Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study

Ekaterina Shatalina; Abhishekh H. Ashok; Matthew B. Wall; Matthew M. Nour; Jim Myers; Tiago Reis Marques; Eugenii A. Rabiner; Oliver D. Howes

NeuroImage: Clinical (Jan 2023)

Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study

Ekaterina Shatalina,
Abhishekh H. Ashok,
Matthew B. Wall,
Matthew M. Nour,
Jim Myers,
Tiago Reis Marques,
Eugenii A. Rabiner,
Oliver D. Howes

Affiliations

Ekaterina Shatalina: Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK; Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK; Department of Psychosis, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK
Abhishekh H. Ashok: Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK; Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK; Department of Psychosis, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK; Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK; Department of Radiology, University of Cambridge, Cambridge, UK
Matthew B. Wall: Invicro, London, UK; Faculty of Medicine, Imperial College London, London, UK; Clinical Psychopharmacology Unit, University College London, London, UK
Matthew M. Nour: Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, UK; Wellcome Centre for Human Neuroimaging (WCHN), University College London, London, UK
Jim Myers: Faculty of Medicine, Imperial College London, London, UK
Tiago Reis Marques: Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK; Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK; Department of Psychosis, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK
Eugenii A. Rabiner: Invicro, London, UK; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK
Oliver D. Howes: Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK; Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK; Department of Psychosis, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK; Corresponding author at: Department of Psychosis Studies, Institute of Psychiatry, Psychology, & Neuroscience, King’s College London, 16 De Crespigny Park, London SE5 8AB, UK.

Journal volume & issue: Vol. 39
p. 103481

Abstract

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Background: Reward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. Here, we examined the association between MOR availability and the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. Method: 37 subjects (18 with Schizophrenia with moderate severity negative symptoms and 19 age and sex-matched healthy controls) underwent a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. Participants also had a [11C]-carfentanil PET scan to measure MOR availability. Results: Reward anticipation was associated with increased neural activation in a widespread network of brain regions including the striatum. Patients with schizophrenia had both significantly lower MOR availability in the striatum as well as striatal hypoactivation during reward anticipation. However, there was no association between MOR availability and striatal neural activity during reward anticipation in either patient or controls (Pearson's Correlation, controls df = 17, r = 0.321, p = 0.18, patients df = 16, r = 0.295, p = 0.24). There was no association between anticipation-related neural activation and negative symptoms (r = –0.120, p = 0.14) or anhedonia severity (social r = –0.365, p = 0.14 physical r = –0.120, p = 0.63). Conclusions: Our data suggest reduced MOR availability in schizophrenia might not underlie striatal hypoactivation during reward anticipation in patients with established illness. Therefore, other mechanisms, such as dopamine dysfunction, warrant further investigation as treatment targets for this aspect of the disorder.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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