Negative symptoms in First-Episode Schizophrenia related to morphometric alterations in orbitofrontal and superior temporal cortex: The OPTiMiSE study

Arsime Demjaha*, Silvana Galderisi, Birthe Glenthøj, Celso Arango, Armida Mucci, Andrew Lawrence, Owen O'Daly, Matthew Kempton, Simone Ciufolini, Lone Baandrup, Bjørn H. Ebdrup, Roberto Rodriguez-Jimenez, Maria Diaz-Marsa, Covadonga Martinez Díaz-Caneja, Inge Winter Van Rossum, Rene Kahn, Paola Dazzan, Philip McGuire

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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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.

Original languageEnglish
JournalPsychological Medicine
Early online date24 Feb 2022
DOIs
Publication statusE-pub ahead of print - 24 Feb 2022

Keywords

  • Cortical thickness
  • first-episode psychosis
  • FreeSurfer
  • negative symptoms
  • voxel-based morphometry

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