Reduced Cortical Folding in Schizophrenia: An MRI Morphometric Study

Faculty of Medicine, University of Sāo Paulo, Rua Dr. Ovidio Pires de Campos s/n, 05403-010 Sāo Paulo SP, Brazil.
American Journal of Psychiatry (Impact Factor: 12.3). 10/2003; 160(9):1606-13. DOI: 10.1176/appi.ajp.160.9.1606
Source: PubMed


Although well documented, regional brain structural abnormalities in schizophrenia are nonspecific, and morphometric parameters show significant overlapping between patients and healthy comparison subjects. An increasing number of studies have focused on supraregional models involving abnormalities of the neuronal circuitry between cortical regions in schizophrenia. The aim of the present study was to investigate cortical folding as an index of the neuronal wiring in different subtypes of schizophrenia.
Magnetic resonance imaging measures of gyrification index in intervals of 3.6 mm along the total cerebral cortex were compared in 40 patients with DSM-IV schizophrenia and 20 healthy subjects. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and the Negative Symptom Rating Scale.
The schizophrenia patients showed significantly reduced bilateral cortical folding relative to healthy comparison subjects. Such reductions were more pronounced in those with the disorganized subtype and showed an inverse correlation with negative symptoms and a positive correlation with positive symptoms. The paranoid subtype showed reduced cortical folding that was restricted to the left hemisphere.
These results from a larger patient group confirm a previous report of reduced cortical folding in schizophrenia patients. They also suggest a distinct pattern of abnormality between schizophrenia subtypes regarding the process of cerebral lateralization and are in agreement with the neurodevelopmental hypothesis of schizophrenia.

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Available from: Wagner Gattaz, Jun 18, 2014
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    • ", Narr et al. [2004], Harris et al. [2004], Falkai et al. [2007] and Sallet et al. [2003] MRI gyrification Indices Mean increase in gyrification in right prefrontal region in males. Narr et al [2004] found significant increases in cortical folding in the right superior frontal cortex [Harris et al., 2004], in male but not female patients [Narr et al., 2004]; bilateral increase in SCHZ [Falkai et al., 2007] decrease on left [Sallet et al., 2003]. "
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    ABSTRACT: Sex differences in psychosis and their interaction with laterality (systematic departures from 50:50 left-right symmetry across the antero-posterior neural axis) are reviewed in the context of the X-Y gene hypothesis. Aspects of laterality (handedness/cerebral asymmetry/the torque) predict (1) verbal and non-verbal ability in childhood and across adult life and (2) anatomical, physiological, and linguistic variation relating to psychosis. Neuropsychological and MRI evidence from individuals with sex chromosome aneuploidies indicates that laterality is associated with an X-Y homologous gene pair. Within each mammalian species the complement of such X-Y gene pairs reflects their potential to account for taxon-specific sexual dimorphisms. As a consequence of the mechanism of meiotic suppression of unpaired chromosomes such X-Y gene pairs generate epigenetic variation around a species defining motif that is carried to the zygote with potential to initiate embryonic gene expression in XX or XY format. The Protocadherin11XY (PCDH11XY) gene pair in Xq21.3/Yp11.2 in probable coordination with a gene or genes within PAR2 (the second pseudo-autosomal region) is the prime candidate in relation to cerebral asymmetry and psychosis in Homo sapiens. The lately-described pattern of sequence variation associated with psychosis on the autosomes may reflect a component of the human genome's adjustment to selective pressures generated by the sexually dimorphic mate recognition system. © 2013 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by John Wiley and Sons, Ltd.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2013; 162(8). DOI:10.1002/ajmg.b.32202 · 3.42 Impact Factor
    • "In prematurely delivered human infants, cerebral cortical folding abnormalities have been observed, and premature birth is associated with subsequent behavioral and cognitive deficits that become apparent later in childhood (Dubois et al., 2008). Cortical folding abnormalities have also been identified in individuals with Williams syndrome (Van Essen et al., 2006b) and schizophrenia (Csernansky et al., 2008b; Harris et al., 2004; Sallet et al., 2003). In autistic individuals, anomalous cortical folding is observed when compared to age-matched controls (Hardan et al., 2004; Nordahl et al., 2007), and the effect on folding is related to the severity of the behavioral deficit (Nordahl et al., 2007). "
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    ABSTRACT: Folding of the cerebral cortical surface is a critical process in human brain development, yet despite decades of indirect study and speculation the mechanics of the process remain incompletely understood. Leading hypotheses have focused on the roles of circumferential expansion of the cortex, radial growth, and internal tension in neuronal fibers (axons). In this article, we review advances in the mathematical modeling of growth and morphogenesis and new experimental data, which together promise to clarify the mechanical basis of cortical folding. Recent experimental studies have illuminated not only the fundamental cellular and molecular processes underlying cortical development, but also the stress state and mechanical behavior of the developing brain. The combination of mathematical modeling and biomechanical data provides a means to evaluate hypothesized mechanisms objectively and quantitatively, and to ensure that they are consistent with physical law, given plausible assumptions and reasonable parameter values.
    03/2013; 29. DOI:10.1016/j.jmbbm.2013.02.018
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    • "Folding in the ferret has been thoroughly documented in seminal papers by Smart and McSherry [1] [2] and in more recent work based on MR imaging [3] [4] [5] and detailed histology [6]. Abnormal folding patterns in the human brain are associated with severe mental or emotional disorders [7] [8] [9] [10] [11]. Disturbances of cortical folding in humans 4 Author to whom any correspondence should be addressed. "
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    ABSTRACT: In humans and many other mammals, the cortex (the outer layer of the brain) folds during development. The mechanics of folding are not well understood; leading explanations are either incomplete or at odds with physical measurements. We propose a mathematical model in which (i) folding is driven by tangential expansion of the cortex and (ii) deeper layers grow in response to the resulting stress. In this model the wavelength of cortical folds depends predictably on the rate of cortical growth relative to the rate of stress-induced growth. We show analytically and in simulations that faster cortical expansion leads to shorter gyral wavelengths; slower cortical expansion leads to long wavelengths or even smooth (lissencephalic) surfaces. No inner or outer (skull) constraint is needed to produce folding, but initial shape and mechanical heterogeneity influence the final shape. The proposed model predicts patterns of stress in the tissue that are consistent with experimental observations.
    Physical Biology 01/2013; 10(1):016005. DOI:10.1088/1478-3975/10/1/016005 · 2.54 Impact Factor
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