Mesostriatal Dopaminergic Circuit Dysfunction in Schizophrenia: A Multimodal Neuromelanin-Sensitive Magnetic Resonance Imaging and [ 18 F]-DOPA Positron Emission Tomography Study.
| Autor: | Vano LJ; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom. Electronic address: luke.vano@kcl.ac.uk., McCutcheon RA; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, United Kingdom., Rutigliano G; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom., Kaar SJ; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Division of Psychology and Mental Health, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom., Finelli V; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom., Nordio G; Department of Neuroimaging, King's College London, London, United Kingdom., Wellby G; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom., Sedlacik J; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Mansfield Centre for Innovation - MR Facility, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom., Statton B; Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Mansfield Centre for Innovation - MR Facility, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, United Kingdom., Rabiner EA; Invicro, London, United Kingdom; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom., Ye R; Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, United Kingdom; The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, China., Veronese M; Department of Neuroimaging, King's College London, London, United Kingdom; Department of Information Engineering, University of Padua, Padova, Italy., Hopkins SC; Sumitomo Pharma America, Inc., Marlborough, Massachusetts., Koblan KS; Sumitomo Pharma America, Inc., Marlborough, Massachusetts., Everall IP; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom., Howes OD; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom. Electronic address: oliver.howes@kcl.ac.uk. |
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| Jazyk: | angličtina |
| Zdroj: | Biological psychiatry [Biol Psychiatry] 2024 Oct 15; Vol. 96 (8), pp. 674-683. Date of Electronic Publication: 2024 Jun 26. |
| DOI: | 10.1016/j.biopsych.2024.06.013 |
| Abstrakt: | Background: Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin (NM)-sensitive magnetic resonance imaging provides a marker of long-term dopamine function. We examined whether midbrain NM-sensitive magnetic resonance imaging contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia than in healthy control (HC) participants and whether this correlated with dopamine synthesis capacity. Methods: One hundred fifty-four participants (schizophrenia group: n = 74, HC group: n = 80) underwent NM-sensitive magnetic resonance imaging of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n = 38) also received [ 18 F]-DOPA positron emission tomography to measure dopamine synthesis capacity (K Results: SN-VTA NM-CNR was significantly higher in patients with schizophrenia than in HC participants (effect size = 0.38, p = .019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA K Conclusions: Our results suggest that NM levels are higher in patients with schizophrenia than in HC individuals, particularly in midbrain regions that project to parts of the striatum that receive innervation from the limbic and association cortices. The direct relationship between measures of NM and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and thus as potential therapeutic targets. (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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