Static and Dynamic Cognitive Deficits in Childhood Precede Adult Schizophrenia: A 30-Year Study

ArticleinAmerican Journal of Psychiatry 167(2):160-9 · February 2010with18 Reads
Impact Factor: 12.30 · DOI: 10.1176/appi.ajp.2009.09040574 · Source: PubMed

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.

    • "In fact, WM deficits have been confirmed both before and after the first episode of the disorder[16][17][18] . Individuals with schizophrenia seem to follow specific deterioration trajectories in WM throughout their lives[17, 19, 20]. Furthermore, minor WM impairment is evident in first-degree relatives of people with schizophrenia and other individuals at familial-risk[21][22][23], suggesting a genetic contribution [24, 25]. "
    [Show abstract] [Hide abstract] ABSTRACT: Psychotic Experiences (PEs) during adolescence index increased risk for psychotic disorders and schizophrenia in adult life. Working memory (WM) deficits are a core feature of these disorders. Our objective was to examine the relationship between PEs and WM in a general population sample of young people in a case control study. 4744 individuals of age 17-18 from Bristol and surrounding areas (UK) were analyzed in a cross-sectional study nested within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. The dependent variable was PEs, assessed using the semi-structured Psychosis-Like Symptom Interview (PLIKSi). The independent variable was performance on a computerized numerical n-back working memory task. Signal-Detection Theory indices, including standardized hits rate, false alarms rate, discriminability index (d') and response bias (c) from 2-Back and 3-Back tasks were calculated. 3576 and 3527 individuals had complete data for 2-Back and 3-Back respectively. Suspected/definite PEs prevalence was 7.9% (N = 374). Strongest evidence of association was seen between PEs and false alarms on the 2-Back, (odds ratio (OR) = 1.17 [95% confidence intervals (CI) 1.01, 1.35]) and 3-back (OR = 1.35 [1.18, 1.54]) and with c (OR = 1.59 [1.09, 2.34]), and lower d' (OR = 0.76 [0.65, 0.89]), on the 3-Back. Adjustment for several potential confounders, including general IQ, drug exposure and different psycho-social factors, and subsequent multiple imputation of missing data did not materially alter the results. WM is impaired in young people with PEs in the general population. False alarms, rather than poor accuracy, are more closely related to PEs. Such impairment is consistent with different neuropsychological models of psychosis focusing on signal-to-noise discrimination, probabilistic reasoning and impaired reality monitoring as a basis of psychotic symptoms.
    Full-text · Article · Apr 2016 · PLoS ONE
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    • "It has also been suggested that IQ scores tend to deteriorate during transition to illness (Cosway et al., 2000; Caspi et al., 2003; Lencz et al., 2006). Similarly, data from the follow-up studies suggest that there is a deterioration of up to 10 points on IQ scores, after onset of psychosis, in a proportion of affected individuals (Aylward et al., 1984; Reichenberg et al., 2005 Reichenberg et al., , 2010). Recent studies of individuals at high risk of developing psychosis indicate that a significant proportion have problems with learning and have low IQ scores before the onset of illness (Keshavan et al., 2004Keshavan et al., , 2005 Johnstone et al., 2005). "
    [Show abstract] [Hide abstract] ABSTRACT: Epidemiological studies report high rates of schizophrenia in individuals with intellectual disability (ID). However, this subject has not been reviewed systematically. We aim to review studies that report the prevalence of nonaffective psychosis in a population with ID and estimate the prevalence of schizophrenia in this population. We performed a literature search using the PsychINFO, MEDLINE and EMBASE (from inception to 2 October 2014). We performed a manual search of citations from relevant papers identified through the databases. We identified 887 titles and after screening abstracts, identified 60 full-text articles. We identified 25 studies with 27 datasets for inclusion in the systematic review and meta-analysis. The prevalence rate was at least three times higher than the general population. There was a wide variation in the methodology, setting and sample size of the studies. Only one study reported a prevalence rate lower than the general population. The prevalence of psychosis in a population with ID is at least three times higher than that in the general population.
    No preview · Article · Apr 2016 · Psychiatric genetics
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    • "While the current findings illustrate differences in working memory function and brain network configuration in those with persistent PEs compared with HCs, it is uncertain how this relates to the very phenomena that characterize these groups. More specifically , does the presence of PEs cause alterations in working memory function or do changes in cognitive development lead to the manifestation of PEs? Though trajectories vary for specific cognitive functions, numerous studies on premorbid neuropsychological functioning have reported IQ deficits prior to the onset of schizophrenia (Woodberry et al. 2008; Reichenberg et al. 2010; Dickson et al. 2012; Meier et al. 2014), which do not seem to progress with age nor in the presence of prodromal psychotic symptoms (Woodberry et al. 2008 ). Neuroimaging studies also report a progressive decline in gray and white matter structures after the onset of psychosis compared with the prodromal stage (Pantelis et al. 2005; Peters and Karlsgodt 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs. © The Author 2015. Published by Oxford University Press.
    Full-text · Article · Aug 2015 · Cerebral Cortex
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