Tanja Veselinović1,2, Ingo Vernaleken3,4, Hildegard Janouschek5,6, Paul Cumming7, Michael Paulzen3,4,8, Felix M Mottaghy9,10, Gerhard Gründer11. 1. Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. tveselinovic@ukaachen.de. 2. Jülich Aachen Research Alliance JARA, Translational Brain Medicine, Jülich, Germany. tveselinovic@ukaachen.de. 3. Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. 4. Jülich Aachen Research Alliance JARA, Translational Brain Medicine, Jülich, Germany. 5. Department of Psychiatry and Iowa Neuroscience Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA. 6. Department of Neurology, Medical Faculty, RWTH Aachen University, Aachen, Germany. 7. School of Psychology and Counselling and IHBI, Queensland University of Technology, and QIMR-Berghofer Institute, Brisbane, Australia. 8. Alexianer Hospital Aachen, Aachen, Germany. 9. Department of Nuclear Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany. 10. Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands. 11. Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
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.
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 schizophreniapatients 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 schizophreniapatients than in healthy controls.
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