Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.

Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.

We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.

Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Difficulty in cognitive adjustment after a conflict or error is a hallmark for many psychiatric disorders, yet the underlying neural correlates are not fully understood. We have previously shown that post-success and post-error cognitive controls are associated with distinct mechanisms particularly related to the prefrontal-cerebellar circuit, raising the possibility that altered dynamic interactions in this circuit may underlie mental illness.

This study included 136 patients with three diagnosed disorders [48 schizophrenia (SZ), 49 bipolar disorder (BD), 39 attention deficit hyperactivity disorder (ADHD)] and 89 healthy controls who completed a stop-signal task during fMRI scans. Brain activations for concurrent, post-success, and post-error cognitive controls were analyzed and compared between groups. Dynamic causal modeling was applied to investigate prefrontal-cerebellar effective connectivity patterns during post-success and post-error processing.

No significant group differences were observed for brain activations and overall effective connectivity structures during post-success and post-error conditions. However, significant group differences were shown for the modulational effect on top-down connectivity from the prefrontal cortex to the cerebellum during post-error trials (pFWE = 0.02), which was driven by reduced modulations in both SZ and ADHD. During post-success trials, there were significantly decreased modulational effect on bottom-up connectivity from the cerebellum to the prefrontal cortex in ADHD (pFWE = 0.04) and decreased driving input to the cerebellum in SZ (pFWE = 0.04).

These findings suggest that patients with SZ and ADHD are associated with insufficient neural modulation on the prefrontal-cerebellar circuit during post-success and post-error cognitive processing, a phenomenon that may underlie cognitive deficits in these disorders.

There is increasing evidence that assessing outcomes in terms of capability provides information beyond that of health-related quality of life (HRQoL) for outcome evaluation in mental health research and clinical practice.

To assess similarities and differences in the measurement properties of the ICECAP-A capability measure and Oxford Capabilities Questionnaire for Mental Health (OxCAP-MH) in people with schizophrenia experiencing depression, and compare these measurement properties with those of (a) the EuroQol EQ-5D-5L and EuroQol Visual Analogue Scale (EQ-VAS) and (b) mental health-specific (disease-specific) measures.

Using data for 100 patients from the UK, measurement properties were compared using correlation analyses, Bland–Altman plots and exploratory factor analysis. Responsiveness was assessed by defining groups who worsened, improved or remained unchanged, based on whether there was a clinically meaningful change in the instrument scores between baseline and 9-month follow-up assessments.

The two capability instruments had stronger convergent validity with each other (Spearman's rho = 0.677) than with the HRQoL (rho = 0.354–0.431) or the mental health-specific (rho = 0.481–0.718) instruments. The OxCAP-MH tended to have stronger correlations with mental health-specific instruments than the ICECAP-A, whereas the ICECAP-A had slightly stronger correlation with the EQ-VAS. Change scores on the capability instruments correlated weakly with change scores on the HRQoL scales (rho = 0.131–0.269), but moderately with those on mental health-specific instruments for the ICECAP-A (rho = 0.355–0.451) and moderately/strongly on the OxCAP-MH (rho = 0.437–0.557).

Assessing outcomes in terms of capabilities for people with schizophrenia and depression provided more relevant, mental health-specific information than the EQ-5D-5L or the EQ-VAS. The ICECAP-A and the OxCAP-MH demonstrated similar psychometric properties, but the OxCAP-MH was more correlated with disease-specific instruments.

The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable.

Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages.

Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex.

Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.

People with severe mental illness (SMI) are more likely to have obesity and engage in health risk behaviours than the general population. The aims of this study are (1) evaluate the effectiveness of interventions that focus on body weight, smoking cessation, improving sleeping patterns, and alcohol and illicit substance abuse; (2) Compare the number of interventions addressing body weight and health risk behaviours in low- and middle-income countries (LMICs) v. those reported in published systematic reviews focusing on high-income countries (HICs).

Intervention studies published up to December 2020 were identified through a structured search in the following database; OVID MEDLINE (1946–December 2020), EMBASE (1974–December 2020), CINAHL (1975–2020), APA PsychoINFO (1806–2020). Two authors independently selected studies, extracted study characteristics and data and assessed the risk of bias. and risk of bias was assessed using the Cochrane risk of bias tool V2. We conducted a narrative synthesis and, in the studies evaluating the effectiveness of interventions to address body weight, we conducted random-effects meta-analysis of mean differences in weight gain. We did a systematic search of systematic reviews looking at cardiometabolic and health risk behaviours in people with SMI. We compared the number of available studies of LMICs with those of HICs.

We assessed 15 657 records, of which 9 met the study inclusion criteria. Six focused on healthy weight management, one on sleeping patterns and two tested a physical activity intervention to improve quality of life. Interventions to reduce weight in people with SMI are effective, with a pooled mean difference of −4.2 kg (95% CI −6.25 to −2.18, 9 studies, 459 participants, I2 = 37.8%). The quality and sample size of the studies was not optimal, most were small studies, with inadequate power to evaluate the primary outcome. Only two were assessed as high quality (i.e. scored ‘low’ in the overall risk of bias assessment). We found 5 reviews assessing the effectiveness of interventions to reduce weight, perform physical activity and address smoking in people with SMI. From the five systematic reviews, we identified 84 unique studies, of which only 6 were performed in LMICs.

Pharmacological and activity-based interventions are effective to maintain and reduce body weight in people with SMI. There was a very limited number of interventions addressing sleep and physical activity and no interventions addressing smoking, alcohol or harmful drug use. There is a need to test the feasibility and cost-effectiveness of context-appropriate interventions to address health risk behaviours that might help reduce the mortality gap in people with SMI in LMICs.

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.

Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.

Baseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.

Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.

The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.

Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder.

The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status.

Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001).

Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.

The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning.

A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15–28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA.

We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning.

Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Despite a large descriptive literature linking creativity and risk for psychiatric illness, the magnitude and specificity of this relationship remain controversial.

We examined, in 1 137 354 native Swedes with one of 59 3-digit official and objective occupational codes in managerial and educated classes, their familial genetic risk score (FGRS) for ten major disorders, calculated from 1st through 5th degree relatives. Mean FGRS across disorders were calculated, in 3- and 4-digit occupational groups, and then controlled for those whose disorder onset preceded occupational choice. Using sequential analyses, p values were evaluated using Bonferroni correction.

3-digit professions considered to reflect creativity (e.g. ‘artists’ and ‘authors’) were among those with statistically significant elevations of FGRS. Among more specific 4-digit codes, visual artists, actors, and authors stood out with elevated genetic risks, highest for major depression (MD), anxiety disorders (AD) and OCD, more modest for bipolar disorders (BD) and schizophrenia and, for authors, for drug and alcohol use disorders. However, equal or greater elevations in FGRS across disorders were seen for religious (e.g. ministers), helping (e.g. psychologists, social workers), and teaching/academic occupations (e.g. professors). The potential pathway from FGRS → Disorder → Occupation accounts for a modest proportion of the signal, largely for MD and AD risk.

While traditional creative occupations were associated with elevated genetic risk for a range of psychiatric disorders, this association was not unique, as similar, or greater elevations were seen for religious, helping and teaching professions and was stronger for internalizing than psychotic disorders.

Cognitive impairment is common in people with mental disorders, leading to transdiagnostic classification based on cognitive characteristics. However, few studies have used this approach for intellectual abilities and functional outcomes.

The present study aimed to classify people with mental disorders based on intellectual abilities and functional outcomes in a data-driven manner.

Seven hundred and forty-nine patients diagnosed with schizophrenia, bipolar disorder, major depression disorder or autism spectrum disorder and 1030 healthy control subjects were recruited from facilities in various regions of Japan. Two independent k-means cluster analyses were performed. First, intelligence variables (current estimated IQ, premorbid IQ, and IQ discrepancy) were included. Second, number of work hours per week was included instead of premorbid IQ.

Four clusters were identified in the two analyses. These clusters were specifically characterised in terms of IQ discrepancy in the first cluster analysis, whereas the work variable was the most salient feature in the second cluster analysis. Distributions of clinical diagnoses in the two cluster analyses showed that all diagnoses were unevenly represented across the clusters.

Intellectual abilities and work outcomes are effective classifiers in transdiagnostic approaches. The results of our study also suggest the importance of diagnosis-specific strategies to support functional recovery in people with mental disorders.

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.

The Global Burden of Disease attributable to psychotic disorders in African countries is high and has increased sharply in recent years. Yet, there is a scarcity of evidence on effective, appropriate and acceptable interventions for schizophrenia and other psychotic disorders on the continent.

We carried out a systematic review and narrative synthesis of peer-reviewed literature evaluating the impact of non-pharmacological interventions for adolescents and adults (10–65 years) in African countries. Two reviewers independently double-screened all articles and performed data extraction and quality appraisal using standardized tools.

Of the 8529 unique texts returned by our search, 12 studies were identified for inclusion, from seven countries: Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Sudan. They evaluated a range of interventions with one or more clinical, psychological or psychosocial, education or awareness or traditional or faith-based components, and were delivered by either mental health specialists or non-specialist health workers. Ten of the 12 included studies reported significant, positive effects on a range of outcomes (including functioning, symptoms and stigma). Nearly half of the interventions were based out of health facilities. Based on quality appraisals, confidence in these studies' findings is only rated low to medium.

Further research is needed to develop and evaluate interventions that meet the diverse needs of people with psychosis, within and beyond the health sector.

To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with yoga training (YT) for persons with schizophrenia (SZ).

The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single-blind randomised controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomised to receive treatment as usual (TAU), TAU augmented with YT or TAU augmented with meditation and yoga training (MYT) for 3 weeks (N = 145). Acceptability, clinical, social and cognitive functions were assessed after 3-week and 3-month post-randomisation using within-group and between-group analyses with repeated measures multivariate tests.

No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range.

MYT is feasible and acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.