Progressive Cortical Change During Adolescence in Childhood-Onset Schizophrenia

Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA.
Archives of General Psychiatry (Impact Factor: 14.48). 08/1999; 56(7):649-54. DOI: 10.1001/archpsyc.56.7.649
Source: PubMed

ABSTRACT Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence.
To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions.
A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups.
Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.

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Available from: Jeffrey S Bedwell, Sep 26, 2015
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    • "One study reported loss of corpus callosum (CC) volume over time (Keller et al., 2003b), which was not reported in Johnson et al. (2013a). Several studies showed greater progressive loss of temporal GM volume over time compared with healthy controls (Jacobsen et al., 1998; Rapoport et al., 1999; Gogtay et al., 2004b; James et al., 2004), but see Arango et al. (2012). There were even two studies reporting an absence of progressive brain changes in patients over the first 2–3 years of follow-up (James et al., 2002; James et al., 2004). "
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    ABSTRACT: Studies on longitudinal brain volume changes in patients with early-onset psychosis (EOP) are particularly valuable for understanding the neurobiological basis of brain abnormalities associated with psychosis. However, findings have not been consistent across studies in this population. We aimed to conduct a meta-analysis on progressive brain volume changes in children and adolescents with EOP. A systematic literature search of magnetic resonance imaging (MRI) studies comparing longitudinal brain volume changes in children and adolescents with EOP and healthy controls was conducted. The annualized rates of relative change in brain volume by region of interest (ROI) were used as raw data for the meta-analysis. The effect of age, sex, duration of illness, and specific diagnosis on volume change was also evaluated. Five original studies with 156 EOP patients (mean age at baseline MRI in the five studies ranged from 13.3 to 16.6years, 67.31% males) and 163 age- and sex-matched healthy controls, with a mean duration of follow-up of 2.46years (range 2.02-3.40), were included. Frontal gray matter (GM) was the only region in which significant differences in volume change over time were found between patients and controls (Hedges' g -0.435, 95% confidence interval (CI): -0.678 to -0.193, p<0.001). Younger age at baseline MRI was associated with greater loss of temporal GM volume over time in patients as compared with controls (p=0.005). Within patients, a diagnosis of schizophrenia was related to greater occipital GM volume loss over time (p=0.001). Compared with healthy individuals, EOP patients show greater progressive frontal GM loss over the first few years after illness onset. Age at baseline MRI and diagnosis of schizophrenia appear to be significant moderators of particular specific brain volume changes. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; DOI:10.1016/j.schres.2014.12.022 · 3.92 Impact Factor
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    • "Childhood-onset schizophrenia (COS) is a rare, severe form of the disorder with more marked neurodevelopmental impairments (Rapoport et al. 2005), thought to be neurobiologically, diagnostically and physiologically continuous with the adult disorder (Nicolson et al. 1999; Addington et al. 2005). In COS, progressive decreases in cortical gray-matter volume in frontal (11%), parietal (8.5%), and temporal lobes (7%) have been reported, as well as a progressive increase in ventricular volume (Rapoport et al. 1999; Sporn et al. 2003). The imaging data overall portray a fourfold greater reduction in cortical volume than in scans of healthy adolescent subjects. "
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    ABSTRACT: Hallucinations are a hallmark symptom of schizophrenia. Although they can occur in the auditory, visual, olfactory, gustatory and somatosensory modalities, approximately 70% of individuals diagnosed with schizophrenia report hallucinations in the auditory modality (Andreasen and Flaum 1991). Auditory hallucinations can occur in the context of a wide range of psychiatric disorders, but their prevalence is highest in patients with schizophrenia (American Psychiatric Association 2000). The present chapter focuses on auditory hallucinations in schizophrenia. Research findings on hallucinatory experiences in other disorders and in healthy individuals have been recently synthesized elsewhere and will not be covered here (Jardri et al. 2013; Blom and Sommer 2012).
    Brain Evolution, Language and Psychopathology in Schizophrenia, Edited by Paolo Brambilla, Andrea Marini, 01/2014: chapter Thought, hallucinations and schizophrenia: pages 153-167; Routledge., ISBN: 978-0-415-53764-3
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    • "While typically developing children were found to have a small decrease in cortical gray matter (~2%) in the frontal and parietal regions throughout adolescence, children with COS displayed exaggerated gray matter losses (~8%), involving the frontal, parietal, and temporal lobes. Of note, baseline IQ varied significantly between case and control groups in this data set (70 vs. 124) (21). "
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    ABSTRACT: Background: Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis. Methods: A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity. Results: In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning. Conclusion: The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.
    Frontiers in Psychiatry 12/2013; 4:175. DOI:10.3389/fpsyt.2013.00175
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