Distinct Patterns of Cerebral Cortical Thinning in Schizophrenia: A Neuroimaging Data-Driven Approach

Abstract

Schizophrenia is an etiologically and clinically heterogeneous disorder. Although neuroimaging studies have revealed brain alterations in schizophrenia, most studies have assumed that the disorder is a single entity, neglecting the diversity of alterations observed in the disorder. The current study sought to explore the distinct patterns of altered cortical thickness in patients with schizophrenia and healthy individuals using a data-driven approach. Unsupervised clustering using self-organizing maps followed by a K-means algorithm was applied to regional cortical thickness data in 108 schizophrenia patients and 121 healthy controls. After clustering, the clinical characteristics and cortical thickness patterns of each cluster were assessed. Unsupervised clustering revealed that a 6-cluster solution was the most appropriate in this sample. There was substantial overlap between the patterns of cortical thickness in schizophrenia patients and healthy controls, although the distributions of the patients and controls differed across the clusters. The patterns of altered cortical thickness in schizophrenia exhibited cluster-specific features; patients within a cluster exhibited the most extensive cortical thinning, particularly in the medial prefrontal and temporal regions, while those in other clusters exhibited reduced cortical thickness in the medial frontal region or temporal lobe. Furthermore, in the schizophrenia group, extensive cortical thinning was correlated with a higher dosage of antipsychotic medication, while preserved cortical thickness appeared to be linked to less negative symptoms. This data-driven neuroimaging approach revealed distinct patterns of cortical thinning in schizophrenia, possibly reflecting the etiological heterogeneity of the disorder.

The role of the retinoids in schizophrenia: genomic and clinical perspectives

“…This is consistent with the long-standing neurodevelopmental hypothesis of schizophrenia, whereby an interplay between genetic and environmental factors disturb early neurodevelopment [5][6][7]. This seems to correspond to a reduction of dendritic volume and density, which manifests macroscopically as cortical thinning and reduced neural connectivity [8][9][10]. While early investigation of this hypothesis was focused around the dopamine system, because of its clear role in psychosis, it now seems likely that there are many biological pathways involved in schizophrenia and related psychotic disorders.…”

Mapping cortical surface features in treatment resistant schizophrenia with in vivo structural MRI

“…Neuroimaging studies using high resolution MRI (Magnetic Resonance Imaging) demonstrate widespread differences in patients with schizophrenia in cortical grey matter volume (CV) (Anderson et al, 2015;Molina et al, 2010Molina et al, , 2008Molina et al, , 2005Mouchlianitis et al, 2016;Zugman et al, 2013) cortical thickness (CT) (Heinrichs et al, 2017;Kuperberg et al, 2003;Narr et al, 2005;Nesvåg et al, 2008;Plitman et al, 2016;Rimol et al, 2010;Smiley et al, 2012;Sugihara et al, 2017) and surface area (SA) (Kong et al, 2015;van Haren et al, 2012;Xiao et al, 2015) compared to healthy controls (HC) (Maller et al, 2012;Quarantelli et al, 2014;Selemon and Goldman-Rakic, 1999). CV reductions in patients with schizophrenia are one of the most common findings in the condition, beginning with global grey matter reductions and associated increases in ventricular volume (Emami et al, 2016;Harvey et al, 1993;Honea et al, 2005;Kong et al, 2015;Shergill et al, 2001).…”

The dark side of the mean: brain structural heterogeneity in schizophrenia and its polygenic risk

“…Patients diagnosed with SZ display substantial heterogeneity in terms of their clinical characteristics and symptoms 4 , treatment response 5 and long term prognosis 6 . The notion that the observed heterogeneity stems at least partially from distinct subtypes of patients with differentially affected neurobiology and clinical and cognitive profiles 7-9 , has not been fully confirmed 10 , and the question of whether there is one unifying pathophysiological process shared across patients, or a multitude of disease processes leading to a similar clinical syndrome remains salient 11 .…”