Self-defining memories predict engagement in structured activity in First Episode Psychosis, independent of neurocognition and metacognition

Background: Self-defining memories (SDM) are vivid personal memories, related to narrative identity. Individuals with schizophrenia report less specific, more negative, and extract less meaning from these memories compared to control groups. Self-defining memories have been shown to be predicted by neurocognition, associated with metacognition, and linked to goal outcomes in healthy controls. As neurocognition and metacognition are known predictors of poor functioning in psychosis, self-defining memories may also be a predictor. No study has assessed the relationship to functioning or pattern of SDMs in First Episode Psychosis. Methods: This was a cross-sectional study involving 71 individuals with First Episode Psychosis (FEP) and 57 healthy controls who completed a self-defining memories questionnaire. FEP participants completed measures of neurocognition, metacognition (Metacognitive Assessment Interview), functional capacity (The UCSD Performance-Based Skills Assessment) and functional outcome (Time-Use Survey). Results: Self-defining memories reported by individuals with FEP were less integrated compared to healthy controls. Within the FEP sample, holding less specific memories was associated with engagement in significantly fewer hours of structured activity per week and specificity of SDMs mediated the relationship between neurocognition and functional outcome, independent of metacognition. Conclusion: This is the first study to assess SDMs in FEP and to explore the important role of SDMs on clinical outcomes, compared to healthy controls. This study suggests that elaborating on specific self-defining memories is a valid therapeutic target and may be considered a tool to improve daily functioning in FEP

Associations between responses to voices, distress and appraisals during daily life: an ecological validation of the cognitive behavioural model

Background Cognitive models propose that behavioural responses to voices maintain distress by preventing disconfirmation of negative beliefs about voices. We used Experience Sampling Methodology (ESM) to examine the hypothesized maintenance role of behavioural responses during daily life. Method Thirty-one outpatients with frequent voices completed a smartphone-based ESM questionnaire 10 times a day over 9 days, assessing voice-related distress; resistance and compliance responses to voices; voice characteristics (intensity and negative content); appraisals of voice dominance, uncontrollability and intrusiveness. Results In line with predictions, behavioural responses were associated with voice appraisals (dominance and uncontrollability), but not voice characteristics. Greater resistance and compliance were reported in moments of increased voice distress, but these associations did not persist after controlling for concurrent voice appraisals and characteristics. Voice distress was predicted by appraisals, and, unexpectedly, also by voice characteristics. As predicted, compliance and resistance were related to increases in distress at subsequent timepoints, whilst antecedent voice appraisals and characteristics had no such effect. Compliance, but not resistance, additionally predicted subsequent increases in voice uncontrollability. In both cases, the reverse models showed no association, indicating directional effects of responses on subsequent distress, and of compliance on uncontrollability appraisals. Conclusions These results provide support for the cognitive model by suggesting that momentary behavioural and emotional responses to voices are associated with concurrent negative voice appraisals. Findings suggest that behavioural responses may be driven by voice appraisals, rather than directly by distress, and may in turn maintain voice appraisals and associated distress during the course of daily life

Cognitive and metacognitive factors predict engagement in employment in individuals with First Episode Psychosis

Background: Research has demonstrated that cognitive abilities predict work outcomes in people with psychosis. Cognitive Remediation Programs go some way in improving work outcomes, but individuals still experience difficulty maintaining employment. Metacognition has been demonstrated to predict work performance in individuals with schizophrenia, but this but this has not yet been applied to First Episode Psychosis (FEP). This study assessed whether metacognition, intellectual aptitude and functional capacity can predict engagement in work and number of hours working in FEP. Methods: Fifty-two individuals with psychosis, from Early Intervention in Psychosis services, completed measures of IQ, metacognition (Metacognitive Assessment Interview), functional capacity (UPSA), and functional outcome (hours spent in structured activity per week, including employment). Results: Twenty-six participants (22 males, 4 females) were employed and twenty-six (22 males, 4 females) were not employed. IQ and metacognition were significantly associated with whether the individual was engaged in employment [IQ (p=.02) and metacognition (p=006)]. When controlling for IQ, metacognition (differentiation subscale) remained significant (p=.04). Next, including only those employed, no cognitive nor metacognitive factors predicted number of hours in employment. Discussion: This is the first study to directly assess metacognition as a predictor of work hours in people with FEP. This study highlights the importance of enhancing metacognitive ability in order to improve likelihood of, and engagement in, employment for those with FEP

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)

Background: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. Aim: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. Methods: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and a control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. Results: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. Conclusion: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors

Improving physical health and reducing substance use in psychosis - randomised control trial (IMPACT RCT): study protocol for a cluster randomised controlled trial

The National Institute for Health Research funds the IMPACT programme at King’s College London and South London and Maudsley NHS Foundation Trust (ref: RP-PG-0606-1049)

Deficits in neurite density underlie white matter structure abnormalities in first-episode psychosis

Background: Structural abnormalities across multiple white matter tracts are recognised in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterise microstructural white matter abnormalities for a deeper understanding of the developmental aetiology of psychosis. Methods: Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using Neurite Orientation Dispersion and Density Imaging (NODDI), a multi-shell diffusion-weighted MRI technique that distinguishes white matter fibre arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and controls and tested associations with age, symptom severity and medication. Results: Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fibre bundle arrangement (orientation dispersion index). There was no direct relationship with active symptomatology. FA decreased and orientation dispersion index increased with age in patients, but not controls, suggesting accelerated effects of white matter geometry change. Conclusions: Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of NODDI in psychosis, we found that processes compromising axonal fibre number, density, and myelination, rather than processes leading to spatial disruption of fibre organisation, are implicated in the aetiology of the disorder. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis

Hyperprolactinaemia in first episode psychosis - a longitudinal assessment

Little is known about hyperprolactinaemia (HPL) in first episode psychosis (FEP) patients. We investigated longitudinal changes in serum prolactin in FEP, and the relationship between HPL, and antipsychotic medication and stress. Serum prolactin was recorded in FEP patients at recruitment and again, 3 and 12 months later. HPL was defined as a serum prolactin level greater than 410 mIU/L (~19.3ng/ml) for males, and a serum prolactin level greater than 510 mIU/L (~24.1ng/ml) for females. From a total of 174 people with serum prolactin measurements at study recruitment, 43% (n=74) had HPL, whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12 months respectively. We observed higher serum prolactin levels in females versus males (p<0.001), and in antipsychotic treated (n=68) versus antipsychotic naïve patients (p<0.0001). Prolactin levels were consistently raised in FEP patients taking risperidone, amisulpride and FGAs compared to other antipsychotics. No significant relationship was observed between perceived 3 stress scores (β=7.13, t =0.21, df=11, p=0.0.84 95% CI -72.91-87.16), or objective life stressors (β=-21.74, t=-0.31, df=8, p=0.77 95% CI -218.57-175.09) and serum prolactin. Our study found elevated rates of HPL over the course of the first 12 months of illness. We found no evidence to support the notion that stress is related to elevated serum prolactin at the onset of psychosis

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

Holding blame at bay? ‘Gene talk’ in family members’ accounts of schizophrenia aetiology

We provide the first detailed analysis of how, for what purposes and with what consequences people related to someone with a diagnosis of schizophrenia use ‘gene talk'. The article analyses findings from a qualitative interview study conducted in London and involving 19 participants (mostly women). We transcribed the interviews verbatim and analysed them using grounded theory methods. We analyse how and for what purposes participants mobilized ‘gene talk' in their affectively freighted encounter with an unknown interviewer. Gene talk served to (re)position blame and guilt, and was simultaneously used imaginatively to forge family history narratives. Family members used ‘gene talk' to recruit forebears with no psychiatric diagnosis into a family history of mental illness, and presented the origins of the diagnosed family member's schizophrenia as lying temporally before, and hence beyond the agency of the immediate family. Gene talk was also used in attempts to dislodge the distressing figure of the schizophrenia-inducing mother. ‘Gene talk', however, ultimately displaced, rather than resolved, the (self-)blame of many family members, particularly mothers. Our article challenges the commonly expressed view that genetic accounts will absolve family members' sense of (self-)blame in relation to their relative's/relatives' diagnosis

An examination of polygenic score risk prediction in individuals with first-episode psychosis

Background Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. Methods The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. Results PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10−6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002). Conclusions PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP