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

Tyrone D. Cannon, Paul M. Thompson, Theo G.M. Van Erp, Arthur W. Toga, Veli Pekka Poutanen, Matti Huttunen, Jouko Lonnqvist, Carl Gustav Standerskjold-Nordenstam, Katherine L. Narr, Mohammad Khaledy, Chris I. Zoumalan, Rajneesh Dail, Jaakko Kaprio

Research output: Contribution to journalArticlepeer-review

265 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3228-3233
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number5
DOIs
StatePublished - 5 Mar 2002
Externally publishedYes

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