Elevated intrinsic cortical curvature in treatment-resistant schizophrenia: Evidence of structural deformation in functional connectivity areas and comparison with alternate indices of structure

Edgardo Torres-Carmona; Fumihiko Ueno; Yusuke Iwata; Shinichiro Nakajima; Jianmeng Song; Wanna Mar; Ali Abdolizadeh; Sri Mahavir Agarwal; Vincenzo de Luca; Gary Remington; Philip Gerretsen; Ariel Graff-Guerrero

doi:10.1016/j.schres.2024.05.002

Elevated intrinsic cortical curvature in treatment-resistant schizophrenia: Evidence of structural deformation in functional connectivity areas and comparison with alternate indices of structure

Schizophr Res. 2024 May 17:269:103-113. doi: 10.1016/j.schres.2024.05.002. Online ahead of print.

Affiliations

¹ Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
² Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
³ Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Neuropsychiatry, Keio University, Minato, Tokyo, Japan.
⁴ Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Institute Research Program, CAMH, Toronto, ON, Canada.
⁵ Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Institute Research Program, CAMH, Toronto, ON, Canada.
⁶ Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Institute Research Program, CAMH, Toronto, ON, Canada. Electronic address: Ariel.Graff@camh.ca.

PMID: 38761434
DOI: 10.1016/j.schres.2024.05.002

Abstract

Background: Research suggests structural and connectivity abnormalities in patients with treatment-resistant schizophrenia (TRS) compared to first-line responders and healthy-controls. However, measures of these abnormalities are often influenced by external factors like nicotine and antipsychotics, limiting their clinical utility. Intrinsic-cortical-curvature (ICC) presents a millimetre-scale measure of brain gyrification, highly sensitive to schizophrenia differences, and associated with TRS-like traits in early stages of the disorder. Despite this evidence, ICC in TRS remains unexplored. This study investigates ICC as a marker for treatment resistance in TRS, alongside structural indices for comparison.

Methods: We assessed ICC in anterior cingulate, dorsolateral prefrontal, temporal, and parietal cortices of 38 first-line responders, 30 clozapine-resistant TRS, 37 clozapine-responsive TRS, and 52 healthy-controls. For comparative purposes, Fold and Curvature indices were also analyzed.

Results: Adjusting for age, sex, nicotine-use, and chlorpromazine equivalence, principal findings indicate ICC elevations in the left hemisphere dorsolateral prefrontal (p < 0.001, η2partial = 0.142) and temporal cortices (LH p = 0.007, η2partial = 0.060; RH p = 0.011, η2partial = 0.076) of both TRS groups, and left anterior cingulate cortex of clozapine-resistant TRS (p = 0.026, η2partial = 0.065), compared to healthy-controls. Elevations that correlated with reduced cognition (p = 0.001) and negative symptomology (p < 0.034) in clozapine-resistant TRS. Fold and Curvature indices only detected group differences in the right parietal cortex, showing interactions with age, sex, and nicotine use. ICC showed interactions with age.

Conclusion: ICC elevations were found among patients with TRS, and correlated with symptom severity. ICCs relative independence from sex, nicotine-use, and antipsychotics, may support ICC's potential as a viable marker for TRS, though age interactions should be considered.

Keywords: Freesurfer; Gaussian curvature; Intrinsic cortical curvature; MRI; Schizophrenia; Treatment-resistance.