Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation.

To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions.

We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs).

Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins.

These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge.

The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge.

The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = −4.58, 95% CI −9.03 to −0.13, p = 0.044) in the intervention condition compared to control.

These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.

Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.

The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.

We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.

We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.

In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.

Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.

To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:

1. 1. determine the extent to which this is altered in schizophrenia and

2. 2. use a verbal fluency paradigm.

1. 1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and

2. 2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.

Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.

The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.

Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.

The heritability of the brain’s structure and function in schizophrenia remains elusive

To assess the influence of genetic and environmental factors on executive function in schizophrenia.

A twin-sibling study of 206 subjects; 163 twins, varying in their zygosity and concordance for schizophrenia, and 43 singletons from sibling clusters varying in their concordance for schizophrenia. We assessed performance and regional brain activation using functional magnetic resonance imaging, during a phonological verbal fluency task.

Patients and their unaffected relatives developed greater activation in the left inferior frontal gyrus, and greater deactivation in the middle temporal gyri bilaterally. These features were maximally evident in subjects with schizophrenia. When the analysis was restricted to the unaffected relatives and healthy controls, a similar pattern was evident. Heritability was greatest in the left hippocampus and the right middle temporal gyrus. Genetic modelling indicated a phenotypic correlation between schizophrenia and increased activity in the inferior frontal gyrus and reduced activity in the left middle temporal gyrus and left hippocampus, which appeared principally due to shared genetic effects.

Both schizophrenia and its familial vulnerability were associated with altered frontal, parahippocampal and temporal activation during verbal fluency. The altered left inferior frontal activity was particularly associated with schizophrenia, while altered left medial temporal and right middle temporal activity were more heritable. The latter was more intimately linked to the genetic risk for schizophrenia, and thus the better candidate intermediate phenotype.

To evaluate the initial (3 months) all-cause discontinuation and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, stratified by previous treatment.

These two studies (NCT00705783 & NCT00706654) were double-blind, placebo- or active-controlled assessing the efficacy and safety of AOM-400mg. Detailed study designs have been reported previously (1, 2). This analysis was conducted on the pooled population in the first 3 months after initiating AOM-400mg treatment, on patients who received at least one dose of AOM-400mg. Outcome measures are reported for groups stratified by prior treatment.

During the first 3 months of treatment, discontinuation due to all-causes (except for those who discontinued due to the sponsor stopping the NCT00705783 study early after pre-specified efficacy parameters were met) as well as due to adverse events are presented in Table 1. The rates of insomnia and akathisia are shown in Table 1

Aripiprazole once-monthly 400mg appeared equally safe and effective (as measured by all cause discontinuation) in the first 3 months after initiation, regardless of treatment prior to entering trials.