Paul Thompson's Research Publications

Cortex Mapping Reveals Regionally Specific Patterns of Genetic and Disease-Specific Gray-Matter Deficits in Twins Discordant for Schizophrenia

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Proceedings of the National Academy of Sciences of the USA, vol. 99, no. 5: 3228-3233, February 26, 2002.

1Tyrone D. Cannon PhD, 2Paul M. Thompson PhD, 1Theo van Erp, 2Arthur W. Toga PhD,
3Veli-Pekka Poutanen, 4Matti Huttunen, 4Jouko Lönnqvist, 3Carl-Gustaf Standertskjöld-Nordenstam, 2Katherine L. Narr, 2Mohammad Khaledy, 2Chris I. Zoumalan, 2Rajneesh Dail, 5Jaakko Kaprio


1Departments of Psychology, Psychiatry, and Human Genetics, UCLA
2Laboratory of Neuro Imaging, Brain Mapping Division, Department of Neurology, UCLA School of Medicine
3Department of Radiology, University of Helsinki
4Department of Mental Health and Alcohol Research, National Public Health Institute of Finland
55Department of Public Health, Universities of Helsinki and Oulu


Mapping Genetic Liability for Schizophrenia


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.


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    Paul Thompson, Ph.D.
    Assistant Professor of Neurology
    4238 Reed Neurology
    UCLA School of Medicine
    710 Westwood Plaza
    Westwood, Los Angeles CA 90095-1769, USA.

  • E-mail: thompson@loni.ucla.edu
  • Tel: (310)206-2101
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