Abstract
Objective
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 D2/3 receptors in unmedicated patients with psychosis.
Methods
We investigated this association by obtaining PET recordings with the high-affinity D2/3 antagonist ligand [18F] 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).
Results
The patients’ performance in cognitive tests was significantly impaired in almost all domains. Irrespective of medication history, the mean [18F] fallypride binding potential (BPND) 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 [18F] fallypride BPND, 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.
Discussion
The association between better cognitive performance and greater BPND 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 D2/3 receptors in certain cognitive functions in schizophrenia patients than in healthy controls.
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This study was supported by the German Research Association (Deutsche Forschungsgemeinschaft, DFG; KFO-112/2-1).
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Dr. Vernaleken has served on the speakers’ bureau of Bristol-Myers Squibb (New York, NY), Eli Lilly (Indianapolis, Ind), and GlaxoSmithKline (London, UK). Dr. Gründer has served as a consultant for Allergan (Dublin, Ireland), Boehringer Ingelheim (Ingelheim, Germany), Eli Lilly (Indianapolis, Ind, USA), Janssen-Cilag (Neuss, Germany), Lundbeck (Copenhagen, Denmark), Ono Pharmaceuticals (Osaka, Japan), Otsuka (Chiyoda, Japan), Recordati (Milan, Italy), Roche (Basel, Switzerland), Servier (Paris, France), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Eli Lilly, Janssen Cilag, Neuraxpharm (Langenfeld, Germany), Roche, Servier, and Trommsdorf (Aachen, Germany). He has received grant support from Boehringer Ingelheim and Roche. He is co-founder of Mind and Brain Institute GmbH (Zornheim, Germany) and Brainfoods GmbH (Zornheim, Germany). Dr. Veselinović, Dr. Janouschek, Prof. Cumming, Dr. Paulzen, and Dr. Mottaghy declare no conflicts of interest.
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Figure 1
Scatter plots showing the distributions of the D2/3 receptor availability ([18F]fallypride BPND) in the patients and the controls. Depicted are values for two striatal regions (caudate nucleus, putamen) and two extrastriatal regions (inferior temporal gyrus, thalamus). (PDF 49 kb)
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Veselinović, T., Vernaleken, I., Janouschek, H. et al. The role of striatal dopamine D2/3 receptors in cognitive performance in drug-free patients with schizophrenia. Psychopharmacology 235, 2221–2232 (2018). https://doi.org/10.1007/s00213-018-4916-6
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DOI: https://doi.org/10.1007/s00213-018-4916-6