Abnormalities in structural covariance of cortical gyrification in schizophrenia (original) (raw)
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Schizophrenia Research, 2009
The etiologic factors underlying schizophrenia have been conceptualized as reflecting two largely genetic componentsthose unique to schizophrenia and those representing vulnerability to neurodevelopmental deviation in general. The Developmental Instability (DI) approach suggests that the latter can be indexed by minor physical anomalies (MPAs), which assess early prenatal growth abnormalities, and fluctuating anatomic asymmetries (FA), which reflects later deviations. Individuals with schizophrenia (N = 19) had elevated scores on both measures as compared to healthy controls (N = 23). Further, MPAs and FA were very highly correlated in the sample of individuals with schizophrenia but not in controls. In order to identify neuroanatomic variation linked with the unique factor, we conducted gray matter Voxel Based Morphometry analyses of group membership, with and without treating a composite measure of DI (based on FA, and MPAs) as a covariate. When DI was treated as a covariate, many more gray matter regions were found to statistically differ as a function of diagnosis. These results support the DI approach and suggest that the unique etiologic factors associated with schizophrenia lead to widespread gray matter volume reductions.
Schizophrenia Bulletin, 2005
The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an ''early neurodevelopmental'' lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre-or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre-and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness.
Rethinking schizophrenia in the context of normal neurodevelopment
Frontiers in cellular neuroscience, 2013
The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities s...
2016
Clinical heterogeneity presents important challenges to optimizing psychiatric diagnoses and treatments. Patients clustered within current diagnostic schema vary widely on many features of their illness, including their responses to treatments. As outlined by the American Psychiatric Association Diagnostic and Statistical Manual (DSM), psychiatric diagnoses have been refi ned since DSM was introduced in 1952. These diagnoses serve as the targets for current treatments and supported the emergence of psychiatric genomics. However, the Research Domain Criteria highlight DSM’s shortcomings, including its limited ability to encompass dimensional features linking patients across diagnoses. This chapter considers elements of the dimensional and categorical features of psychiatric diagnoses, with a particular focus on schizophrenia. It highlights ways that computational neuroscience approaches have shed light on both dimensional and categorical features of the biology of schizophrenia. It a...
NEURODEVELOPMENTAL AND NEUROPROGRESSIVE PROCESSES IN SCHIZOPHRENIA
Psychiatric Clinics of North America, 1998
Despite the wealth of neuroimaging and neuropathologic evidence for abnormalities of brain structure and function in schizophrenia that has evolved over the past two decades, considerably less is known of their origins or of how they might relate mechanistically to the clinical features and the course of the disorder.41 In the 1980s, there emerged renewed interest in an old and neglected question, the apparent answer to which continues to exert a powerful influence over contemporary research and theory: Do these abnormalities reflect a brain that was once normal but that became subject to some later pathological process (at or somewhat before the onset of psychosis), or do they reflect a brain whose early development was disrupted so as to preclude the development of normal cerebral structure and function?126, lS6 Epidemiologic
Abnormal cortical folding in high-risk individuals: a predictor of the development of schizophrenia?
Biological Psychiatry, 2004
A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether, within individuals at genetic high risk for schizophrenia, there are pre-existing differences in gyral folding between those who subsequently develop the disease and those who remain unaffected. Methods: Assessment was conducted on baseline magnetic resonance imaging scans of 30 young adults grouped into 14 who remained unaffected and 16 who subsequently developed schizophrenia. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests and volume and genetic liability correlations were conducted for each region, followed by a post hoc examination. Results: Right prefrontal lobe GI values were significantly increased in individuals who subsequently developed schizophrenia. Post hoc examination suggested that the areas of greatest increase lay anteriorly and laterally in Brodmann areas 9 and 10. Correlations with volume and analysis of covariance suggested some overlap between GI and volume measures. Conclusions: Differences in frontal lobe GI might reflect disturbed or abnormal connectivity predictive of subsequent schizophrenia.
Structural covariance and cortical reorganisation in schizophrenia: a MRI-based morphometric study
Psychological medicine, 2018
In patients with schizophrenia, distributed abnormalities are observed in grey matter volume. A recent hypothesis posits that these distributed changes are indicative of a plastic reorganisation process occurring in response to a functional defect in neuronal information transmission. We investigated the structural covariance across various brain regions in early-stage schizophrenia to determine if indeed the observed patterns of volumetric loss conform to a coordinated pattern of structural reorganisation. Structural magnetic resonance imaging scans were obtained from 40 healthy adults and 41 age, gender and parental socioeconomic status matched patients with schizophrenia. Volumes of grey matter tissue were estimated at the regional level across 90 atlas-based parcellations. Group-level structural covariance was studied using a graph theoretical framework. Patients had distributed reduction in grey matter volume, with high degree of localised covariance (clustering) compared with ...