The histamine system and cognitive function: An in vivo H3 receptor PET imaging study in healthy volunteers and patients with schizophrenia

Author:

Arumuham Atheeshaan123ORCID,Nour Matthew M145,Veronese Mattia67,Onwordi Ellis Chika1238,Rabiner Eugenii A79,Howes Oliver D12310

Affiliation:

1. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK

2. Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK

3. Psychiatric Imaging Group, Medical Research Council, London Institute of Medical Sciences, Hammersmith Hospital, London, UK

4. Department of Psychiatry, University of Oxford, Oxford, UK

5. Max Planck University College London Centre for Computational Psychiatry and Ageing Research, London, UK

6. Department of Information Engineering, University of Padua, Padua, Italy

7. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

8. Centre for Psychiatry and Mental Health, Wolfson Institute of Population Health, Queen Mary University of London, London, UK

9. Invicro, London, UK

10. H Lundbeck A/s, St Albans, UK

Abstract

Background: The histamine-3 receptor (H3R) is an auto- and heteroreceptor that inhibits the release of histamine and other neurotransmitters. Post-mortem evidence has found altered H3R expression in patients with psychotic disorders, which may underlie cognitive impairment associated with schizophrenia (CIAS). Aims: We used positron emission tomography (PET) imaging to compare brain uptake of an H3R selective tracer between patients with schizophrenia and matched controls (healthy individuals). Regions of interest included the dorsolateral prefrontal cortex (DLPFC) and striatum. We explored correlations between tracer uptake and symptoms, including cognitive domains. Methods: A total of 12 patients and 12 matched controls were recruited to the study and were assessed with psychiatric and cognitive rating scales. They received a PET scan using the H3R-specific radioligand [11C]MK-8278 to determine H3R availability. Results: There was no statistically significant difference in tracer uptake between patients and controls in the DLPFC ( t19 = 0.79, p = 0.44) or striatum (t21 = 1.18, p = 0.25). An exploratory analysis found evidence for lower volume of distribution in the left cuneus (pFWE-corrected = 0.01). DLPFC tracer uptake was strongly correlated with cognition in controls (trail making test (TMT) A: r = 0.77, p = 0.006; TMT B: rho = 0.74, p = 0.01), but not in patients (TMT A: r = −0.18, p = 0.62; TMT B: rho = −0.06, p = 0.81). Conclusions: These findings indicate H3R in the DLPFC might play a role in executive function and this is disrupted in schizophrenia in the absence of major alterations in H3R availability as assessed using a selective radiotracer for H3R. This provides further evidence for the role of H3R in CIAS.

Publisher

SAGE Publications

Subject

Pharmacology (medical),Psychiatry and Mental health,Pharmacology

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