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Background: Schizophrenia is a brain dysconnectivity disorder. However, it is not well understood whether the experience of childhood trauma (CT) affects dysconnectivity in individuals with schizophrenia (SZ). Using a network-based approach, we examined whether self-reported CT would explain additional variance compared to whole-brain topology and structural connectivity changes in SZ versus healthy controls (HC)., Material and Methods: CT was assessed in 51 SZ (mean age ± standard deviation 44 ± 11 years) and 140 HC (34.0 ± 12 years). Structural brain networks were constructed from T1-weighted MR and diffusion-MRI scans using non-tensor based tractography. Group differences in whole-brain topology and permutation-based statistics were examined and corrected for age and sex., Results: SZ showed reductions in efficiency, strength, clustering and density (p < 0.01) as well as increases in path length (F (range)  = 4.71-18.1, p < 0.03) when compared to HC. We also observed hypoconnectivity in a subnetwork of frontotemporal, frontoparietal and occipital regions in SZ relative to HC (T > 4.0, p < 0.001). However, we did not find that high CT levels were related to structural network differences or structural connectivity changes in SZ., Conclusions: CT did not impact on topology or subnetwork connectivity changes in SZ. High CT levels were also not associated with any differences in network organisation irrespective of diagnosis. However, our findings confirm that SZ showed both network-level reductions and increases in a subnetwork. These findings suggest that the patterns of neuroanatomical dysconnectivity in established schizophrenia may not be influenced by CT. Future studies are needed to investigate the association between CT and structural dysconnectivity in schizophrenia., Competing Interests: Declaration of competing interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Myocyte Enhancer Factor 2C (MEF2C) is a transcription factor that plays a crucial role in neurogenesis and synapse development. Genetic studies have identified MEF2C as a gene that influences cognition and risk for neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ). Here, we investigated the involvement of MEF2C in these phenotypes using human-derived neural stem cells (NSCs) and glutamatergic induced neurons (iNs), which represented early and late neurodevelopmental stages. For these cellular models, MEF2C function had previously been disrupted, either by direct or indirect mutation, and gene expression assayed using RNA-seq. We integrated these RNA-seq data with MEF2C ChIP-seq data to identify dysregulated direct target genes of MEF2C in the NSCs and iNs models. Several MEF2C direct target gene-sets were enriched for SNP-based heritability for intelligence, educational attainment and SCZ, as well as being enriched for genes containing rare de novo mutations reported in ASD and/or developmental disorders. These gene-sets are enriched in both excitatory and inhibitory neurons in the prenatal and adult brain and are involved in a wide range of biological processes including neuron generation, differentiation and development, as well as mitochondrial function and energy production. We observed a trans expression quantitative trait locus (eQTL) effect of a single SNP at MEF2C (rs6893807, which is associated with IQ) on the expression of a target gene, BNIP3L. BNIP3L is a prioritized risk gene from the largest genome-wide association study of SCZ and has a function in mitophagy in mitochondria. Overall, our analysis reveals that either direct or indirect disruption of MEF2C dysregulates sets of genes that contain multiple alleles associated with SCZ risk and cognitive function and implicates neuron development and mitochondrial function in the etiology of these phenotypes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Exposure to early life adversity is associated with both increased risk of developing schizophrenia and poorer performance on measures of social cognitive functioning. In this study, we examined whether interleukin-6 (IL-6) and Corpus Callosum (CC) microstructure mediated the association between childhood physical neglect and social cognition. Fifty-eight patients with a diagnosis of schizophrenia were included. The CANTAB emotion recognition task (unbiased hit rate) was used to assess social cognition. We found that the microstructural organization of the CC significantly mediated the association between physical neglect and emotion recognition. Furthermore, in a sequential mediation analysis that also considered the role of inflammatory response, the association between physical neglect, and lower emotion recognition performance was sequentially mediated by higher IL-6 and lower fractional anisotropy of the CC. This mediating effect of IL-6 was only present when simultaneously considering the effects of CC microstructural organization and remained significant while controlling for the effects of sex, BMI and medication dosage (but not age). Overall, the findings suggest that the association between physical neglect and poorer emotion recognition in schizophrenia occurs, at least in part, via its association with white matter microstructure., Competing Interests: Declaration of Competing Interest All authors confirm that they have no conflict of interest in relation to this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Recent studies have reported a negative association between exposure to childhood trauma, including physical neglect, and cognitive functioning in patients with schizophrenia. Childhood trauma has been found to influence immune functioning, which may contribute to the risk of schizophrenia and cognitive symptoms of the disorder. In this study, we aimed to test the hypothesis that physical neglect is associated with cognitive ability, and that this association is mediated by a combined latent measure of inflammatory response, and moderated by higher genetic risk for schizophrenia. The study included 279 Irish participants, comprising 102 patients and 177 healthy participants. Structural equation modelling was used to perform mediation and moderation analyses. Inflammatory response was measured via basal plasma levels of IL-6, TNF-α, and CRP, and cognitive performance was assessed across three domains: full-scale IQ, logical memory, and the emotion recognition task. Genetic variation for schizophrenia was estimated using a genome-wide polygenic score based on genome-wide association study summary statistics. The results showed that inflammatory response mediated the association between physical neglect and all measures of cognitive functioning, and explained considerably more variance than any of the inflammatory markers alone. Furthermore, genetic risk for schizophrenia was observed to moderate the direct pathway between physical neglect and measures of non-social cognitive functioning in both patient and healthy participants. However, genetic risk did not moderate the mediated pathway associated with inflammatory response. Therefore, we conclude that the mediating role of inflammatory response and the moderating role of higher genetic risk may independently influence the association between adverse early life experiences and cognitive function in patients and healthy participants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The Corona Radiata (CR) is a large white matter tract in the brain comprising of the anterior CR (aCR), superior CR (sCR), and posterior CR (pCR), which have associations with cognition, self-regulation, and, in schizophrenia, positive symptom severity. This study tested the hypothesis that the microstructural organisation of the aCR, as measured by Fractional Anisotropy (FA) using Diffusion Tensor Imaging (DTI), would relate to poorer social cognitive outcomes and higher positive symptom severity for people with schizophrenia, when compared to healthy participants. We further hypothesised that increased positive symptoms would relate to poorer social cognitive outcomes., Methods: Data were derived from n = 178 healthy participants (41 % females; 36.11 ± 12.36 years) and 58 people with schizophrenia (30 % females; 42.4 ± 11.1 years). The Positive and Negative Symptom Severity Scale measured clinical symptom severity. Social Cognition was measured using the Reading the Mind in the Eyes Test (RMET) Total Score, as well as the Positive, Neutral, and Negative stimuli valence. The ENIGMA-DTI protocol tract-based spatial statistics (TBSS) was used., Results: There was a significant difference in FA for the CR, in individuals with schizophrenia compared to healthy participants. On stratification, both the aCR and pCR were significantly different between groups, with patients showing reduced white matter tract microstructural organisation. Significant negative correlations were observed between positive symptomatology and reduced microstructural organisation of the aCR. Performance for RMET negative valence items was significantly correlated bilaterally with the aCR, but not the sCR or pCR, and no relationship to positive symptoms was observed., Conclusions: These data highlight specific and significant microstructural white-matter differences for people with schizophrenia, which relates to positive clinical symptomology and poorer performance on social cognition stimuli. While reduced FA is associated with higher positive symptomatology in schizophrenia, this study shows the specific associated with anterior frontal white matter tracts and reduced social cognitive performance. The aCR may have a specific role to play in frontal-disconnection syndromes, psychosis, and social cognitive profile within schizophrenia, though further research requires more sensitive, specific, and detailed consideration of social cognition outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Childhood trauma (CT) is associated with lower cognitive and social cognitive function in schizophrenia. Recent evidence suggests that the relationship between CT and cognition is mediated by both low-grade systemic inflammation and reduced connectivity of the default mode network (DMN) during resting state. This study sought to test whether the same pattern of associations was observed for DMN connectivity during task based activity. Fifty-three individuals with schizophrenia (SZ) or schizoaffective disorder (SZA) and one hundred and seventy six healthy participants were recruited from the Immune Response and Social Cognition (iRELATE) project. A panel of pro-inflammatory markers that included IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNFa), and C-reactive protein (CRP), were measured in plasma using ELISA. DMN connectivity was measured during an fMRI social cognitive face processing task. Patients showed evidence of low grade systemic inflammation and significantly increased connectivity between the left lateral parietal (LLP) cortex-cerebellum and LLP-left angular gyrus compared to healthy participants. Across the entire sample, IL-6 predicted increased connectivity between LLP-cerebellum, LLP-precuneus, and mPFC-bilateral-precentral-gyri and left postcentral gyrus. In turn, and again in the entire sample, IL-6 (but no other inflammatory marker) mediated the relationship between childhood physical neglect and LLP-cerebellum. Physical neglect scores also significantly predicted the positive association between IL-6 and LLP-precuneus connectivity. This is to our knowledge the first study that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during task based activity. Consistent with our hypothesis, exposure to trauma is associated with weaker suppression of the DMN during a face processing task, and this association was mediated via increased inflammatory response. The findings may represent part of the biological mechanism by which CT and cognitive performance are related., (© 2023. The Author(s).)

It has been reported that childhood trauma (CT) is associated with reductions in fractional anisotropy (FA) in individuals with schizophrenia (SZ). Here, we hypothesized that SZ with high levels of CT will show the greatest reductions in FA in frontolimbic and frontoparietal regions compared to healthy controls (HC) with high trauma levels and participants with no/low levels of CT. Thirty-seven SZ and 129 HC with CT experience were dichotomized into groups of 'none/low' or 'high' levels. Participants underwent diffusion-weighted MRI, and Tract-based spatial statistics were employed to assess the main effect of diagnosis, main effect of CT severity irrespective of diagnosis, and interaction between diagnosis and CT severity. SZ showed FA reductions in the corpus callosum and corona radiata compared to HC. Irrespective of a diagnosis, high CT levels (n = 48) were related to FA reductions in frontolimbic and frontoparietal regions compared to those with none/low levels of CT (n = 118). However, no significant interaction between diagnosis and high levels of CT was found (n = 13). Across all participants, we observed effects of CT on late developing frontolimbic and frontoparietal regions, suggesting that the effects of CT severity on white matter organization may be independent of schizophrenia., Competing Interests: Declaration of Competing Interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Currently, there are limited data comparing demographic and clinical characteristics of individuals who died by probable suicide and who did and did not previously attend mental health services (MHSs). This study compared demographic and clinical factors for both groups, in a Western region of Ireland over a 13-year period. Postmortem reports between January 1, 2006 and March 31, 2019 were reviewed for 400 individuals who died by probable suicide. Relevant sociodemographic and clinical data were extracted from individuals' lifetime case notes. One hundred and fifty nine individuals (40%) had attended MHSs at some stage ("attendee"). Hanging was the most common method of suicide (61%), followed by drowning (18%) for both attendees and nonattendees of MHSs, with more violent methods utilized overall by nonattendees (p = 0.028). Sixty-eight percent of individuals who previously attempted hanging subsequently died utilizing this method. A higher proportion of attendees were female compared to nonattendees of MHSs (28.9 vs. 14.5%, p = 0.001). Recurrent depressive disorder (55%) was the most common diagnosed mental health disorder. For individuals with a diagnosis of schizophrenia, 39% had antipsychotic medications detectable in their toxicology reports. In conclusion, the majority of people who died by probable suicide had never had contact with MHSs, and nonattendees overall were more likely to utilize violent methods of suicide. Nonconcordance with psychotropic medications in psychotic patients and previous hanging attempt were highlighted as potential risk factors for death by probable suicide.

Background: Cognitive difficulties are experienced frequently in schizophrenia (SZ) and are strongly predictive of functional outcome. Although severity of cognitive difficulties has been robustly associated with early life adversity, whether and how they are affected by current stress is unknown. The present study investigated whether acute stress reactivity as measured by heart rate and mood changes predict cognitive performance in patients with schizophrenia and healthy individuals, and whether this is moderated by diagnosis and previous childhood trauma exposure., Methods: One hundred and four patients with schizophrenia and 207 healthy participants were administered a battery of tasks assessing cognitive performance after psychosocial stress induction (Trier Social Stress Test; TSST). Mood states (Profile of Mood States; POMS) and heart rate were assessed at baseline, immediately before, and after the TSST., Results: Both healthy participants and patients showed increases in POMS Tension and Total Mood Disturbance scores between Time Point 2 (pre-TSST) and Time Point 3 (post-TSST). These changes were not associated with variation in cognition. Although childhood trauma exposure was associated with higher stress reactivity and poorer cognitive function in all participants, childhood trauma did not moderate the association between stress reactivity and cognition. Neither was diagnosis a moderator of this relationship., Discussion: These findings suggest that while chronic stress exposure explains significant variation in cognition, acute stress reactivity (measured by changes in Tension and Total Mood Disturbance) did not. In the context of broader developmental processes, we conclude that stressful events that occur earlier in development, and with greater chronicity, are likely to be more strongly associated with cognitive variation than acute transient stressors experienced in adulthood., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Exposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity., Methods: Three-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity., Results: Higher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β indirect -0.0234, 95% CI: -0.0573 to -0.0074; CTQ physical neglect: β indirect  = -0.0316, 95% CI: -0.0741 to -0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β indirect  = -0.0618, 95% CI: -0.1523 to -0.285)., Conclusion: This work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6's association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated., Methods: CT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations., Results: Seed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM., Conclusions: These findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

This study investigates changes on white matter microstructure and neural networks after 6 months of switching to clozapine in schizophrenia patients compared to controls, and whether any changes are related to clinical variables. T1 and diffusion-weighted MRI images were acquired at baseline before commencing clozapine and after 6 months of treatment for 22 patients with treatment-resistant schizophrenia and 23 controls. The Tract-based spatial statistics approach was used to compare changes over time between groups in fractional anisotropy (FA). Changes in structural network organisation weighted by FA and number of streamlines were assessed using graph theory. Patients displayed a significant reduction of FA over time (p<0.05) compared to controls in the genu and body of the corpus callosum and bilaterally in the anterior and superior corona radiata. There was no correlation between FA change in patients and changes in clinical variables or serum level of clozapine. There was no changes in structural network organisation between groups (F(7,280)=2.80;p = 0.187). This longitudinal study demonstrated progressive focal FA abnormalities in key anterior tracts, but preserved brain structural network organisation in patients. The FA reduction was independent of any clinical measures and may reflect progression of the underlying pathophysiology of this malignant form of schizophrenia illness., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To examine the rate of monitoring of metabolic syndrome and actual rates of metabolic syndrome in two patient cohorts [clozapine treatment and long-acting injectable (LAI) antipsychotic] who are reviewed on an equally regular basis (1-4 weekly) for administration of treatment., Methods: Clinical and laboratory data are examined on 119 patients treated with clozapine and 116 patients treated with LAI antipsychotic medications to determine the rates of metabolic syndrome and evidence of monitoring for metabolic syndrome in the previous 6 months. Individuals with insufficient data from these cohorts were invited to attend for metabolic screening to determine actual rates of metabolic syndrome in these two cohorts of patients., Results: All metabolic parameters were monitored to a significantly greater extent in the clozapine cohort (>90%), compared to those treated with LAI antipsychotic medications (<50%) (blood pressure, weight, lipid and glucose levels; p < 0.001). Metabolic syndrome was present in 38.9% of those treated with clozapine compared to 31.1% of patients treated with LAI antipsychotic medications (X2 = 0.54, p = 0.46)., Conclusions: These findings suggest that a robust screening plan should be in place to monitor for metabolic syndrome in individuals treated with LAI antipsychotic medications. This screening should include measurement of body weight, waist circumference, fasting glucose, lipids and fasting insulin levels. Early recognition of abnormal metabolic parameters allows early intervention, therefore, improving long-term cardiovascular outcomes.

Objective: This study investigated associations between childhood trauma, parental bonding, and social cognition (i.e., Theory of Mind and emotion recognition) in patients with schizophrenia and healthy adults., Methods: Using cross-sectional data, we examined the recollections of childhood trauma experiences and social cognitive abilities in 74 patients with schizophrenia and 116 healthy adults., Results: Patients had significantly higher scores compared with healthy participants on childhood trauma, and lower scores on parental bonding and social cognitive measures. Physical neglect was found to be the strongest predictor of emotion recognition impairments in both groups. Optimal parental bonding attenuated the impact of childhood trauma on emotion recognition., Conclusion: The present study provides evidence of an association between physical neglect and emotion recognition in patients with schizophrenia and healthy individuals and shows that both childhood trauma and parental bonding may influence social cognitive development. Psychosocial interventions should be developed to prevent and mitigate the long-term effects of childhood adversities., (© 2020 Wiley Periodicals LLC.)

Background: Deficits in facial emotion recognition are a core feature of schizophrenia and predictive of functional outcome. Higher plasma levels of the cytokine interleukin 6 (IL-6) have recently been associated with poorer facial emotion recognition in individuals with schizophrenia and healthy participants, but the neural mechanisms affected remain poorly understood., Methods: Forty-nine individuals with schizophrenia or schizoaffective disorder and 158 healthy participants were imaged using functional magnetic resonance imaging during a dynamic facial emotion recognition task. Plasma IL-6 was measured from blood samples taken outside the scanner. Multiple regression was used in statistical parametric mapping software to test whether higher plasma IL-6 predicted increased neural response during task performance., Results: Higher plasma IL-6 predicted increased bilateral medial prefrontal response during neutral face processing compared to angry face processing in the total sample (N = 207, t max  = 5.67) and increased left insula response during angry face processing compared to neutral face processing (N = 207, t max  = 4.40) (p < 0.05, family-wise error corrected across the whole brain at the cluster level)., Conclusions: These findings suggest that higher peripheral IL-6 levels predict altered neural response within brain regions involved in social cognition and emotion during facial emotion recognition. This is consistent with recent neuroimaging research on IL-6 and suggesting a possible neural mechanism by which this cytokine might affect facial emotion recognition accuracy., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions-the amygdala, hippocampus and anterior cingulate cortex (ACC)-mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function., (© The Author(s) 2020. Published by Oxford University Press.)

The association of antipsychotic medication with abnormal brain morphometry in schizophrenia remains uncertain. This study investigated subcortical morphometric changes 6 months after switching treatment to clozapine in patients with treatment-resistant schizophrenia compared with healthy volunteers, and the relationships between longitudinal volume changes and clinical variables. In total, 1.5T MRI images were acquired at baseline before commencing clozapine and again after 6 months of treatment for 33 patients with treatment-resistant schizophrenia and 31 controls, and processed using the longitudinal pipeline of Freesurfer v.5.3.0. Two-way repeated MANCOVA was used to assess group differences in subcortical volumes over time and partial correlations to determine association with clinical variables. Whereas no significant subcortical volume differences were found between patients and controls at baseline (F(8,52) = 1.79; p = 0.101), there was a significant interaction between time, group and structure (F(7,143) = 52.54; p < 0.001). Corrected post-hoc analyses demonstrated that patients had significant enlargement of lateral ventricles (F(1,59) = 48.89; p < 0.001) and reduction of thalamus (F(1,59) = 34.85; p < 0.001), caudate (F(1,59) = 59.35; p < 0.001), putamen (F(1,59) = 87.20; p < 0.001) and hippocampus (F(1,59) = 14.49; p < 0.001) volumes. Thalamus and putamen volume reduction was associated with improvement in PANSS (r = 0.42; p = 0.021, r = 0.39; p = 0.033), SANS (r = 0.36; p = 0.049, r = 0.40; p = 0.027) and GAF (r = -0.39; p = 0.038, r = -0.42; p = 0.024) scores. Reduced thalamic volume over time was associated with increased serum clozapine level at follow-up (r = -0.44; p = 0.010). Patients with treatment-resistant schizophrenia display progressive subcortical volume deficits after switching to clozapine despite experiencing symptomatic improvement. Thalamo-striatal progressive volumetric deficit associated with symptomatic improvement after clozapine exposure may reflect an adaptive response related to improved outcome rather than a harmful process.

Purpose: Deinstitutionalisation in Ireland began following the impetus of the successful transfer of psychiatric patients into the community in other countries. This study sought to evaluate the quality of life (QoL) and social functioning (SF) of former long-stay institutionalised patients with severe and enduring mental illness who had been relocated into local community settings and followed up 10 years later., Method: One month prior to hospital closure, 87 former long-stay psychiatric patients, the majority of whom had a diagnosis of schizophrenia, were assessed on a range of QoL and SF measures. Patients were followed-up 10 years later in the community, to evaluate baseline predictors of quality of life and social functioning., Results: Study completers (n = 35) improved significantly on a range of QoL and SF measures over the 10 year period. Specific improvements were noted in domestic skills (t = - 2.8, p < 0.0008), community skills (t = - 4.9, p < 0.001), as well as the activity and social relations measure (t = - 4.1, p < 0.001). Increased social function (t = - 6.3, p < 0.001) and improvement on the social behaviour scale (t = 7.6, p < 0.001) were noted at follow-up. Linear regression analysis found that less social behaviour problems at baseline predicted QoL 10 years later (t = - 2.6, p < 0.02)., Conclusion: This study demonstrated that transfer into the community from an institutional environment was associated with long-term improvements in quality of life and social functioning, even in those who spent many years in the institution. Those who demonstrated the greatest improvement in QoL had less social behavioural problems at baseline assessment, providing further evidence of the success of community living for former long-stay patients.

Background: Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis., Methods: Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3-6 months post-treatment., Results: Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3-6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition., Conclusions: CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.

Treatment: non-adherence in patients with schizophrenia is the most common reason for a relapse of psychosis. In a cohort of participants in Pakistan who suffered a relapse of psychosis, we aimed to identify the principal factors associated with non-adherence, including any culture specific factors that might not be as significant in other jurisdictions. Semi-structured interviews were undertaken at four psychiatric hospitals in the Peshawar region in Pakistan with 55 participants (44 male and 11 female) diagnosed with schizophrenia, who had suffered a relapse of psychosis subsequent to treatment non-adherence. The five principal documented reasons for treatment non-adherence were: 1) alternative treatment pathway chosen with a traditional faith healers (n=53, 96.4%), 2) lack of insight (n=36, 65.5%), 3) poor economic status (n=33, 60.0%), 4) adverse effects of medications (n=33, 60.0%) and 5) utilising psycho-active substances as an alternative to psychotropic medications (n=27, 41.1%). A number of identified factors associated with a relapse of psychosis are potentially modifiable including the provision of a range of pharmacological options including second generation antipsychotic agents, long acting injectable antipsychotics and psycho-therapeutic interventions including psycho-education. These interventions should prove cost effective and be associated with reduced relapse rates of psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The objective of the study was to explore the experiences of individuals admitted to the hospital involuntarily under the Mental Health Act 2001 in the Republic of Ireland., Methods: In this qualitative descriptive study, 50 individuals who had been involuntarily admitted to a hospital underwent face-to-face semistructured interviews approximately three months after revocation of the involuntary admission order. Data were analyzed by using an inductive thematic process., Results: Participants reported mixed experiences over the course of the admission, with both positive and challenging aspects. Participants reported feeling coerced, disempowered, and unsupported at various stages of the admission and highlighted the long-term deleterious impact on their psychological well-being. However, participants also described encounters with individuals who endeavored to initiate a collaborative, informative, and compassionate approach. Four key themes emerged consistently across the trajectory of participants' involuntary admission experiences: feeling trapped and coerced, feeling disengaged and unsupported, admission-induced distress, and person-centered encounters., Conclusions: This qualitative study of service users' views across the entire trajectory of their involuntary admission identified a number of factors that should be addressed to reduce the negative impact of involuntary admission. A multifaceted strategy could include ongoing education and training of all stakeholders in the principles and practices of person-centered care, repeated provision of accessible information and emotional support to service users during all stages of involuntary admission, and a shift in culture to one that minimizes the traumatic impact of forced detention on individuals' psychological well-being.

Despite a large body of research evaluating factors associated with the relapse of psychosis in schizophrenia, no studies in Pakistan have been undertaken to date to identify any such factors, including specific cultural factors pertinent to Pakistan. Semistructured interviews and psychometric measures were undertaken with 60 patients diagnosed with schizophrenia (49 male and 11 female) and their caregivers at four psychiatric hospitals in the Peshawar region in Pakistan. Factors significantly associated with psychotic relapse included treatment non-adherence, comorbid active psychiatric illnesses, poor social support, and high expressed emotion in living environments (P < 0.05). The attribution of symptoms to social and cultural values (97%) and a poor knowledge of psychosis by family members (88%) was also prevalent. In addition to many well-documented factors associated with psychotic relapse, beliefs in social and cultural myths and values were found to be an important, and perhaps treatable, factor associated with relapse of psychosis in Pakistan. The provision of evidence-based psychotherapeutic interventions, such as behaviour and family therapy and cognitive behaviour therapy for psychosis, could potentially ameliorate the relapse rate of psychosis in Pakistan., (© 2016 Australian College of Mental Health Nurses Inc.)

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.