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IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.ConclusionOn this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

IntroductionGlutamatergic dysfunction is implicated in the pathophysiology of schizophrenia. It is unclear whether glutamatergic dysfunction predicts response to treatment or if antipsychotic treatment influences glutamate levels. We investigated the effect of antipsychotic treatment on glutamatergic levels in the anterior cingulate cortex (ACC), and whether there is a relationship between baseline glutamatergic levels and clinical response after antipsychotic treatment in people with first episode psychosis (FEP).Materials and methodsThe sample comprised 25 FEP patients; 22 completed magnetic resonance spectroscopy scans at both timepoints. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).ResultsThere was no significant change in glutamate [baseline 13.23 ± 2.33; follow-up 13.89 ± 1.74; t(21) = −1.158, p = 0.260], or Glx levels [baseline 19.64 ± 3.26; follow-up 19.66 ± 2.65; t(21) = −0.034, p = 0.973]. There was no significant association between glutamate or Glx levels at baseline and the change in PANSS positive (Glu r = 0.061, p = 0.777, Glx r = −0.152, p = 0.477), negative (Glu r = 0.144, p = 0.502, Glx r = 0.052, p = 0.811), general (Glu r = 0.110, p = 0.607, Glx r = −0.212, p = 0.320), or total scores (Glu r = 0.078, p = 0.719 Glx r = −0.155, p = 0.470).ConclusionThese findings indicate that treatment response is unlikely to be associated with baseline glutamatergic metabolites prior to antipsychotic treatment, and there is no major effect of antipsychotic treatment on glutamatergic metabolites in the ACC.

Introduction: Early Intervention for a first episode of Psychosis (EI) is essential to improve outcomes. There is limited research describing real-world implementation of EI services.Method: Analysis of service characteristics, outcomes (described through a retrospective 2007–2017 Electronic Health Record (EHR) cohort study) and clinical research relating to the first 20 years of implementation of EI services in South London and Maudsley (SLaM) Trust.Results: SLaM EI are standalone services serving 443,050 young individuals in South-London, where (2017) incidence of psychosis (58.3–71.9 cases per 100,000 person-years) is greater than the national average. From 2007–2017 (when the EHR was established), 1,200 individuals (62.67% male, mean age 24.38 years, 88.17% single; two-thirds of non-white ethnicity) received NICE-compliant EI care. Pathways to EI services came mainly (75.26%) through inpatient (39.83%) or community (19.33%) mental health services or Accident and Emergency departments (A&E) (16%). At 6 year follow-up 34.92% of patients were still being prescribed antipsychotics. The 3 month and 6 year cumulative proportions of those receiving clozapine were 0.75 and 7.33%; those compulsorily admitted to psychiatric hospitals 26.92 and 57.25%; those admitted to physical health hospitals 6.83 and 31.17%, respectively. Average 3 months and 6 year days spent in hospital were 0.82 and 1.85, respectively; mean 6 year attendance at A&E was 3.01. SLaM EI clinical research attracted £58 million grant income and numerous high-impact scientific publications.Conclusions: SLaM EI services represent one of the largest, most established services of its kind, and are a leading model for development of similar services in the UK and worldwide.