Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown.

We searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using 18FDG-PET, in schizophrenia/first-episode psychosis v. controls. Effect sizes (Hedges g) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus.

Thirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's g = −0.74 ± 0.54, p = 0.01; I2 = 67%) and metabolism relative to whole brain (g = −0.44 ± 0.34, p = 0.01; I2 = 55%) were lower in schizophrenia v. controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic (g = −1.18 ± 0.73) v. first-episode patients (g = −0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (−1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia v. controls (−0.25 ± 0.24, p = 0.049; I2 = 5%). Studies identified reporting voxel-based morphometry measures of absolute 18FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower 18FDG uptake in the left anterior cingulate gyrus (Z = −4.143; p = 0.007) and the left inferior orbital frontal gyrus (Z = −4.239; p = 0.02) in schizophrenia.

We report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.

Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.

The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.

This was a naturalistic study of community patients recommended for clozapine treatment.

Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).

These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation.

We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change.

Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12–1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10–1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09–1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12–1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06–1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01–1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09–1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00–1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes.

Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.

Evidence from genetics, post mortem and animal studies suggest that N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction has an important role in the pathophysiology of psychosis. However, it is not known if NMDAR activity is altered in the early stages of psychosis or if this links to symptom severity. Our aim was to investigate NMDAR availability in first-episode psychosis (FEP) and determine if it links to symptom severity. The NMDAR hypofunction hypothesis of schizophrenia was initially proposed in the 1990s on the basis of observations that ketamine and phencyclidine (PCP) induced the full range of schizophrenia-like symptoms (positive, negative and cognitive) when given to healthy participants and also that they worsen symptoms in patients with schizophrenia.

We recruited 40 volunteers, including 21 patients with schizophrenia from early intervention services in London (12 antipsychotic-free and 9 receiving antipsychotic medication) and 19 matched healthy controls. The uptake of an NMDAR selective ligand, [18F]GE179, was measured using positron emission tomography (PET) and indexed using the distribution volume ratio (DVR) and volume of distribution (VT, in millilitres per cubic centimetre) of [18F]GE179 in the hippocampus and additional exploratory regions (anterior cingulate cortex (ACC), thalamus, striatum and temporal lobe). Symptom severity was measured using the Positive and Negative Syndrome Scale (PANSS).

A total of 37 individuals were included in the analyses (mean [SD] age of controls, 26.7 [4.5] years; mean [SD] age of patients, 25.3 [4.9] years). There was a significant reduction in hippocampal DVR in the patients with schizophrenia relative to healthy controls (p = 0.02, Cohen's d = 0.81). Although the VT of [18F]GE179 was lower in absolute terms in patients, there was no significant effect of group on VT in the hippocampus (p = 0.15, Cohen's d = 0.49) or the exploratory brain regions. There was a negative association between hippocampal DVR and total PANSS symptoms (rho = –0.47, p = 0.04), depressive symptoms (rho = –0.67, p = 0.002), and general PANSS symptoms (rho = –0.74, p = 0.001).

These results indicate lower hippocampal NMDAR levels in schizophrenia relative to controls with a large effect size, and that lower NMDAR levels are associated with greater levels of symptom severity. These findings are consistent with the role of NMDAR hypofunction in the pathophysiology of schizophrenia; however, further work is required to test specificity and causal relationships.

Schizophrenia is notoriously becoming one of the world's most debilitating mental disorders, affecting 1 in 100 people. There is increasing evidence that neuroinflammation plays a part in the pathogenesis of schizophrenia and other psychotic disorders; microglial activity acting as a marker for neuroinflammatory reactions in the brain. Furthermore, cannabis is an illicit substance that also evokes a similar response in the neuroimmune activity. This project explores how cannabis exposure influences an elevation in neuroinflammatory responses through TSPO levels, and whether this information can help us determine if cannabis use and increased TSPO levels can be associated with a risk factor for developing psychosis.

55 participants (36 males and 19 females) were recruited from the community by the IRIS (Inflammatory Reaction in Schizophrenia) team at the IoPPN, King's College London, from which 34 patients with a diagnosis of schizophrenia and 21 healthy controls took part in the study. The eligible participants underwent clinical assessments and PET scanning, from which cannabis use history and PET data were collected. Participant neuroinflammatory levels are represented by [18F]DPA-714 volume and different regions of grey matter in the brain were analysed through multivariate analyses, the confounding variables being age and TSPO genotype.

A statistically significant association is shown between participants who have had exposure to cannabis and participants who have not had any exposure in their lifetime. The differences across the prioritised brain regions of interest were robust, the association appearing more apparent and statistically significant in the total (p = .00) and temporal grey matter (p = .00) regions of the brain. This may suggest that cannabis exposure influences the [18F]DPA-714 VT in the significant regions of interest. However, a negative association is seen with current use, the quantity of use, and the frequency of use.

The initial findings for cannabis exposure show us a positive association with increased TSPO levels, however, limitations must be taken into account. Although we cannot readily establish that elevated TSPO levels in cannabis users can presently act as a risk factor marker for developing psychosis from this particular study, we can utilise this data to continue our research in disclosing a new system to predict the occurrence of psychosis.

To conduct a meta-analysis of the effect of ketamine on psychopathology in healthy volunteers and patients with schizophrenia, and the experimental factors affecting this.

Ketamine is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like symptoms. Despite this, the consistency and magnitude of symptoms induced by ketamine, or what factors influence the effects of ketamine on these remain unknown.

MEDLINE, EMBASE and PsychINFO databases were searched for within-subject placebo controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or people with schizophrenia. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive and negative BPRS and PANSS scores were extracted. Sub-group analyses were conducted examining the effect of: blinding status, ketamine preparation, infusion method and time between ketamine and placebo condition. Standardized mean change scores were used as effect sizes for individual studies. Standardized mean changes between ketamine and placebo for total, positive and negative BPRS and PANSS were calculated.

Of 7819 citations retrieved, 36 studies involving healthy participants were included. The overall sample included 725 healthy volunteers exposed to both the ketamine and placebo condition. Ketamine induced a significant increase in transient psychopathology in healthy participants, for total (Standardized mean change (SMC) = 1.50 (95% CI = 1.23 to 1.77), p < 0.0001), positive (SMC = 1.55 (95% CI = 1.29 to 1.81), p < 0.0001) and negative (SMC = 1.16, (95% CI = 0.96 to 1.35), p < 0.0001) symptom ratings, relative to the placebo condition. This effect was significantly greater for positive symptoms than negative symptoms (p = 0.004). Bolus followed by constant infusion increased ketamine's effect on positive symptoms relative to infusion alone (p = 0.006). Single-day study design increased ketamine's effect on total symptoms (p = 0.007), but age and gender did not moderate effects. There were insufficient studies for meta-analysis of studies in schizophrenia. Of these studies, two found a significant increase in symptoms with ketamine administration in total and positive symptoms. Only one study found an increase in negative symptom severity with ketamine.

These findings show that acute ketamine administration induces schizophrenia-like symptomatology with large effect sizes but there is a greater increase in positive than negative symptoms, and when a bolus is used. These findings suggest bolus doses should be avoided in its therapeutic use to minimize the risk of inducing transient positive psychotic symptoms.

The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.

We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.

The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Psychosis, and in particular auditory verbal hallucinations (AVHs), are associated with adversity exposure. However, AVHs also occur in populations with no need for care or distress.

This study investigated whether adversity exposure would differentiate clinical and healthy voice-hearers within the context of a ‘three-hit’ model of vulnerability and stress exposure.

Samples of 57 clinical and 45 healthy voice-hearers were compared on the three ‘hits’: familial risk; adversity exposure in childhood and in adolescence/adulthood.

Clinical voice-hearers showed greater familial risk than healthy voice-hearers, with more family members with a history of psychosis, but not with other mental disorders. The two groups did not differ in their exposure to adversity in childhood [sexual and non-sexual, victimisation; discrimination and socio-economic status (SES)]. Contrary to expectations, clinical voice-hearers did not differ from healthy voice-hearers in their exposure to victimisation (sexual/non-sexual) and discrimination in adolescence/adulthood, but reported more cannabis and substance misuse, and lower SES.

The current study found no evidence that clinical and healthy voice-hearers differ in lifetime victimisation exposure, suggesting victimisation may be linked to the emergence of AVHs generally, rather than need-for-care. Familial risk, substance misuse and lower SES may be additional risk factors involved in the emergence of need-for-care and distress.

Heart disease is the leading cause of death in schizophrenia. However, there has been little research directly examining cardiac function in schizophrenia.

To investigate cardiac structure and function in individuals with schizophrenia using cardiac magnetic resonance imaging (CMR) after excluding medical and metabolic comorbidity.

In total, 80 participants underwent CMR to determine biventricular volumes and function and measures of blood pressure, physical activity and glycated haemoglobin levels. Individuals with schizophrenia (‘patients’) and controls were matched for age, gender, ethnicity and body surface area.

Patients had significantly smaller indexed left ventricular (LV) end-diastolic volume (effect size d = −0.82, P = 0.001), LV end-systolic volume (d = −0.58, P = 0.02), LV stroke volume (d = −0.85, P = 0.001), right ventricular (RV) end-diastolic volume (d = −0.79, P = 0.002), RV end-systolic volume (d = −0.58, P = 0.02), and RV stroke volume (d = −0.87, P = 0.001) but unaltered ejection fractions relative to controls. LV concentricity (d = 0.73, P = 0.003) and septal thickness (d = 1.13, P < 0.001) were significantly larger in the patients. Mean concentricity in patients was above the reference range. The findings were largely unchanged after adjusting for smoking and/or exercise levels and were independent of medication dose and duration.

Individuals with schizophrenia show evidence of concentric cardiac remodelling compared with healthy controls of a similar age, gender, ethnicity, body surface area and blood pressure, and independent of smoking and activity levels. This could be contributing to the excess cardiovascular mortality observed in schizophrenia. Future studies should investigate the contribution of antipsychotic medication to these changes.

Psychotic disorders are associated with metabolic abnormalities including alterations in glucose and lipid metabolism. A major challenge in the treatment of psychosis is to identify patients with vulnerable metabolic profiles who may be at risk of developing cardiometabolic co-morbidities. It is established that both central and peripheral metabolic organs use lipids to control energy balance and regulate peripheral insulin sensitivity. The endocannabinoid system, implicated in the regulation of glucose and lipid metabolism, has been shown to be dysregulated in psychosis. It is currently unclear how these endocannabinoid abnormalities relate to metabolic changes in psychosis. Here we review recent research in the field of metabolic co-morbidities in psychotic disorders as well as the methods to study them and potential links to the endocannabinoid system. We also describe the bioinformatics platforms developed in the EU project METSY for the investigations of the biological etiology in patients at risk of psychosis and in first episode psychosis patients. The METSY project was established with the aim to identify and evaluate multi-modal peripheral and neuroimaging markers that may be able to predict the onset and prognosis of psychiatric and metabolic symptoms in patients at risk of developing psychosis and first episode psychosis patients. Given the intrinsic complexity and widespread role of lipid metabolism, a systems biology approach which combines molecular, structural and functional neuroimaging methods with detailed metabolic characterisation and multi-variate network analysis is essential in order to identify how lipid dysregulation may contribute to psychotic disorders. A decision support system, integrating clinical, neuropsychological and neuroimaging data, was also developed in order to aid clinical decision making in psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic understanding of psychotic and metabolic disorders, facilitate early disease detection, aid treatment selection and elucidate new targets for pharmacological treatments.

The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.

We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.

This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.

Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).

Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.

Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans.

No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.

The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.

Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls.

Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage.

In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = −0.22; p = 0.29).

In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.

Ethnic minority individuals have an increased risk of developing a psychotic disorder, particularly if they live in areas of ethnic segregation, or low own group ethnic density. The neurobiological mechanisms underlying this ethnic minority associated risk are unknown. We used functional MRI to investigate neural responses to faces of different ethnicity, in individuals of black ethnicity, and a control group of white British ethnicity individuals.

In total 20 individuals of black ethnicity, and 22 individuals of white British ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Own group ethnic density was calculated from the 2011 census. Neighbourhood segregation was quantified using the Index of Dissimilarity method.

At the within-group level, both groups showed greater right amygdala activation to outgroup faces. Between groups, the black ethnicity group showed greater right amygdala activation to white faces, compared to the white ethnicity group. Within the black ethnicity group, individuals living in areas of lower own group ethnic density showed greater right amygdala reactivity to white faces (r = −0.61, p = 0.01).

This is the first time an increased amygdala response to white faces has been demonstrated in individuals of black ethnicity. In the black ethnicity group, correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. These results may have relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals.

The extent of metabolic and lipid changes in first-episode psychosis (FEP) is unclear.

To investigate whether individuals with FEP and no or minimal antipsychotic exposure show lipid and adipocytokine abnormalities compared with healthy controls.

We conducted a meta-analysis of studies examining lipid and adipocytokine parameters in individuals with FEP and no or minimal antipsychotic exposure v. a healthy control group. Studies reported fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and leptin levels.

Of 2070 citations retrieved, 20 case–control studies met inclusion criteria including 1167 patients and 1184 controls. Total cholesterol and LDL cholesterol levels were significantly decreased in patients v. controls, corresponding to an absolute reduction of 0.26mmol/L and 0.15mmol/L respectively. Triglyceride levels were significantly increased in the patient group, corresponding to an absolute increase of 0.08 mmol/L However, HDL cholesterol and leptin levels were not altered in patients v. controls.

Total and LDL cholesterol levels are reduced in FEP, indicating that hypercholesterolaemia in patients with chronic disorder is secondary and potentially modifiable. In contrast, triglycerides are elevated in FEP. Hypertriglyceridaemia is a feature of type 2 diabetes mellitus, therefore this finding adds to the evidence for glucose dysregulation in this cohort. These findings support early intervention targeting nutrition, physical activity and appropriate antipsychotic prescription.

It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population.

To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis.

We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode.

The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment.

Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes.