Number of risk genotypes is a risk factor for major depressive disorder: a case control study

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Issue Date
2007-10-31Author
Holly Garriock
Pedro Delgado
Mitchel Kling
Linda Carpenter
Michael Burke
William Burke
Thomas Schwartz
Lauren Marangell
Mustafa Husain
Robert Erickson
Francisco Moreno
Publisher
BioMedCentral
Type
Article
Published Version
http://www.behavioralandbrainfunctions.com/content/2/1/24Version
http://www.biomedcentral.com/content/pdf/1744-9081-2-24.pdf
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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BACKGROUND:The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects.METHODS:A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies.RESULTS:A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group.CONCLUSION:An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder.
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Holly Garriock;Pedro Delgado;Mitchel Kling;Linda Carpenter;Michael Burke;William Burke;Thomas Schwartz;Lauren Marangell;Mustafa Husain;Robert Erickson;Francisco Moreno: Number of risk genotypes is a risk factor for major depressive disorder: a case control study. Behavioral and Brain Functions 2006, 2(1):24.
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Except where otherwise noted, this item's license is described as: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.