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Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP).
MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses.
The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES −0.213, 95% confidence interval (CI) (−0.344 to −0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES −0.031, 95% CI (−0.048 to −0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ.
There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.
White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.
Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).
Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).
Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.
In recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables.
Altogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR.
Remission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators.
These findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery.