Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.

Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.

The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remission in first-episode psychosis.

Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 to 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 to 2009 from a further 11 English early intervention services. The one-year non-remission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for non-remission, which was externally validated.

The prediction model showed good discrimination (C-statistic of 0.74 (0.72, 0.76) and adequate calibration with intercept alpha of 0.13 (0.03, 0.23) and slope beta of 0.99 (0.87, 1.12). Our model improved the net-benefit by 16% at a risk threshold of 50%, equivalent to 16 more detected non-remitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases.

Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of non-remission at initial clinical contact.

Increasing evidence suggests psychosis may be more meaningfully viewed in dimensional terms rather than as discrete categorical states and that specific symptom clusters may be identified. If so, particular risk factors and premorbid factors may predict these symptom clusters.

(i) To explore, using principal component analysis, whether specific factors for psychotic symptoms can be isolated. (ii) To establish the predictors of the different symptom factors using multiple regression techniques.

One hundred and eighty-nine inpatients with psychotic illness were recruited and information on family history, premorbid factors and current symptoms obtained from them and their mothers.

Seven distinct symptom components were identified. Regression analysis failed to identify any developmental predictors of depression or mania. Delusions/hallucinations were predicted by a family history of schizophrenia and by poor school functioning in spite of normal premorbid IQ (F = 6.5; P < 0.001); negative symptoms by early onset of illness, developmental delay and a family history of psychosis (F = 4.1; P = 0.04). Interestingly disorganisation was predicted by the combination of family history of bipolar disorder and low premorbid IQ (F = 4.9; P = 0.003), and paranoia by obstetric complications (OCs) and poor school functioning (F = 4.2; P = 0.01).

Delusions and hallucinations, negative symptoms and paranoia all appeared to have a developmental origin though they were associated with different childhood problems. On the other hand, neither mania nor depression was associated with childhood dysfunction. Our most striking finding was that disorganisation appeared to arise when a familial predisposition to mania was compounded by low premorbid IQ.

To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis.

We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points.

Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up.

The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results.

It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.

Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23–0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power differential (between voice and voice hearer) was the mediator of the treatment effect.

The trial sample (n = 197) was used. A logistic regression model predicting 18-month compliance was used to identify predictors, and an exploratory principal component analysis (PCA) of baseline variables used as potential predictors (confounders) in their own right. Stata's paramed command used to obtain estimates of the direct, indirect and total effects of treatment.

Voice omnipotence was the best predictor although the PCA identified a highly predictive cognitive-affective dimension comprising: voices’ power, childhood trauma, depression and self-harm. In the mediation analysis, the indirect effect of treatment was fully explained by its effect on the hypothesised mediator: voice power differential.

Voice power and treatment allocation were the best predictors of harmful compliance up to 18 months; post-treatment, voice power differential measured at nine months was the mediator of the effect of treatment on compliance at 18 months.

It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations.

To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence.

Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study).

Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA.

A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed.

To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway.

Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed.

A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP.

Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.

None.

Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence.

To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs.

We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points.

At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS.

The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.

The nosological status of auditory hallucinations in non-clinical samples is unclear

To investigate the functional neural basis of non-clinical hallucinations

After selection from 1206 people, 68 participants of high, medium and low hallucination proneness completed a task designed to elicit verbal hallucinatory phenomena under conditions of stimulus degradation. Eight subjects who reported hearing a voice when none was present repeated the task during functional imaging

During the signal detection task, the high hallucination-prone participants reported a voice to be present when it was not (false alarms) significantly more often than the average or low participants (P<0.03, d.f. =2). On functional magnetic resonance imaging, patterns of activation during these false alarms showed activation in the superior and middle temporal cortex (P<0.001)

Auditory hallucinatory experiences reported in non-clinical samples appear to be mediated by similar patterns of cerebral activation as found during hallucinations in schizophrenia

There are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life.

To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia.

Cost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice.

Conventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective.

The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.