A polygenic theory of schizophrenia.

Gottesman, Irving I.; Shields, James

doi:10.1073/pnas.58.1.199

Cited by 545 publications

(146 citation statements)

References 9 publications

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“…It is assumed that for most individuals with this disorder, the genetic liability for schizophrenia is due to the interaction of risk alleles for multiple genes, rather than a single genetic defect (Gottesman and Shields 1967). Two recent meta-analyses of genome-wide scans have identified multiple loci of particular significance (Badner and Gershon 2002;Lewis et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex

Colantuoni

Hyde²,

Mitkus³

et al. 2008

Brain Struct Funct

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The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. All microarray data are available at NCBI's Gene Expression Omnibus: GEO Series accession number GSE11546 (http://www.ncbi.nlm.nih.gov/geo) [corrected]

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Section: Introductionmentioning

confidence: 99%

Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex

Colantuoni

Hyde²,

Mitkus³

et al. 2008

Brain Struct Funct

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show abstract

“…There has been early evidence that the Mendelian gene model does not fit psychiatric disorders, and polygenic models have been discussed for about 40 years now (see Gottesman and Shields 1967). ''Nonetheless, there is continued hope that advances in psychiatric genetics and particularly the identification of individual susceptibility genes will alter, in fundamental ways, our approach to psychiatric diagnosis'' (Kendler 2006(Kendler , p. 1142.…”

Section: Complex Gene Concepts and Consequences For A Concept Of Mentmentioning

confidence: 96%

“…The methodical and methodological problems of linkage and association studies led to the rise of a concept which was introduced for schizophrenia by Gottesman and Shields in 1967, the endophenotype. The term is used to describe ''internal phenotypes discoverable by a 'biochemical test or microscopic examination''' (Gottesman and Gould 2005, p. 65).…”

Section: Endophenotypes and The Gene-environment Approachmentioning

confidence: 99%

The concept of the gene in psychiatric genetics and its consequences for the concept of mental illness

Lux

2008

Poiesis Prax

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“…The mode of inheritance is complex like cancer, diabetes and heart diseases and it involves interaction among multiple genes and environmental factors (Risch 1990). In this polygenic model, multiple risk genes of small effect are acting additively or multiplicatively (Gottesman and Shields 1967). Because non-genetic etiological factors are obscure, genetic investigations may hold the key to understanding etiology.…”

Section: Geneticsmentioning

confidence: 99%

An Update on the Epidemiology of Schizophrenia with a Special Reference to Clinically Important Risk Factors

El-Missiry

Aboraya

Manseur

et al. 2009

Int J Ment Health Addiction

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Schizophrenia is a chronic mental illness which poses a tremendous burden on the families, caregivers and the society. The purpose of this paper is to provide an updated review of the epidemiology of schizophrenia with a special attention to the clinically important risk factors such as drug abuse, hormonal factors and the new advances in genetic research. The authors reviewed the literature with a special focus to the recent papers published from January 1970 to present. The prevalence of schizophrenia varied by ten-fold and the incidence of schizophrenia varied by five-fold among different studies. Significant advances in genetic research and DNA technology have been achieved over the past two decades and suggested substantial genetic etiology of schizophrenia. Extensive studies have been done with many variations in the prevalence, incidence and risk factors of schizophrenia among different studies.

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A polygenic theory of schizophrenia.

Cited by 545 publications

References 9 publications

Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex

Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex

The concept of the gene in psychiatric genetics and its consequences for the concept of mental illness

An Update on the Epidemiology of Schizophrenia with a Special Reference to Clinically Important Risk Factors

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