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Am J Psychiatry 160:636-645, April 2003
© 2003 American Psychiatric Association


Reviews and Overviews

The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

Irving I. Gottesman, Ph.D., Hon. F.R.C.Psych., and Todd D. Gould, M.D.

Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward—and successful—genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.




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Am. J. PsychiatryHome page
L. Menzies, G. B. Williams, S. R. Chamberlain, C. Ooi, N. Fineberg, J. Suckling, B. J. Sahakian, T. W. Robbins, and E. T. Bullmore
White Matter Abnormalities in Patients With Obsessive-Compulsive Disorder and Their First-Degree Relatives
Am J Psychiatry, October 1, 2008; 165(10): 1308 - 1315.
[Abstract] [Full Text] [PDF]


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Am. J. PsychiatryHome page
L. Almasy, R. C. Gur, K. Haack, S. A. Cole, M. E. Calkins, J. M. Peralta, E. Hare, K. Prasad, M. F. Pogue-Geile, V. Nimgaonkar, et al.
A Genome Screen for Quantitative Trait Loci Influencing Schizophrenia and Neurocognitive Phenotypes
Am J Psychiatry, September 1, 2008; 165(9): 1185 - 1192.
[Abstract] [Full Text] [PDF]


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Arch Gen PsychiatryHome page
E. J. C. G. van den Oord, P.-H. Kuo, A. M. Hartmann, B. T. Webb, H.-J. Moller, J. M. Hettema, I. Giegling, J. Bukszar, and D. Rujescu
Genomewide Association Analysis Followed by a Replication Study Implicates a Novel Candidate Gene for Neuroticism
Arch Gen Psychiatry, September 1, 2008; 65(9): 1062 - 1071.
[Abstract] [Full Text] [PDF]


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Alcohol AlcoholHome page
C. A. Hodgkinson, Q. Yuan, K. Xu, P.-H. Shen, E. Heinz, E. A. Lobos, E. B. Binder, J. Cubells, C. L. Ehlers, J. Gelernter, et al.
Addictions Biology: Haplotype-Based Analysis for 130 Candidate Genes on a Single Array
Alcohol Alcohol., September 1, 2008; 43(5): 505 - 515.
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Schizophr BullHome page
W. P. Horan, J. J. Blanchard, L. A. Clark, and M. F. Green
Affective Traits in Schizophrenia and Schizotypy
Schizophr Bull, September 1, 2008; 34(5): 856 - 874.
[Abstract] [Full Text] [PDF]


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ScienceHome page
S. R. Chamberlain, L. Menzies, A. Hampshire, J. Suckling, N. A. Fineberg, N. del Campo, M. Aitken, K. Craig, A. M. Owen, E. T. Bullmore, et al.
Orbitofrontal Dysfunction in Patients with Obsessive-Compulsive Disorder and Their Unaffected Relatives
Science, July 18, 2008; 321(5887): 421 - 422.
[Abstract] [Full Text] [PDF]


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FocusHome page
E. Leibenluft and B. A. Rich
Pediatric Bipolar Disorder
Focus, July 1, 2008; 6(3): 331 - 347.
[Abstract] [Full Text] [PDF]


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Schizophr BullHome page
K. M. Prasad and M. S. Keshavan
Structural Cerebral Variations as Useful Endophenotypes in Schizophrenia: Do They Help Construct "Extended Endophenotypes"?
Schizophr Bull, July 1, 2008; 34(4): 774 - 790.
[Abstract] [Full Text] [PDF]


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Schizophr BullHome page
S. K. Hill, M. S. H. Harris, E. S. Herbener, M. Pavuluri, and J. A. Sweeney
Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder
Schizophr Bull, July 1, 2008; 34(4): 743 - 759.
[Abstract] [Full Text] [PDF]


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Schizophr BullHome page
S. Heckers
Making Progress in Schizophrenia Research
Schizophr Bull, July 1, 2008; 34(4): 591 - 594.
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Schizophr BullHome page
G. K. Thaker
Neurophysiological Endophenotypes Across Bipolar and Schizophrenia Psychosis
Schizophr Bull, July 1, 2008; 34(4): 760 - 773.
[Abstract] [Full Text] [PDF]


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Schizophr BullHome page
P.-I Lin and B. D. Mitchell
Approaches for Unraveling the Joint Genetic Determinants of Schizophrenia and Bipolar Disorder
Schizophr Bull, July 1, 2008; 34(4): 791 - 797.
[Abstract] [Full Text] [PDF]


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Schizophr BullHome page
G. Thaker
Psychosis Endophenotypes in Schizophrenia and Bipolar Disorder
Schizophr Bull, July 1, 2008; 34(4): 720 - 721.
[Abstract] [Full Text] [PDF]


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Am. J. PsychiatryHome page
M. Rietschel, L. Beckmann, J. Strohmaier, A. Georgi, A. Karpushova, F. Schirmbeck, K. V. Boesshenz, C. Schmal, C. Burger, R. A. Jamra, et al.
G72 and Its Association With Major Depression and Neuroticism in Large Population-Based Groups From Germany
Am J Psychiatry, June 1, 2008; 165(6): 753 - 762.
[Abstract] [Full Text] [PDF]




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