Working memory processes and the histamine-3 receptor in schizophrenia: a [11C]MK-8278 PET-fMRI study
Year: 2024
Type: article
Study design: Observational Study
Abstract: RATIONALE: Working memory impairment is a prominent feature of schizophrenia which predicts clinical and functional outcomes. Preclinical data suggest histamine-3 receptor (H3R) expression in cortical pyramidal neurons may have a role in working memory, and post-mortem data has found disruptions of H3R expression in schizophrenia. OBJECTIVES: We examined the role of H3R in vivo to elucidate its role on working memory impairment in schizophrenia. METHODS: C]MK-8278 to measure H3R availability, and employed a task during functional magnetic resonance imaging (fMRI) to assess working memory-evoked brain activation and cognitive task performance, in patients with schizophrenia (n = 12) and matched healthy volunteers (n = 12). We assessed the relationship between H3R availability and both task performance and working memory-evoked brain activation in regions of interest (ROIs), including the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). RESULTS: Patients with schizophrenia showed a strong positive correlation, after corrections for multiple comparisons, between ACC H3R availability and task performance (rho = 0.73, p = 0.007), which was absent in the control group (rho = 0.03, p = 0.94). Further ROI analysis did not find a significant relationship between H3R availability and working memory-evoked brain activation. CONCLUSIONS: These results provide support for the role of H3R on working memory processes in patients with schizophrenia.
Source: Psychopharmacology
Institutions: King's College London, Hammersmith Hospital, MRC London Institute of Medical Sciences, Imperial College London, Medical Research Council, University of Oxford, University College London, University of Padua, Queen Mary University of London, Greater Manchester Mental Health NHS Foundation Trust, University of Manchester, Invicro (United Kingdom)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,190
Funders: Wellcome Trust, Maudsley Charity, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Barts Charity, Dipartimenti di Eccellenza, National Institute for Health and Care Research, King's College London, University of Oxford, Ministero dell’Istruzione, dell’Università e della Ricerca, H. Lundbeck A/S, Medical Research Council
OpenAlex ID: W4405685730