Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study.
ABSTRACT Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders?
Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects.
Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression.
These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7-13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older.
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ABSTRACT: Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n = 8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs = 0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n = 154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular.NeuroImage 01/2014; 97:41–52. · 6.25 Impact Factor
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ABSTRACT: The assessment of quality of life in clinical practice in patients with schizophrenia The aim of the present article is to review QoL scales used in studies investigating patients with schizophrenia over the past 5 years, and to summarize the results of QoL assessment in clinical practice in these patients.. Literature available from January 2009 to December 2013 was identified in a PubMed search using the key words "quality of life" and "schizophrenia" and in a cross-reference search for articles that were particularly relevant. A total of n=432 studies used 35 different standardized generic and specific QoL scales in patients with schizophrenia. Affect-ive symptoms were major obstacles for QoL improvement in patients with schizophrenia. Though positive symp-toms, negative symptoms, and cognitive functioning may be seen as largely independent parameters from subjec-tive QoL, especially in cross-sectional trials, long-term studies confirmed a critical impact of early QoL improvement on long-term symptomatic and functional remission, as well as of early symptomatic response on long-term QoL. Results of the present review suggest that QoL is a valid and useful outcome criterion in patients with schizophrenia. As such, it should be consistently applied in clinical trials. Understanding the relationship between symptoms and functioning with QoL is important because interventions that focus on symptoms of psychosis or functioning alone may fail to improve subjective QoL to the same level. However, the lack of consensus on QoL scales hampers research on its predictive validity. Future research needs to find a consensus on the concept and measures of QoL and to test whether QoL predicts better outcomes with respect to remission and recovery under consideration of different treatment approaches in patients with schizophrenia.Dialogues in clinical neuroscience 06/2014; 16(2):185-195.
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ABSTRACT: Background Previous research has shown that people with psychotic disorders have impaired functioning prior to the onset of the illness. The goal of this study is to obtain a detailed, in depth, analysis of the characteristics of premorbid impairment. Methods In this study we examined summaries of interviews with 20 male adolescents who were later diagnosed with non-affective psychotic disorders and compared them to interviews conducted with 20 matched controls without psychiatric disorders. The current study applied a qualitative analysis, performed in the following stages: each interview was read thoroughly by two blinded raters with no a-priori hypothesis, and then key themes and statements were identified and organized into meaningful domains. Afterwards, the frequency of each item was calculated and comparisons between the groups were performed. Results Future non-affective psychotic disorder patients were more likely to be described as strange or different, be involved in violent behavior, experience difficulties in educational functioning and peer integration, deal with problems in everyday functioning and have an avoidant interpersonal conflict resolution style in comparison with matched controls without psychiatric disorders. In addition, future patients experienced more stressful life events and dealt with these stressors more poorly in comparison with controls. Conclusions The findings of this unique historical-prospective qualitative analysis of interviews performed before the onset of psychosis, confirmed previous findings of premorbid abnormality of future non-affective psychosis patients. Using qualitative analysis enabled obtaining a more in-depth understanding of the real-life experience of the premorbid period among patients with non-affective psychotic disorders.Schizophrenia Research: Cognition. 03/2014; 1(1):e35–e39.