Arsime Demjaha1,2, Silvana Galderisi3, Birthe Glenthøj4, Celso Arango5, Armida Mucci3, Andrew Lawrence1,2, Owen O'Daly6, Matthew Kempton1,2, Simone Ciufolini1,2, Lone Baandrup4, Bjørn H Ebdrup4, Roberto Rodriguez-Jimenez5, Maria Diaz-Marsa5, Covadonga Martinez Díaz-Caneja5, Inge Winter van Rossum7, Rene Kahn7,8, Paola Dazzan1,2, Philip McGuire1,2. 1. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 2. National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. 3. Department of Psychiatry, University of Campania Luigi Vanvitelli, Caserta, Italy. 4. Faculty of Health and Medical Sciences, Department of Clinical Medicine, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Center Glostrup, University of Copenhagen, Copenhagen, Denmark. 5. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health. Hospital General Universitario Gregorio Marañón. IiSGM, CIBERSAM. School of Medicine, Universidad Complutense de Madrid,Madrid,Spain. 6. Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK. 7. Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, Netherlands. 8. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES). METHODS: T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed). RESULTS: The presence of PMN symptoms was associated with larger left inferior orbitofrontal volume (p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus (p = 0.007), but reduced CTh in the left superior temporal gyrus (p = 0.009). CONCLUSIONS: The findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.
BACKGROUND: Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES). METHODS: T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed). RESULTS: The presence of PMN symptoms was associated with larger left inferior orbitofrontal volume (p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus (p = 0.007), but reduced CTh in the left superior temporal gyrus (p = 0.009). CONCLUSIONS: The findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.
Authors: Zetao Huang; Dun Ruan; Bingjie Huang; Tianhang Zhou; Chuan Shi; Xin Yu; Raymond C K Chan; Yi Wang; Chengcheng Pu Journal: Front Psychiatry Date: 2022-09-26 Impact factor: 5.435