White Matter Correlates of Theory of Mind in Patients With First-Episode Psychosis

Abstract

Deficits in theory of mind (ToM) are considered as a distinctive feature of schizophrenia. Functional magnetic resonance imaging (fMRI) studies have suggested that aberrant activity among the regions comprising the mentalizing network is related to observed ToM deficits. However, the white matter structures underlying the ToM functional network in schizophrenia remain unclear. To investigate the relationship between white matter integrity and ToM impairment, 35 patients with first-episode psychosis (FEP) and 29 matched healthy controls (HCs) underwent diffusion tensor imaging (DTI). Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) values of the two regions of interest (ROI)–the cingulum and superior longitudinal fasciculus (SLF)–were acquired, and correlational analysis with ToM task scores was performed. Among the patients with FEP, ToM strange story scores were positively correlated with the FA values of the left cingulum and left SLF. There was no significant correlation between FA and ToM task scores in HCs. These results suggest that the left cingulum and SLF constitute a possible neural basis for ToM deficits in schizophrenia. Our study is the first to demonstrate the white matter connectivity underlying the mentalizing network, as well as its relation to ToM ability in patients with FEP.

White matter microstructure and the clinical risk for psychosis: A diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk

“…Indeed, the existing evidence for the involvement of WM deficits in schizophrenia seems robust ( Kubicki et al, 2007 , Tamnes and Agartz, 2016 , Vitolo et al, 2017 ), with the largest-to-date ENIGMA consortium meta-analysis (2359 controls, 1963 patients) reporting widespread microstructural abnormalities across all major WM fasciculi ( Kelly et al, 2018 ). Beyond to between-group differences from healthy controls (HC), numerous studies have identified significant associations between WM markers and (predominantly positive) symptoms ( Bopp et al, 2017 , Cheung et al, 2011 , Stämpfli et al, 2019 ), core cognitive functions ( Kochunov et al, 2017 ), but also theory of mind abilities ( Kim et al, 2021 ) and poor insight into illness ( Antonius et al, 2011 , Gerretsen et al, 2019 ). These associations were especially evident for frontal, fronto-temporal, and fronto-limbic tracts, the superior longitudinal fasciculus, and inter-hemispheric connections ( Kuswanto et al, 2012 , Parnanzone et al, 2017 ).…”

Integrating Clinical Neuropsychology and Psychotic Spectrum Disorders: A Systematic Analysis of Cognitive Dynamics, Interventions, and Underlying Mechanisms

“…Studies [32,60,62,[64][65][66][67][68]72,74,78,80,81,90,[94][95][96][98][99][100][101][102] delve into cognitive impairments, brain structure changes, and neurobiological markers. Key findings include the diagnostic and prognostic significance of mismatch negativity (MMN), neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups.…”

“…Studies [60,62,[64][65][66][67][68]72,74,78,80,81,90,[94][95][96][98][99][100][101][102] evaluate intervention strategies, emphasizing early detection, monitoring of at-risk youth, and the potential for individualized treatments based on neuroprogressive patterns.…”

“…Research [64,[66][67][68][69]72,74,[78][79][80][81]90,[94][95][96][97][98][99][100][101][102] discusses the impact of genetic and environmental factors. Findings suggest shared neurodevelopmental pathways, the significance of early areas of overlap, and the importance of considering psychotic features and medication status.…”

Connecting Neurobiological Features with Interregional Dysconnectivity in Social-Cognitive Impairments of Schizophrenia

“…Moreover, abnormal integrity of the inferior fronto-occipital fasciculus, whose fibers contribute to face perception and mentalizing, is correlated with social deficits in 22q11.2 deletion syndrome, a genetic condition conferring increased risk for SZ (Olszewski et al, 2017). Likewise, decreased integrity of the cingulum, which allows connection within the mentalizing network, and the longitudinal fasciculus have been associated with lower performance in the theory of mind task in SZ patients (Kim et al, 2021). Additionally, reduced integrity of the unicate fasciculus, a white matter bundle connecting the AMY to the OFC and important for the regulation of emotions, correlated with decreased ability to process emotions in SZ patients (Singh et al, 2016;Ho et al, 2019& Jung et al, 2020.…”