int. J. Neuropsychopharmacol. 2016 May 1; 19 (5).

BackgroundWe 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.MethodsTwenty-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 [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined.ResultsBlockade 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).ConclusionsOur 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.© The Author 2016. Published by Oxford University Press on behalf of CINP.

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