Regional Gray Matter, White Matter, and Cerebrospinal Fluid Distributions in Schizophrenic Patients, Their Siblings, and Controls

Cannon, Tyrone D.; Erp, Theo G.M. van; Huttunen, Matti; Lönnqvist, Jouko; Salonen, Oili; Valanne, Leena; Poutanen, Veli-Pekka; Standertskjöld-Nordenstam, Carl-Gustav; Gur, Raquel E.; Yan, Michelle

doi:10.1001/archpsyc.55.12.1084

Cited by 238 publications

(150 citation statements)

References 34 publications

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“…Since the time of Kraepelin, the nonpsychotic relatives of schizophrenics have often been noted to manifest quantitative abnormalities in personality. 31,32 These findings were later extended to other 'endophenotypes', such as cognition, 33,34 psychophysiology, 35,36 and brain structure 37,38 that are thought to be related to the expression of genes relevant to the etiology of schizophrenia (reviewed by Siever and Davis 39 ).…”

Section: The Effects Of Genes In Nonpsychotic Relativesmentioning

confidence: 99%

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

2004

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Section: The Effects Of Genes In Nonpsychotic Relativesmentioning

confidence: 99%

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

2004

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“…Magnetic resonance imaging (MRI) studies in unaffected family members (FM) of schizophrenia patients suggest that genetic factors affect brain structure (1)(2)(3)(4)(5), with FM generally showing characteristics of brain structure in-between patients and healthy controls (HC). Likewise, high risk individuals such as patient offsprings with no clinical history of psychosis, have similar structural abnormalities, most notably in hippocampus and amygdala, with some contradictory results (6-9) having being reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

Unaffected Family Members and Schizophrenia Patients Share Brain Structure Patterns: A High-Dimensional Pattern Classification Study

Fan

Gur²,

Gur³

et al. 2008

Biological Psychiatry

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111

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Background-A number of studies have provided evidence for genetic modulation of brain structure in unaffected family members of schizophrenia patients (FM), using conventional regionof-interest volumetric analysis. High-dimensional pattern analysis and classification methods have been reported recently to have the capacity to determine subtle and spatially complex structural patterns that distinguish schizophrenia patients from healthy controls, using standard magnetic resonance imaging (MRI). This study investigates whether such endophenotypic patterns are found in FM via similar computer-based image analysis approaches.Correspond to: Christos Davatzikos, Professor, Department of Radiology, University of Pennsylvania, 3600 Market street, Suite 380, Philadelphia, PA 19104, Tel: 215-349-8587, Fax: 215-614-0266, E-Mail: christos@rad.upenn.edu. Financial Disclosures: There are no conflicts of interest including any financial, personal or other relationships with people or organizations, by any of the co-authors, related to the work described in the paper.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMethods-A high-dimensional pattern classifier was constructed from a group of 69 patients and 79 healthy controls, via an analysis that identified a subtle, and spatially complex and distributed pattern of reduced brain volumes. Patients were distinguished from healthy controls with sensitivity of 92.9% and specificity 89.8%, using jackknife method. Then the constructed classifier was applied to examine brain structure of 30 FM.Results-The classifier indicated that family members had structural profiles highly overlapping with those of patients. Moreover, an orbitofrontal region of relatively increased white matter was found to contribute significantly to the classification, indicating that white matter alterations, along with reductions of gray matter volumes, might be present in patients and unaffected family members.Conclusions-These findings give evidence that high-dimensional pattern analysis and classification can identify complex and subtle structural endophenotypes that are shared by probands and their unaffected family members.

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“…Several such studies have found that frontal and temporal lobe regions may be particularly affected (4,5,16,17). Whether this regional pattern reflects differential involvement of specific cytoarchitectonic areas remains to be determined but potentially could be resolved by voxel-based morphometric analysis (18,19).…”

mentioning

confidence: 99%

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia

Cannon

Thompson

Erp

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The symptoms of schizophrenia imply disruption to brain systems supporting higher-order cognitive activity, but whether these systems are impacted differentially against a background of diffuse cortical gray-matter deficit remains ambiguous. Some unaffected first-degree relatives of schizophrenics also manifest cortical gray-matter deficits, but it is unclear whether these changes are isomorphic with those in patients, and the answer is critical to understanding the neurobiological conditions necessary for disease expression given a predisposing genotype. Here we report three-dimensional cortical surface maps (probabilistic atlases matching subjects' anatomy point by point throughout cortex) in monozygotic (MZ) and dizygotic (DZ) twins discordant for chronic schizophrenia along with demographically matched control twins. A map encoding the average differences between schizophrenia patients and their unaffected MZ co-twins revealed deficits primarily in dorsolateral prefrontal cortex, superior temporal gyrus, and superior parietal lobule. A map encoding variation associated with genetic proximity to a patient (MZ co-twins > DZ co-twins > control twins) isolated deficits primarily in polar and dorsolateral prefrontal cortex. In each case, the statistical significance was confirmed through analysis of 10,000 Monte Carlo permutations, and the remaining cortex was shown to be significantly less affected by contrast analysis. The disease-related deficits in gray matter were correlated with measures of symptom severity and cognitive dysfunction but not with duration of illness or antipsychotic drug treatment. Genetic and disease-specific influences thus affect gray matter in partially nonoverlapping areas of predominantly heteromodal association cortex, changes that may act synergistically in producing overt behavioral features of the disorder.

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Regional Gray Matter, White Matter, and Cerebrospinal Fluid Distributions in Schizophrenic Patients, Their Siblings, and Controls

Abstract: Background: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their sources have not been established conclusively.

Cited by 238 publications

References 34 publications

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

Unaffected Family Members and Schizophrenia Patients Share Brain Structure Patterns: A High-Dimensional Pattern Classification Study

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia

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