Examining cognition across the bipolar / schizophrenia diagnostic spectrum

BACKGROUND: Cognitive impairments are well-established features of schizophrenia, but there is ongoing debate about the nature and degree of cognitive impairment in patients with schizoaffective disorder and bipolar disorder. We hypothesized that there is a spectrum of increasing impairment from bipolar disorder to schizoaffective disorder bipolar type, to schizoaffective disorder depressive type and schizophrenia. METHODS: We compared performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery between participants with schizophrenia (n = 558), schizoaffective disorder depressive type (n = 112), schizoaffective disorder type (n = 76), bipolar disorder (n = 78) and healthy participants (n = 103) using analysis of covariance with post hoc comparisons. We conducted an ordinal logistic regression to examine whether cognitive impairments followed the hypothesized spectrum from bipolar disorder (least severe) to schizophrenia (most severe). In addition to categorical diagnoses, we addressed the influence of symptom domains, examining the association between cognition and mania, depression and psychosis. RESULTS: Cognitive impairments increased in severity from bipolar disorder to schizoaffective disorder bipolar type, to schizophrenia and schizoaffective disorder depressive type. Participants with schizophrenia and schizoaffective disorder depressive type showed equivalent performance (d = 0.07, p = 0.90). The results of the ordinal logistic regression were consistent with a spectrum of deficits from bipolar disorder to schizoaffective disorder bipolar type, to schizophrenia/schizoaffective disorder depressive type (odds ratio = 1.98, p < 0.001). In analyses of the associations between symptom dimensions and cognition, higher scores on the psychosis dimension were associated with poorer performance (B = 0.015, standard error = 0.002, p < 0.001). LIMITATIONS: There were fewer participants with schizoaffective disorder and bipolar disorder than schizophrenia. Despite this, our analyses were robust to differences in group sizes, and we were able to detect differences between groups. CONCLUSION: Cognitive impairments represent a symptom dimension that cuts across traditional diagnostic boundaries

SCAILET: An intelligent assistant for satellite ground terminal operations

NASA Lewis Research Center has applied artificial intelligence to an advanced ground terminal. This software application is being deployed as an experimenter interface to the link evaluation terminal (LET) and was named Space Communication Artificial Intelligence for the Link Evaluation Terminal (SCAILET). The high-burst-rate (HBR) LET provides 30-GHz-transmitting and 20-GHz-receiving, 220-Mbps capability for wide band communications technology experiments with the Advanced Communication Technology Satellite (ACTS). The HBR-LET terminal consists of seven major subsystems. A minicomputer controls and monitors these subsystems through an IEEE-488 or RS-232 protocol interface. Programming scripts (test procedures defined by design engineers) configure the HBR-LET and permit data acquisition. However, the scripts are difficult to use, require a steep learning curve, are cryptic, and are hard to maintain. This discourages experimenters from utilizing the full capabilities of the HBR-LET system. An intelligent assistant module was developed as part of the SCAILET software. The intelligent assistant addresses critical experimenter needs by solving and resolving problems that are encountered during the configuring of the HBR-LET system. The intelligent assistant is a graphical user interface with an expert system running in the background. In order to further assist and familiarize an experimenter, an on-line hypertext documentation module was developed and included in the SCAILET software

A meta-analysis comparing cognitive function across the mood/psychosis diagnostic spectrum

Background The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder. Methods Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder. Results Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05). Conclusion Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder

A qualitative study of GP, nurse and practice manager views on using targeted case-finding to identify patients with COPD in primary care

‘Finding the missing millions’ with chronic obstructive pulmonary disease became part of the Department of Health strategy for England in 2010. Targeted case-finding within primary care is one potential pro-active strategy, but currently little is known about the views of healthcare professionals on this approach. In this study, 36 healthcare professionals (12 GPs, 14 nurses, and 10 practice managers) from 34 UK practices participated in semi-structured telephone interviews about targeted case-finding. Interviews followed an interview guide, were audio-recorded, transcribed verbatim, coded and analysed using ‘Framework Approach’. Most of those interviewed practiced opportunistic case-finding. The main perceived barriers to wider case-finding programmes were the resource implications associated with running such programmes and identifying more chronic obstructive pulmonary disease patients. Financial incentives, support from specialist clinicians, and comprehensive guidance were viewed as facilitators. While targeted case-finding is conceptually accepted by primary care staff, scepticism surrounding (1) the value of identifying those with mild disease and (2) the availability of effective targeted case-finding methods, may lead some to favour an opportunistic approach. Key concerns were a lack of unequivocal evidence for the relative benefits vs. disadvantages of diagnosing patients earlier, and resource constraints in an already over-burdened system. Barriers to practical implementation of case-finding studies may be addressed with financial, human and educational resources, such as additional staff to undertake searches and perform spirometry tests, and practical and educational support from specialist teams

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Background It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. Methods Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. Results The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. Conclusions Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Background It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. Methods Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. Results The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. Conclusions Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder

Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BD cases, 2966 (67%) female, mean age-at-interview 46 [sd 12] years, from the BD Research Network (BDRN) were included in the final analyses. For comparison genotypic data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland were included. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms