Henrik Nørbak-Emig1,2, Lars H Pinborg3, Jayachandra M Raghava1,4, Claus Svarer3, William F C Baaré5, Peter Allerup6, Lars Friberg7, Egill Rostrup4, Birte Glenthøj1,2, Bjørn H Ebdrup1. 1. a Centre for Neuropsychiatric Schizophrenia Research, CNSR & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre, Glostrup, University of Copenhagen , Denmark. 2. b Faculty of Health and Medical Sciences, Department of Clinical Medicine , University of Copenhagen , Denmark. 3. c Neurobiology Research Unit and Epilepsy Clinic, Rigshospitalet, University of Copenhagen , Denmark. 4. d Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet - Glostrup , University of Copenhagen , Denmark. 5. e Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen , Denmark. 6. f Institute for Education (DPU), Aarhus University , Denmark. 7. g Department of Clinical Physiology and Nuclear Medicine , Bispebjerg Hospital, University of Copenhagen , Denmark.
Abstract
OBJECTIVES: Long-term dopamine D2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D2/3 receptor binding potentials (BPND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment. METHODS: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [123I]epidepride single-photon emission computerised tomography (SPECT), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT. RESULTS: Neither extrastriatal D2/3 receptor BPND at baseline, nor blockade at follow-up, was related to regional cortical volume changes. In post-hoc analyses excluding three patients with cannabis use we found that higher D2/3 receptor occupancy was significantly associated with an increase in right frontal grey matter volume. CONCLUSIONS: The present data do not support an association between extrastriatal D2/3 receptor blockade and extrastriatal grey matter loss in the early phases of schizophrenia. Although inconclusive, our exclusion of patients tested positive for cannabis use speaks to keeping attention to potential confounding factors in imaging studies.
OBJECTIVES: Long-term dopamine D2/3 receptor blockade, common to all antipsychotics, may underlie progressive brain volume changes observed in patients with chronic schizophrenia. In the present study, we examined associations between cortical volume changes and extrastriatal dopamine D2/3 receptor binding potentials (BPND) in first-episode schizophrenia patents at baseline and after antipsychotic treatment. METHODS: Twenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [123I]epidepride single-photon emission computerised tomography (SPECT), and psychopathology assessments before and after 3 months of treatment with either risperidone (N = 13) or zuclopenthixol (N = 9). Twenty healthy controls matched on age, gender and parental socioeconomic status underwent baseline MRI and SPECT. RESULTS: Neither extrastriatal D2/3 receptor BPND at baseline, nor blockade at follow-up, was related to regional cortical volume changes. In post-hoc analyses excluding three patients with cannabis use we found that higher D2/3 receptor occupancy was significantly associated with an increase in right frontal grey matter volume. CONCLUSIONS: The present data do not support an association between extrastriatal D2/3 receptor blockade and extrastriatal grey matter loss in the early phases of schizophrenia. Although inconclusive, our exclusion of patients tested positive for cannabis use speaks to keeping attention to potential confounding factors in imaging studies.
Authors: Karen S Ambrosen; Martin W Skjerbæk; Jonathan Foldager; Martin C Axelsen; Nikolaj Bak; Lars Arvastson; Søren R Christensen; Louise B Johansen; Jayachandra M Raghava; Bob Oranje; Egill Rostrup; Mette Ø Nielsen; Merete Osler; Birgitte Fagerlund; Christos Pantelis; Bruce J Kinon; Birte Y Glenthøj; Lars K Hansen; Bjørn H Ebdrup Journal: Transl Psychiatry Date: 2020-08-10 Impact factor: 6.222