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Background and HypothesisSchizophrenia is increasingly understood as a disorder of brain dysconnectivity. Recently, graph-based approaches such as graph convolutional network (GCN) have been leveraged to explore complex pairwise similarities in imaging features among brain regions, which can reveal abstract and complex relationships within brain networks.Study DesignWe used GCN to investigate topological abnormalities of functional brain networks in schizophrenia. Resting-state functional magnetic resonance imaging data were acquired from 505 individuals with schizophrenia and 907 controls across 6 sites. Whole-brain functional connectivity matrix was extracted for each individual. We examined the performance of GCN relative to support vector machine (SVM), extracted the most salient regions contributing to both classification models, investigated the topological profiles of identified salient regions, and explored correlation between nodal topological properties of each salient region and severity of symptom.Study ResultsGCN enabled nominally higher classification accuracy (85.8%) compared with SVM (80.9%). Based on the saliency map, the most discriminative brain regions were located in a distributed network including striatal areas (ie, putamen, pallidum, and caudate) and the amygdala. Significant differences in the nodal efficiency of bilateral putamen and pallidum between patients and controls and its correlations with negative symptoms were detected in post hoc analysis.ConclusionsThe present study demonstrates that GCN allows classification of schizophrenia at the individual level with high accuracy, indicating a promising direction for detection of individual patients with schizophrenia. Functional topological deficits of striatal areas may represent a focal neural deficit of negative symptomatology in schizophrenia.

Schizophrenia spectrum disorders have heterogeneous outcomes and currently no marker predicts the course of illness. Motor abnormalities (MAs) are inherent to psychosis, the risk of psychosis, symptom severity, and brain alterations. However, the prognostic value of MAs is still unresolved. Here, we provide a systematic review of longitudinal studies on the prognostic role of MAs spanning individuals at clinical high risk for psychosis (CHR), patients with first-episode psychosis (FEP), and chronic schizophrenia. We included 68 studies for a total of 23,630 subjects that assessed neurological soft signs (NSS), hypo- or hyperkinetic movement disorders and/or catatonia as a prognostic factor on clinical and functional outcomes. We found increased levels of MAs, in particular NSS, parkinsonism, and dyskinesia, were related to deteriorating symptomatic and poor functional outcome over time. Collectively, the findings emphasize the clinical, prognostic and scientific relevance of MA assessment and detection in individuals with or at risk of psychosis. In the future, instrumental measures of MA are expected to further augment detection, early intervention and treatment strategies in psychosis.

Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. Methods: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Findings: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94–1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ 2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. Interpretation: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Funding: Lundbeck and Otsuka.