Neuropsychology of the prodrome to psychosis in the NAPLS Consortium: Relationship to family history and conversion to psychosis

Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Archives of general psychiatry (Impact Factor: 14.48). 06/2010; 67(6):578-88. DOI: 10.1001/archgenpsychiatry.2010.66
Source: PubMed


Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions.
To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis.
Longitudinal study with 2(1/2) years of follow-up.
Eight centers participating in the North American Prodrome Longitudinal Study.
Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations.
A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status.
Global ("composite") neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion.
These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment.

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Available from: Eric Meyer, Jan 08, 2014
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    • "In contrast to the aforementioned clinical characteristics, cognitive and executive functioning has been shown to be remarkably stable over time (Heaton et al., 2001; Hoff et al., 1999) with similar deficits observed during the first-episode of psychosis and chronic course of the disorder (Sponheim et al., 2010). Furthermore, deficits in multiple cognitive domains seem to predate the onset of clinical symptoms (Lencz et al., 2006; Seidman et al., 2010) and a review over 65 studies (Torrey, 2002) confirmed that neuropsychological impairments are also observable in medication-naïve patients. "
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    ABSTRACT: Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015. Published by Elsevier Ireland Ltd.
    08/2015; 234(1). DOI:10.1016/j.pscychresns.2015.08.008
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    • "This could be an important time for early intervention before the onset of full blown psychosis and further cognitive and functional deterioration. Since these CHR individuals already evidence cognitive deficits, which increase around the time of conversion (Seidman et al., 2010; Fusar-Poli et al., 2012a), cognition is an excellent treatment target. Furthermore, treatments targeting cognition may consequently Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Individuals at clinical high risk (CHR) of psychosis evidence cognitive deficits. Given suggestions that deficits in cognition are related to poor functional outcome, cognition is a good treatment target. The aim of this study was to test the efficacy of cognitive remediation therapy (CRT) in improving cognition of CHR individuals. Participants were tested at baseline, immediately following CRT and 9 months post-baseline. The mixed effects modelling demonstrated no differences in cognition between the experimental group and the control group at any time point. For the experimental group, however, there was a trend towards improvement in speed of processing between baseline and 9-month follow-up (t(29)=-2.91, P=0.06) and at post-CRT compared to 9-month follow-up (t(29)=-2.99, P<0.05). In the control group, significant improvements in working memory were observed between post-CRT and 9-month follow-up (t(29)=-3.06, P<0.05). Despite significant improvements in social functioning in the intervention group between baseline and 9-month follow-up (t(28)=-3.26, P<0.05), these improvements were not correlated with cognition. There were trends towards improvement and no trends of decline in the two groups. While CRT may be valuable for individuals at CHR, the type of intervention employed needs to be carefully considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 11/2014; 225(1-2). DOI:10.1016/j.psychres.2014.10.021 · 2.47 Impact Factor
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    • "Regression analysis revealed that, within the groups at risk for psychosis (HR and UHR), a poor result in the speed domain was the most reliable predictor of an affiliation to the late UHR state. Other researchers have also determined that psychomotor speed is more consistent (Seidman et al. 2010; Kelleher et al. 2013) than reported (non-speed-dependent) deficits in working memory and executive functioning (Hawkins et al. 2004; Gschwandtner et al. 2006; Keefe et al. 2006; Niendam et al. 2006; Pukrop et al. 2006). "
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    ABSTRACT: BACKGROUND: Neurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains. METHOD: This study included 207 help-seeking individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar disorder (HRBip; n = 30), who were compared with persons comprising a matched, healthy control group (CG; n = 50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses. RESULTS: The performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p = 0.01). CONCLUSIONS: Performances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itself.
    Psychological Medicine 06/2014; FirstView:1-13. DOI:10.1017/S0033291714001007 · 5.94 Impact Factor
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