Cognitive deficits and functional outcome in schizophrenia

Cognitive dysfunction is a core feature of schizophrenia. Deficits are moderate to severe across several domains, including attention, working memory, verbal learning and memory, and executive functions. These deficits pre-date the onset of frank psychosis and are stable throughout the course of the illness in most patients. Over the past decade, the focus on these deficits has increased dramatically with the recognition that they are consistently the best predictor of functional outcomes across outcome domains and patient samples. Recent treatment studies, both pharmacological and behavioral, suggest that cognitive deficits are malleable. Other research calls into question the meaningfulness of cognitive change in schizophrenia. In this article, we review cognitive deficits in schizophrenia and focus on their treatment and relationship to functional outcome

Socioeconomic inequalities in adolescent smoking behaviour and neighbourhood access to tobacco products.

Youth smoking is an important aspect of tobacco research as most adult smokers first experiment with and initiate tobacco use during their adolescence. Policy makers and researchers have given youth smoking issues a significant amount of attention over the last 20 years and this has led to significant reductions in youth smoking prevalence in New Zealand. More recently the decline in youth smoking prevalence has reached a plateau. Evidence now shows that while overall smoking prevalence has reduced, inequalities between ethnic and social groups has actually increased. This is an international trend. Young people living in low socioeconomic status areas and belonging to minority ethnic groups are at much higher risk of being a current smoker than their less deprived peers. A number of overseas studies have investigated the spatial relationship between aspects of the neighbourhood environment and adolescent smoking behaviour in an attempt to identify the most at risk groups. In particular the effect of neighbourhood socioeconomic status and the degree of access to tobacco outlets is believed to influence adolescent smoking behaviour. In New Zealand analysis of this type has mainly focused on adult smoking behaviour and the effect of tobacco outlet access is as yet unstudied. This study examines the effect of neighbourhood and high school socioeconomic status on adolescent smoking behaviour, attitudes and beliefs in Christchurch. Using information from the 2006 New Zealand Census, spatial variations in reported neighbourhood smoking prevalence have been examined. In addition, analysis of responses to smoking questions in the 2008 Year 10 In-depth Survey have been carried out show how school socioeconomic status can influence underlying attitudes and beliefs young people hold towards smoking and tobacco products. Spatial analysis has also been performed on the census dataset to investigate the relationship between neighbourhood access to tobacco outlets and youth smoking behaviour after controlling for neighbourhood deprivation. To supplement each of these quantitative data sources, focus group interviews were carried out at two high schools (one low and one high socioeconomic status). Findings from these interviews are presented as further insight into adolescent attitudes and beliefs towards smoking. Results of this research show that there is a socioeconomic effect at both a neighbourhood and school level on all adolescent smoking behaviours, attitudes and beliefs examined, except for smoking cessation. There is also evidence of greater access to tobacco outlets in low socioeconomic neighbourhoods but not so around high schools. Increased access to tobacco outlets is linked to increased adolescent smoking prevalence, more so among females than males, but this relationship disappeared in age groups 20 and above

Guest Editors' Introduction

‘I shall have to speak of things, of which I cannot speak’, writes Samuel Beckett in The Unnameable, ‘but also, which is even more interesting, but also that I, which is if possible even more interesting, that I shall have to, I forget, no matter’. Listening to the voice of folly can be like this: an endless flow of inconsistencies, of contradictions, sayings and unsayings; a tantalising, mischievous mockery of speech –unable to go on, unable to end. And yet – as this volume shows – we are irresistibly drawn to folly, its promises, its whispers of ‘even more interesting’ things: of how we are split between conscious and unconscious, familiar and unfamiliar, same and other. For psychoanalysis, folly is not only a site of hidden truths; it is also, perhaps more importantly, a source of unconscious freedom, a momentary escape from our obsession with rules and order. According to Christopher Bollas, the unconscious self is like a fool, who ‘raises potentially endless questions about diverse and disparate issues’ and thereby provides us with a ‘separate sense’, which opens us to others and to our own creative potential. As Rachel Bowlby elegantly puts it, folly is a ‘soul-mole’, forever shovelling our secrets out into the light: ‘there’s no possible moment of release or resignation when the mole might stop vainly, interminably working away’. Folly’s subversive, creative soliloquies reveal to us a psychic ‘underground repertoire of secrets’; they challenge our established knowledge and invite us, as Bolwby shows, to endless, titillating games of ‘suppression and confession’. For Anne Duprat, this deep-seated playfulness explains folly’s close relation to fiction: what makes them so atone is their ‘capacity of creating alternative representations of the world — and thus of re-figuring the world depicted by reason or history – […] but also their paradoxical structure, and hence the instability of their speech acts, which deny, suspend, or do not seriously guarantee the truth of their statements’. (First paragraph

The course and correlates of everyday functioning in schizophrenia

AbstractPreviously institutionalized older patients with schizophrenia show changes in cognitive and functional capacity over time. This study examined changes in real-world functioning in a sample of people with schizophrenia who varied in their history of long-term institutionalization and related changes in real world functioning to changes in cognition and functional capacity over the follow-up period.Older patients with schizophrenia (n=111) were examined with assessments of cognitive functioning, functional capacity, clinical symptoms, and everyday functioning. They were then followed up to 45 months and examined up to two times. Mixed-model regression was used to examine changes in real-world functioning in social, everyday living, and vocational domains over the follow-up period and identify potential predictors of change.Everyday functioning worsened over time in all three domains. Although length of longest hospitalization predicted worsening, this influence was eliminated when the course of functional capacity was used to predict the course of everyday functioning. For both vocational and everyday living domains, as well as the composite score on functional status, worsening in performance based measures of everyday functioning and social competence predicted worsening in real world functioning. Changes in negative symptoms further predicted worsening in the everyday living domain.Worsening in everyday functioning is found in people with schizophrenia and those with a history of greater chronicity and severity of illness seem more affected. These influences seem to be expressed through worsening in the ability to perform everyday functional skills. Potential causes of these changes and implications for reducing these impairments are discussed

Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder:Study protocol for a randomized controlled trial

Abstract Background Cognitive impairment is present in bipolar disorder (BD) during the acute and remitted phases and hampers functional recovery. However, there is currently no clinically available treatment with direct and lasting effects on cognitive impairment in BD. We will examine the effect of a novel form of cognitive remediation, action-based cognitive remediation (ABCR), on cognitive impairment in patients with BD, and explore the neural substrates of potential treatment efficacy on cognition. Methods/design The trial has a randomized, controlled, parallel-group design. In total, 58 patients with BD in full or partial remission aged 18–55 years with objective cognitive impairment will be recruited. Participants are randomized to 10 weeks of ABCR or a control group. Assessments encompassing neuropsychological testing and mood ratings, and questionnaires on subjective cognitive complaints, psychosocial functioning, and quality of life are carried out at baseline, after 2 weeks of treatment, after the end of treatment, and at a six-month-follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and 2 weeks into treatment. The primary outcome is a cognitive composite score spanning verbal memory, attention, and executive function. Two complete data sets for 52 patients will provide a power of 80% to detect a clinically relevant between-group difference on the primary outcome. Behavioral data will be analyzed using mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert Analysis Tool (FEAT). Early treatment-related changes in neural activity from baseline to week 2 will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest and with an exploratory whole-brain analysis. Discussion The results will provide insight into whether ABCR has beneficial effects on cognition and functioning in remitted patients with BD. The results will also provide insight into early changes in neural activity associated with improvement of cognition, which can aid future treatment development. Trial registration Clinicaltrials.gov, NCT03295305. Registered on 26 September 2017

Examining the association of life course neurocognitive ability with real-world functioning in schizophrenia-spectrum disorders

There is considerable variability in neurocognitive functioning within schizophrenia-spectrum disorders, and neurocognitive performance ranges from severe global impairment to normative performance. Few investigations of neurocognitive clusters have considered the degree to which deterioration relative to premorbid neurocognitive abilities is related to key illness characteristics. Moreover, while neurocognition and community functioning are strongly related, understanding of the sources of variability in the association between these two domains is also limited; it is unknown what proportion of participants would over-perform or under-perform the level of functioning expected based on current neurocognitive performance vs. lifelong attainment. This study examined data from 954 outpatients with schizophrenia-spectrum disorders across three previous studies. Neurocognition, community functioning, and symptoms were assessed. Neurocognitive subgroups were created based on current neurocognition, estimated premorbid IQ, and degree of deterioration from premorbid using z-score cut-offs; functional subgroups were created with cluster analysis based on the Specific Level of Functioning Scale and current neurocognition. The sample was neurocognitively heterogeneous; 65% displayed current neurocognitive impairment and 84% experienced some level of deterioration. Thirty percent of our sample was relatively higher functioning despite significant neurocognitive impairment. Individuals with better community functioning, regardless of neurocognitive performance, had lower symptom severity compared to those with worse functioning. These results highlight the variability in neurocognition and its role in functioning. Understanding individual differences in neurocognitive and functional profiles and the interaction between prior and current cognitive functioning can guide individualized treatment and selection of participants for clinical treatment studies

Deletion of the dominant autoantigen in NZB mice with autoimmune hemolytic anemia : Effects on autoantibody and T-helper responses

Peer reviewedPublisher PD

Iron in the Sargasso Sea (Bermuda Atlantic Time-series Study region) during summer : eolian imprint, spatiotemporal variability, and ecological implications

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 19 (2005): GB4006, doi:10.1029/2004GB002445.We report iron measurements for water column and aerosol samples collected in the Sargasso Sea during July-August 2003 (summer 2003) and April-May 2004 (spring 2004). Our data reveal a large seasonal change in the dissolved iron (dFe) concentration of surface waters in the Bermuda Atlantic Time-series Study region, from ∼1–2 nM in summer 2003, when aerosol iron concentrations were high (mean 10 nmol m−3), to ∼0.1–0.2 nM in spring 2004, when aerosol iron concentrations were low (mean 0.64 nmol m−3). During summer 2003, we observed an increase of ∼0.6 nM in surface water dFe concentrations over 13 days, presumably due to eolian iron input; an estimate of total iron deposition over this same period suggests an effective solubility of 3–30% for aerosol iron. Our summer 2003 water column profiles show potentially growth-limiting dFe concentrations (0.02–0.19 nM) coinciding with a deep chlorophyll maximum at 100–150 m depth, where phytoplankton biomass is typically dominated by Prochlorococcus during late summer.Funding for this work was provided by the U.S. National Science Foundation (OCE-0222053 to P. N. S., OCE-0222046 to T. M. C., and OCE-0241310 to D. J. M.), the U.S. National Aeronautics and Space Administration (NAG5-11265 to D. J. M.), the Australian Research Council (DP0342826 to A. R. B.), the Antarctic Climate and Ecosystems Cooperative Research Center, and the H. Unger Vetlesen Foundation

N6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation

© 2018 National Academy of Sciences. All Rights Reserved. The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington’s disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA ad-ducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems