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


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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    • "We will consider both the synchronic and diachronic dimensions in relation to the influential neurodevelopmental model of schizophrenia. In this model, noxious factors interfere with normal maturational brain processes during early stages of development, generating during childhood and adolescence neurologic (and concomitant subjective) abnormalities that at some point finally eventuate in the full-blown clinical syndrome (Gogtay et al., 2004; Insel, 2010; Parnas et al., 1996; Piper et al., 2012; Rapoport et al., 1999; Thompson and Levitt, 2010). "
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    DESCRIPTION: Schizophrenia is a heterogeneous syndrome, varying between persons and over course of illness. In this and a companion article, we argue that adequate comprehension of this condition or set of conditions may require combining a phenomenological perspective emphasizing disorders of basic-self experience (“ipseity disturbance”) with a multidimensional appreciation of possible neurobiological correlates—both primary and secondary. Previous attempts to link phenomenology and neurobiology generally focus on a single neurocognitive factor. We consider diverse aspects of schizophrenia symptomatology in light of a diverse, albeit interacting, set of neurocognitive abnormalities, examining both synchronic (structural) interdependence and diachronic (temporal) succession. In this first article we focus on the primary or foundational role of early of perceptual and motoric disturbances that affect perceptual organization and especially intermodal or multisensory perceptual integration (“perceptual dys-integration”). These disturbances are discussed in terms of their implications for three interconnected aspects of selfhood in schizophrenia, primary forms of: disrupted “hold” or “grip” on the world, hyperreflexivity, diminished self-presence (self-affection). Disturbances of organization or integration imply forms of perceptual incoherence or diminished cognitive coordination. The effect is to disrupt one’s ability to apprehend the world in holistic, vital, or contextually grounded fashion, or to fully identify with or experience the unity of one’s own body or thinking—thereby generating an early and profound (albeit often subtle) disruption or diminishment of basic or core self and of the sense of existing in a coherent world. We discuss interrelationships or possible complementarities between these three aspects, and consider their relevance for a neurodevelopmental account of schizophrenia.
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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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