Effectiveness of a low support, remotely accessible, cognitive remediation training programme for chronic psychosis: cognitive, functional and cortical outcomes from a single blind randomised controlled trial.

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.

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls.

Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10-5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.

Detecting facial emotion recognition deficits in schizophrenia using dynamic stimuli of varying intensities.

BACKGROUND: Deficits in facial emotion recognition have been associated with functional impairments in patients with Schizophrenia (SZ). Whilst a strong ecological argument has been made for the use of both dynamic facial expressions and varied emotion intensities in research, SZ emotion recognition studies to date have primarily used static stimuli of a singular, 100%, intensity of emotion. To address this issue, the present study aimed to investigate accuracy of emotion recognition amongst patients with SZ and healthy subjects using dynamic facial emotion stimuli of varying intensities. To this end an emotion recognition task (ERT) designed by Montagne (2007) was adapted and employed. METHODS: 47 patients with a DSM-IV diagnosis of SZ and 51 healthy participants were assessed for emotion recognition. Results of the ERT were tested for correlation with performance in areas of cognitive ability typically found to be impaired in psychosis, including IQ, memory, attention and social cognition. RESULTS: Patients were found to perform less well than healthy participants at recognising each of the 6 emotions analysed. Surprisingly, however, groups did not differ in terms of impact of emotion intensity on recognition accuracy; for both groups higher intensity levels predicted greater accuracy, but no significant interaction between diagnosis and emotional intensity was found for any of the 6 emotions. Accuracy of emotion recognition was, however, more strongly correlated with cognition in the patient cohort. DISCUSSION: Whilst this study demonstrates the feasibility of using ecologically valid dynamic stimuli in the study of emotion recognition accuracy, varying the intensity of the emotion displayed was not demonstrated to impact patients and healthy participants differentially, and thus may not be a necessary variable to include in emotion recognition research.

Neural effects of social environmental stress - an activation likelihood estimation meta-analysis.

BACKGROUND: Social environmental stress, including childhood abuse and deprivation, is associated with increased rates of psychiatric disorders such as schizophrenia and depression. However, the neural mechanisms mediating risk are not completely understood. Functional magnetic resonance imaging (MRI) studies have reported effects of social environmental stress on a variety of brain regions, but interpretation of results is complicated by the variety of environmental risk factors examined and different methods employed. METHOD: We examined brain regions consistently showing differences in blood oxygen level-dependent (BOLD) response in individuals exposed to higher levels of environmental stress by performing a coordinate-based meta-analysis on 54 functional MRI studies using activation likelihood estimation (ALE), including an overall sample of 3044 participants. We performed separate ALE analyses on studies examining adults (mean age ⩾18 years) and children/adolescents (mean age <18 years) and a contrast analysis comparing the two types of study. RESULTS: Across both adult and children/adolescent studies, ALE meta-analysis revealed several clusters in which differences in BOLD response were associated with social environmental stress across multiple studies. These clusters incorporated several brain regions, among which the right amygdala was most frequently implicated. CONCLUSIONS: These findings suggest that a variety of social environmental stressors is associated with differences in the BOLD response of specific brain regions such as the right amygdala in both children/adolescents and adults. What remains unknown is whether these environmental stressors have differential effects on treatment response in these brain regions.