Abstract
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. 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. 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. 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.
Highlights
Progressive loss of grey matter (GM) tissue is one of the presumed pathophysiological processes targeted by the paradigm of ‘early intervention’ in psychosis (Lieberman, Small, & Girgis, 2019; Palaniyappan, 2021)
We investigate the effects of the duration of untreated illness, symptom burden and cognitive function across multiple domains to address the question of compensatory cortical reorganisation characterised by concurrent Grey matter (GM) deficits and excesses in schizophrenia
Patients scanned with the GE system were more symptomatic than the other group scanned with the Phillips scanner, but there were no differences in age, duration of the untreated psychosis (DUP) or neurocognition
Summary
Progressive loss of grey matter (GM) tissue is one of the presumed pathophysiological processes targeted by the paradigm of ‘early intervention’ in psychosis (Lieberman, Small, & Girgis, 2019; Palaniyappan, 2021). Several longitudinal observations report a progressive loss of GM in patients with schizophrenia, occurring at a rate greater than expected from healthy individuals (Vita, De Peri, Deste, & Sacchetti, 2012). This lower GM appears to be spatially constrained to key cortical regions (frontoinsular and temporal cortex), and temporally limited to the period immediately after the first episode (Palaniyappan, 2017). Meta-analytic evidence of cross-sectional studies indicates that while some regional GM changes persist or expand in chronic schizophrenia, others ameliorate, ‘closing the gap’ with healthy controls (HC) (Liloia et al, 2021) Taken together, these findings support a process of reorganisation characterised by concurrent GM loss as well as gain in schizophrenia. 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
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