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

Persistent Link:
http://hdl.handle.net/10150/610010
Title:
Number of risk genotypes is a risk factor for major depressive disorder: a case control study
Author:
Garriock, Holly; Delgado, Pedro; Kling, Mitchel; Carpenter, Linda; Burke, Michael; Burke, William; Schwartz, Thomas; Marangell, Lauren; Husain, Mustafa; Erickson, Robert; Moreno, Francisco
Affiliation:
Interdisciplinary Program in Genetics, Department of Psychiatry, University of Arizona, Tucson, AZ, USA; Department of Psychiatry, College of Medicine, The University of Arizona Health Sciences Center, 1501 N. Campbell Ave. 7-OPC, Tucson, Arizona 85724, Phone (520) 626-6509, Fax (520) 626-6050, USA; Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA; Neuroscience Center, National Institute of Mental Health, Rockville, MD, USA; Department of Psychiatry, Butler Hospital Brown University, Providence, RI, USA; Department of Psychiatry and Behavioral Sciences, Kansas University School of Medicine, Witchita, KS, USA; Department of Psychiatry, University of Nebraska Medical Center, Omaha, NE, USA; Department of Psychiatry, New York State School of Medicine, Purchase, NY, USA; Department of Psychiatry, Baylor College of Medicine, Waco, TX, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; Departments of Pediatrics and Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA
Issue Date:
2006
Publisher:
BioMed Central
Citation:
Behavioral and Brain Functions 2006, 2:24 doi:10.1186/1744-9081-2-24
Journal:
Behavioral and Brain Functions
Rights:
© 2006 Garriock et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
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.
EISSN:
1744-9081
DOI:
10.1186/1744-9081-2-24
Version:
Final published version
Additional Links:
http://www.behavioralandbrainfunctions.com/content/2/1/24

Full metadata record

DC FieldValue Language
dc.contributor.authorGarriock, Hollyen
dc.contributor.authorDelgado, Pedroen
dc.contributor.authorKling, Mitchelen
dc.contributor.authorCarpenter, Lindaen
dc.contributor.authorBurke, Michaelen
dc.contributor.authorBurke, Williamen
dc.contributor.authorSchwartz, Thomasen
dc.contributor.authorMarangell, Laurenen
dc.contributor.authorHusain, Mustafaen
dc.contributor.authorErickson, Roberten
dc.contributor.authorMoreno, Franciscoen
dc.date.accessioned2016-05-20T08:56:24Z-
dc.date.available2016-05-20T08:56:24Z-
dc.date.issued2006en
dc.identifier.citationBehavioral and Brain Functions 2006, 2:24 doi:10.1186/1744-9081-2-24en
dc.identifier.doi10.1186/1744-9081-2-24en
dc.identifier.urihttp://hdl.handle.net/10150/610010-
dc.description.abstractBACKGROUND: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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.behavioralandbrainfunctions.com/content/2/1/24en
dc.rights© 2006 Garriock et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleNumber of risk genotypes is a risk factor for major depressive disorder: a case control studyen
dc.typeArticleen
dc.identifier.eissn1744-9081en
dc.contributor.departmentInterdisciplinary Program in Genetics, Department of Psychiatry, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Psychiatry, College of Medicine, The University of Arizona Health Sciences Center, 1501 N. Campbell Ave. 7-OPC, Tucson, Arizona 85724, Phone (520) 626-6509, Fax (520) 626-6050, USAen
dc.contributor.departmentDepartment of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USAen
dc.contributor.departmentNeuroscience Center, National Institute of Mental Health, Rockville, MD, USAen
dc.contributor.departmentDepartment of Psychiatry, Butler Hospital Brown University, Providence, RI, USAen
dc.contributor.departmentDepartment of Psychiatry and Behavioral Sciences, Kansas University School of Medicine, Witchita, KS, USAen
dc.contributor.departmentDepartment of Psychiatry, University of Nebraska Medical Center, Omaha, NE, USAen
dc.contributor.departmentDepartment of Psychiatry, New York State School of Medicine, Purchase, NY, USAen
dc.contributor.departmentDepartment of Psychiatry, Baylor College of Medicine, Waco, TX, USAen
dc.contributor.departmentDepartment of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USAen
dc.contributor.departmentDepartments of Pediatrics and Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USAen
dc.identifier.journalBehavioral and Brain Functionsen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.