Cognitive and social functioning correlates of employment among people with severe mental illness

We assess how social and cognitive functioning is associated to gaining employment for 213 people diagnosed with severe mental illness taking part in employment programs in Andalusia (Spain). We used the Repeatable Battery for the Assessment of Neuropsychological Status and the Social Functioning Scale and conducted two binary logistical regression analyses. Response variables were: having a job or not, in ordinary companies (OCs) and social enterprises (SEs), and working in and OC or not. There were two variables with significant adjusted odds ratios for having a job: “attention” and “Educational level”. There were five variables with significant odds ratios for having a job in an OC: “Sex”, “Educational level”, “Attention”, “Communication”, and “Independence-competence”. The study looks at the possible benefits of combining employment with support and social enterprises in employment programs for these people and underlines how both social and cognitive functioning are central to developing employment models

Caring for Caregivers (C4C): study protocol for a pilot feasibility randomised control trial of Positive Written Disclosure for older adult caregivers of people with psychosis

Background: The caregivers of people who experience psychosis are themselves at risk of developing physical and mental health problems. This risk is increased for older adult caregivers who also have to manage the lifestyle and health changes associated with ageing. As a consequence, older adult caregivers are in particular need of support; we propose a Written Emotional Disclosure (WED) intervention, called Positive Written Disclosure (PWD). Methods/design: This is a pilot randomised controlled trial of PWD compared to a neutral writing control and a no writing condition. We aim to recruit 60 participants, 20 in each arm. This study will utilise a mixed-methods approach and collect quantitative (questionnaires) and qualitative (interviews) data. Quantitative data will be collected at baseline and 1, 3, and 6 months post baseline. Participants who complete a writing task (PWD or neutral writing control) will be invited to complete an exit interview to discuss their experiences of the intervention and study. The study is supported by a patient and public involvement group. Discussion: The results of this trial will determine whether a definitive trial is justified. If so, the quantitative and qualitative findings will be used to refine the intervention and study protocols

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age. OBJECTIVE: To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. DESIGN, SETTING, AND PARTICIPANTS: This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. MAIN OUTCOMES AND MEASURES: We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age. RESULTS: We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers

Cigarette Smoking and Cognitive Function in Chinese Male Schizophrenia: A Case-Control study

Schizophrenic patients have higher smoking rates than the general population. Studies show that smoking may be a form of self-medication in an attempt to alleviate cognitive deficits in schizophrenic patients of European background. This study examined the relationships between smoking and cognitive deficits in Chinese schizophrenic patients, which have previously received little systemic study. We recruited 580 male chronic patients meeting DSM-IV criteria for schizophrenia and 175 male control subjects who were matched on age and education. The subjects completed a detailed cigarette smoking questionnaire, the Fagerstrom Test for Nicotine Dependence (FTND), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). All five RBANS subscales except for the Visuospatial/Constructional index showed significantly lower cognitive performance for schizophrenics than normal controls. The schizophrenic smokers scored lower than the schizophrenic non-smokers on the RBANS total score and the Visuospatial/Constructional and Immediate Memory indices. Similarly, the control smokers scored lower than the control non-smokers on the RBANS total score and the Immediate Memory index . Also, the schizophrenic smokers consistently performed the poorest on the cognitive domains of the RBANS. Among the schizophrenic patients, smokers displayed significantly fewer negative symptoms than non-smokers. Using multivariate regression analysis the following variables were independently associated with the RBANS total score: years of education, PANSS negative symptom score, age at schizophrenia onset, and number of hospitalizations. Our results show that smoking is associated with significant cognitive impairment in both schizophrenic patients and normal controls, but the smokers with schizophrenia had a reduced level of negative symptoms, suggesting that the benefits of smoking for those with schizophrenia may be limited to certain aspects of a given clinical phenotype

Deficits in Implicit Attention to Social Signals in Schizophrenia and High Risk Groups: Behavioural Evidence from a New Illusion

Background An increasing body of evidence suggests that the apparent social impairments observed in schizophrenia may arise from deficits in social cognitive processing capacities. The ability to process basic social cues, such as gaze direction and biological motion, effortlessly and implicitly is thought to be a prerequisite for establishing successful social interactions and for construing a sense of "social intuition." However, studies that address the ability to effortlessly process basic social cues in schizophrenia are lacking. Because social cognitive processing deficits may be part of the genetic vulnerability for schizophrenia, we also investigated two groups that have been shown to be at increased risk of developing schizophrenia-spectrum pathology: first-degree relatives of schizophrenia patients and men with Klinefelter syndrome (47,XXY). Results We compared 28 patients with schizophrenia, 29 siblings of patients with schizophrenia, and 29 individuals with Klinefelter syndrome with 46 matched healthy control subjects on a new paradigm. This paradigm measures one's susceptibility for a bias in distance estimation between two agents that is induced by the implicit processing of gaze direction and biological motion conveyed by these agents. Compared to control subjects, patients with schizophrenia, as well as siblings of patients and Klinefelter men, showed a lack of influence of social cues on their distance judgments. Conclusions We suggest that the insensitivity for social cues is a cognitive aspect of schizophrenia that may be seen as an endophenotype as it appears to be present both in relatives who are at increased genetic risk and in a genetic disorder at risk for schizophrenia-spectrum psychopathology. These social cue-processing deficits could contribute, in part, to the difficulties in higher order social cognitive tasks and, hence, to decreased social competence that has been observed in these groups

The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment

Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Importance: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. Objectives To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Design, Setting, and Participants: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Main Outcomes and Measures: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Results: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. Conclusions and Relevance: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score