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Psychopharmacology

, Volume 235, Issue 8, pp 2221–2232 | Cite as

The role of striatal dopamine D2/3 receptors in cognitive performance in drug-free patients with schizophrenia

  • Tanja Veselinović
  • Ingo Vernaleken
  • Hildegard Janouschek
  • Paul Cumming
  • Michael Paulzen
  • Felix M. Mottaghy
  • Gerhard Gründer
Original Investigation

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.

Keywords

Cognitive impairments Schizophrenia Striatum Dopamine D2/3 receptors 

Notes

Funding information

This study was supported by the German Research Association (Deutsche Forschungsgemeinschaft, DFG; KFO-112/2-1).

Compliance with ethical standards

Conflict of interest

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.

Supplementary material

213_2018_4916_MOESM1_ESM.pdf (50 kb)
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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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychiatry, Psychotherapy and Psychosomatics, Medical FacultyRWTH Aachen UniversityAachenGermany
  2. 2.Jülich Aachen Research Alliance JARA, Translational Brain MedicineJülichGermany
  3. 3.Department of Psychiatry and Iowa Neuroscience Institute, Roy J and Lucille A Carver College of MedicineUniversity of IowaIowa CityUSA
  4. 4.Department of Neurology, Medical FacultyRWTH Aachen UniversityAachenGermany
  5. 5.School of Psychology and Counselling and IHBIQueensland University of Technology, and QIMR-Berghofer InstituteBrisbaneAustralia
  6. 6.Alexianer Hospital AachenAachenGermany
  7. 7.Department of Nuclear Medicine, Medical FacultyRWTH Aachen UniversityAachenGermany
  8. 8.Department of Radiology and Nuclear MedicineMaastricht University Medical Center (MUMC+)MaastrichtThe Netherlands
  9. 9.Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany

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