Ameliorative patterns of grey matter in patients with first-episode and treatment-naïve schizophrenia

Abstract

Background Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear. Methods 343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied. Results Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests. Conclusions In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.

Cortical impoverishment in a stable subgroup of schizophrenia: Validation across various stages of psychosis

“…The neuroanatomical differences between the two clusters varied across the three samples, possibly due to differences in recruitment criteria as well as the sample size differences, which combined with our stringent correction for multiple testing, reduced the likelihood of demonstrating significant regional differences in validation samples. Furthermore, the presence of stage-specific differences in the location of grey matter differences (i.e., the duration of illness effect) from age-and sex-matched healthy cohorts is a well-established finding in schizophrenia (Li et al, 2022;Palaniyappan, 2017). While scanning parameters varied across the three studies, it is important to note that both patients and healthy controls were scanned using the same acquisition parameters within each study.…”

Clusters of psychosis: compensation as a contributor to the heterogeneity of schizophrenia

“…34 These excesses appear as devi ations from healthy norms but occur in the presence of better outcomes or less illness burden (i.e., are apparently beneficial or compensatory). A subtle but statistically significant excess of grey matter concentration occurs among patients with consider ably short duration of psychotic illness, 35 which is associated with less severe symptoms and better cognitive profile among untreated patients. 35 Progressive supranormal deviations are also reported among adolescents with subthreshold symptoms for neurodevelopmental markers such as gyrification, 36 a fea ture that may relate to better prognosis at later stages.…”

Language Network Dysfunction and Formal Thought Disorder in Schizophrenia

“…If we assume schizophrenia as a disorder that involves some degree of illness-related brain changes, then concomitant adaptive changes in response to this deficit should be expected, at least in a subset of patients [101,102]. Some of these adaptive changes, in effect, may obscure the construct-to-circuit relationship between the LN and FTD.…”