Cited by 138Treatment of Major DepressionSuicide and Self-Harm StudiesGenetic Associations and Epidemiology

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Association of FKBP5 Polymorphisms With Suicidal Events in the Treatment of Resistant Depression in Adolescents (TORDIA) Study

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Brent, David, Melhem, Nadine, Ferrell, Robert, Emslie, Graham, Wagner, Karen Dineen, Ryan, Neal, Vitiello, Benedetto, Birmaher, Boris, Mayes, Taryn, Zelazny, Jamie, Onorato, Matthew, Devlin, Bernie, Clarke, Greg, DeBar, Lynn, Keller, Marty·2010·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2009.09040576PMC PMC2887294

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Abstract

OBJECTIVE: The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents. METHOD: A subsample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures. RESULTS: No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91). CONCLUSIONS: The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment.

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Authors: Brent, D., Melhem, N., Ferrell, R., Emslie, G., Wagner, K. D., Ryan, N., Vitiello, B., Birmaher, B., Mayes, T., Zelazny, J., Onorato, M., Devlin, B., Clarke, G., DeBar, L., & Keller, M.
Affiliations: Suburban Hospital (US)
ORCID: Brent, David
Melhem, Nadine
Emslie, Graham
Ryan, Neal
Vitiello, Benedetto
Birmaher, Boris
Mayes, Taryn
Zelazny, Jamie
Onorato, Matthew
Devlin, Bernie
DeBar, Lynn
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2010-02-01
Volume: 167
Issue: 2
Pages: 190-197
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2009.09040576
PMC: PMC2887294
OpenAlex: W2144565283
Cited by: 138
References: 38
Citations by year: 2026: 3 · 2025: 8 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 12 · 2015: 10 · 2014: 14 · 2013: 9 · 2012: 16
FWCI: 10.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders: National Institute of Mental Health (MH61958, K01MH077930, U01MH061856, MH-66371, U01MH061835, U01MH061869, MH-61869, U01MH062014, MH61856, K01MH77930, MH-61835, MH61864, U01MH061958, P30MH066371, U01MH061864, MH62014)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: FKBP5, suicidal behavior, treatment-resistant depression, adolescents, single nucleotide polymorphisms, rs1360780, hypothalamic-pituitary-adrenal axis, candidate genes, antidepressant response, venlafaxine, cognitive behavioral therapy
MeSH terms: Venlafaxine Hydrochloride, Tacrolimus Binding Protein 5, Adolescent, Cyclohexanols, Depressive Disorder, Female, Genotype, Humans, Male, Polymorphism, Genetic, Suicide, Suicide, Attempted, Cognitive Behavioral Therapy, Logistic Models, Treatment Failure, Selective Serotonin Reuptake Inhibitors, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins

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Association of FKBP5 Polymorphisms With Suicidal Events in the Treatment of Resistant Depression in Adolescents (TORDIA) Study

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