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

Department of Psychology, Duke University, Durham, NC 27708, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 02/2010; 167(2):160-9. 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.

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    • "In their seminal work, Jones et al. (1994) reported developmental disruptions and cognitive impairments in children with later onset of schizophrenia. Various ensuing studies replicated those cognitive deficits prior to the onset of full-blown psychosis (e.g., MacCabe et al., 2008; MacCabe et al., 2013; Metzler et al., 2014; Müller et al., 2013; Reichenberg et al., 2010; Zammit et al., 2004). Broad scientific consensus now exists among experts that poor premorbid cognitive functioning is a risk factor for schizophrenia and other psychotic disorders (Khandaker et al., 2011; MacCabe, 2008). "
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    ABSTRACT: Evidence is growing that persons along the schizophrenia spectrum, i.e., those who also display subclinical psychotic symptoms, exhibit deficits across a broad range of neuropsychological domains. Because sex differences in the association between cognitive deficits and psychosis have thus far been mostly neglected, we believe that ours is the first study specifically focused upon those differences when examining the relationship between subclinical psychosis and processing speed. Using a sample of 213 persons from the general population from Zurich, Switzerland, psychotic symptoms were assessed with three different questionnaires including the Schizotypal Personality Questionnaire, an adaptation of the Structured Interview for Assessing Perceptual Anomalies, and the Paranoia Checklist. Processing speed was assessed with the WAIS digit-symbol coding test. Two higher-order psychosis domains were factor-analytically derived from the various psychosis subscales and then subjected to a series of linear regression analyses. The results demonstrate that in both men and women associations between subclinical psychosis domains and processing speed were weak to moderate (β ranging from -0.18 to -0.27; all p<0.05). However, we found no sex-differences in the interrelation of subclinical psychosis and processing speed (ΔR(2)<0.005; p>0.30). In conclusion, it appears that sex differences in psychosis manifest themselves only at the high end of the continuum (full-blown schizophrenia) and not across the sub-threshold range. The small magnitude of the effects reported herein conforms to the etiopathology of the disorder. Since schizophrenia and related disorders from the spectrum are assumed to be multifactorial diseases, it follows that many etiological components of small effect are involved. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Jun 2015 · Schizophrenia Research
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    • "Most studies on schizotypal traits have concentrated on adult samples, specifically on individuals with schizophrenia spectrum disorder or schizotypal disorder and their relatives . However, there is compelling evidence suggesting that, already many years before the onset of the illness, deviant behavioural and cognitive development is present in children who are later diagnosed with schizotypal personality disorder or schizophrenia spectrum disorders [10] [11] [12]. It is important to be able to measure schizotypal traits, preferably in childhood and adolescence, as it is necessary to focus on development before and during adolescence in order to gain insight into the processes of aberrant (neuro-)development that indicates risk for severe outcome in adulthood [13]. "
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    ABSTRACT: The increasing interest in dimensional approaches towards schizophrenia spectrum pathology calls for instruments that can be used to study developmental markers conveying risk for psychopathology prior to onset of the disorder. In this study we evaluated the Dutch child version (SPQ-C-D) of the Schizotypal Personality Questionnaire (SPQ) developed by Raine, in terms of reliability and factorial structure in comparison to SPQ data from two studies with adults. The 74-item SPQ-C-D was completed by 219 children and adolescents aged 9 to 18 years. Internal consistency was assessed and the factorial structure was analyzed using principal component analysis (PCA) and confirmatory factor analysis. Results showed that most of the subscales had high Cronbach's alphas, indicating good internal consistency. PCA resulted in three components, similar to the adult studies: Cognitive-Perceptual, Interpersonal, and Disorganization. The pattern of individual subscales loading on each of the components was identical to the original Raine study, except for one additional subscale loading on the Disorganization component. In addition, forcing Raine's factorial structure on our data with confirmatory factor analysis resulted in an overall adequate model fit. In conclusion, the SPQ-C-D appears to be a suitable dimensional measure of schizotypal traits in populations aged 9 to 18 years.
    Full-text · Article · Mar 2015
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    • "The effects of AHR signaling on human brain development have been studied in geographic areas polluted with TCDD or related chemicals. Infant boys born in these regions show subtle deficits in growth rates, neurodevelopmental measures at 4 months and motor and language deficits at 3 years (Nishijo et al., 2012Nishijo et al., , 2014), consistent with the subtle morphological, motor, and cognitive deficits found during early childhood in schizophrenia (Reichenberg et al., 2010) and the genetic overlap between autism and schizophrenia (Stefansson et al., 2014). Interestingly, Δ 9 Tetrahydrocannabinol (THC) and kynurenine, two factors implicated in the etiology of schizophrenia, activate the AHR (Roth et al., 2001;Opitz et al., 2011). "
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    ABSTRACT: Neuropathological changes of the hippocampus have been associated with psychotic disorders such as schizophrenia and bipolar disorder. Recent work has particularly implicated hippocampal GABAergic interneurons in the pathophysiology of these diseases. However, the molecular mechanisms underlying structural and cellular hippocampal pathology remain poorly understood. We used data from comprehensive difference-in-gel electrophoresis (2-D DIGE) investigations of postmortem human hippocampus of people with schizophrenia and bipolar disorder, covering the acidic (isoelectric point (pI) between pH4 and 7) and, separately, the basic (pI between pH6 and 11) sub-proteome, for Ingenuity Pathway Analysis (IPA) of implicated protein networks and pathways. Comparing disease and control cases, we identified 58 unique differentially expressed proteins in schizophrenia, and 70 differentially expressed proteins in bipolar disorder, using mass spectrometry. IPA implicated, most prominently, 14-3-3 and aryl hydrocarbon receptor signaling in schizophrenia, and gluconeogenesis/glycolysis in bipolar disorder. Both disorders were characterized by alterations of proteins involved in the oxidative stress response, mitochondrial function, and protein-endocytosis, -trafficking, -degradation, and -ubiquitination. These findings are interpreted with a focus on GABAergic interneuron pathology in the hippocampus. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Schizophrenia Research
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