Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging

Mental Health Clinical Research Center, Iowa City, IA 52242-1057.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/1995; 272(22):1763-9. DOI: 10.1001/jama.272.22.1763
Source: PubMed


To determine general and regional indices of structural brain abnormality in schizophrenia.
Case-control comparison study.
Fifty-two patients diagnosed as having schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, were compared with 90 healthy volunteers recruited from the community.
Structural brain images were acquired using magnetic resonance; measurements were obtained using three-dimensional visualization of volume-rendered brains and an automated atlas-based dissection of specific regions. General measures included the volume of total brain tissue, total cerebrospinal fluid (CSF), and CSF within the ventricular system. Regional measures included the volume of tissue and CSF in the frontal, temporal, parietal, and occipital lobes and the cerebellum.
Compared with the controls, the patients had a smaller average volume of total brain tissue and a greater average volume of total and ventricular CSF. A specific relative decrease in brain tissue was found only in the frontal lobes, although the volume of CSF was greater in patients than in controls in all brain regions.
In addition to the generalized brain abnormalities observed in schizophrenia, a regional abnormality may be present in frontal regions. Since the frontal lobes integrate multimodality information and perform a variety of "higher" cognitive and emotional functions that are impaired in schizophrenia, the frontal abnormality noted is consistent with the clinical presentation of the illness. Impaired frontal function and a disruption in its complex circuitry (including thalamocortical projections) may explain why patients with schizophrenia often have significant deficits in formulating concepts and organizing their thinking and behavior.

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    • "Furthermore , metabolic activity in the frontal cortex has been associated with power deficits in schizophrenia (Alper et al., 1998). Neuroimaging investigations show functional and anatomical deficits particularly in the dorsolateral prefrontal cortex (DLPFC) (Andreasen et al., 1994; Sullivan et al., 1998; Radhu et al., 2015), a region also reported to have altered thalamic excitatory inputs in schizophrenia (Glantz et al., 2000). "
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    ABSTRACT: Deficits in both resting alpha-range (8-12Hz) electroencephalogram (EEG) activity and steady state evoked potential (SSVEP) responses have been reported in schizophrenia. However, the topographic specificity of these effects, the relationship between resting EEG and SSVEP, as well as the impact of antipsychotic medication on these effects, have not been clearly delineated. The present study sought to address these questions with 256 channel high-density EEG recordings in a group of 13 schizophrenia patients, 13 healthy controls, and 10 non-schizophrenia patients with psychiatric diagnoses currently taking antipsychotic medication. At rest, the schizophrenia group demonstrated decreased alpha EEG power in frontal and occipital areas relative to healthy controls. With SSVEP stimulation centered in the alpha band (10Hz), but not with stimulation above (15Hz) or below (7Hz) this range, the occipital deficit in alpha power was partially reverted. However, the frontal deficit persisted and contributed to a significantly reduced topographic relationship between occipital and frontal alpha activity for resting EEG and 10Hz SSVEP alpha power in schizophrenia patients. No significant differences were observed between healthy and medicated controls or between medicated controls and schizophrenia. These findings suggest a potential intrinsic deficit in frontal eyes-closed EEG alpha oscillations in schizophrenia, whereby potent visual stimulation centered in that frequency range results in an increase in the occipital alpha power of these patients, which however does not extend to frontal regions. Future research to evaluate the cortical and subcortical mechanisms of these effects is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 07/2015; 168(1). DOI:10.1016/j.schres.2015.06.012 · 3.92 Impact Factor
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    • "The higher thalamic white-to-gray ratio detected by SBM confirmed the evidence detected by the VBM analysis. The smaller cuneus and lingual gyrus angle agree with the lesser occipital lobe gray matter reported by others [35] and abnormalities in fornix and cingulum are also consistent with previous studies [36, 37]. Our findings suggested that the posterior thalamic projection which penetrates the retrolenticular part of internal capsule and connects to the occipital lobe through cingulum was abnormal in patients. "
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    ABSTRACT: We present a feature extraction method to emphasize the interrelationship between gray and white matter and identify tissue distribution abnormalities in schizophrenia. This approach utilizes novel features called structural phase and magnitude images. The phase image indicates the relative contribution of gray and white matter, and the magnitude image reflects the overall tissue concentration. Three different analyses are applied to the phase and magnitude images obtained from 120 healthy controls and 120 schizophrenia patients. First, a single-subject subtraction analysis is computed for an initial evaluation. Second, we analyze the extracted features using voxel based morphometry (VBM) to detect voxelwise group differences. Third, source based morphometry (SBM) analysis was used to determine abnormalities in structural networks that co-vary in a similar way. Six networks were identified showing significantly lower white-to-gray matter in schizophrenia, including thalamus, right precentral-postcentral, left pre/post-central, parietal, right cuneus-frontal, and left cuneus-frontal sources. Interestingly, some networks look similar to functional patterns, such as sensory-motor and vision. Our findings demonstrate that structural phase and magnitude images can naturally and efficiently summarize the associated relationship between gray and white matter. Our approach has wide applicability for studying tissue distribution differences in the healthy and diseased brain.
    Neurology Research International 01/2012; 2012(9):735249. DOI:10.1155/2012/735249
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    • "Full scale IQ scores were derived from the Wechsler Adult Intelligence Scale – Revised Edition (WAIS-R). Based on a priori theoretical considerations (Green et al., 2004; Hill, Schuepbach, Herbener, Keshavan, & Sweeney, 2004; Kareken et al., 1995; Milev, Ho, Arndt, & Andreasen, 2005; Saykin et al., 1994), 40 test variables from the standardized neuropsychological battery were grouped into 6 cognitive domains: Verbal Memory, Processing Speed/Attention, Problem Solving, Language, Visuospatial Abilities and Motor Skills. These cognitive domain groupings had good internal consistency (Median Cronbach's alpha=0.80; "
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    ABSTRACT: Marijuana exposure during the critical period of adolescent brain maturation may disrupt neuro-modulatory influences of endocannabinoids and increase schizophrenia susceptibility. Cannabinoid receptor 1 (CB1/CNR1) is the principal brain receptor mediating marijuana effects. No study to-date has systematically investigated the impact of CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse. We genotyped 235 schizophrenia patients using 12 tag single nucleotide polymorphisms (tSNPs) that account for most of CB1 coding region genetic variability. Patients underwent a high-resolution anatomic brain magnetic resonance scan and cognitive assessment. Almost a quarter of the sample met DSM marijuana abuse (14%) or dependence (8%) criteria. Effects of CNR1 tSNPs and marijuana abuse/dependence on brain volumes and neurocognition were assessed using ANCOVA, including co-morbid alcohol/non-marijuana illicit drug misuse as covariates. Significant main effects of CNR1 tSNPs (rs7766029, rs12720071, and rs9450898) were found in white matter (WM) volumes. Patients with marijuana abuse/dependence had smaller fronto-temporal WM volumes than patients without heavy marijuana use. More interestingly, there were significant rs12720071 genotype-by-marijuana use interaction effects on WM volumes and neurocognitive impairment; suggestive of gene-environment interactions for conferring phenotypic abnormalities in schizophrenia. In this comprehensive evaluation of genetic variants distributed across the CB1 locus, CNR1 genetic polymorphisms were associated with WM brain volume variation among schizophrenia patients. Our findings suggest that heavy cannabis use in the context of specific CNR1 genotypes may contribute to greater WM volume deficits and cognitive impairment, which could in turn increase schizophrenia risk.
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