TY - JOUR
T1 - Negative symptoms in First-Episode Schizophrenia related to morphometric alterations in orbitofrontal and superior temporal cortex: the OPTiMiSE study
AU - Demjaha, Arsime
AU - Galderisi, Silvana
AU - Glenthøj, Birte Yding
AU - Arango, Celso
AU - Mucci, Armida
AU - Lawrence, Andrew
AU - O'Daly, Owen
AU - Kempton, Matthew
AU - Ciufolini, Simone
AU - Baandrup, Lone
AU - Ebdrup, Bjørn H
AU - Rodriguez-Jimenez, Roberto
AU - Diaz-Marsa, Maria
AU - Díaz-Caneja, Covadonga Martinez
AU - Winter van Rossum, Inge
AU - Kahn, Rene
AU - Dazzan, Paola
AU - McGuire, Philip
PY - 2023/6/24
Y1 - 2023/6/24
N2 - 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.
AB - 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.
KW - Antipsychotic Agents/therapeutic use
KW - Brain
KW - Gray Matter/pathology
KW - Humans
KW - Magnetic Resonance Imaging/methods
KW - Schizophrenia/drug therapy
KW - Temporal Lobe/diagnostic imaging
UR - http://www.scopus.com/inward/record.url?scp=85125530932&partnerID=8YFLogxK
U2 - 10.1017/S0033291722000010
DO - 10.1017/S0033291722000010
M3 - Journal article
C2 - 35197142
SN - 0033-2917
VL - 53
SP - 3471
EP - 3479
JO - Psychological Medicine
JF - Psychological Medicine
IS - 8
ER -