Candidate endophenotypes for genetic studies of suicidal behavior.
Twin, adoption, and family studies have established the heritability of suicide attempts and suicide. Identifying specific suicide diathesis-related genes has proven more difficult. As with psychiatric disorders in general, methodological difficulties include complexity of the phenotype for suicidal behavior and distinguishing suicide diathesis-related genes from genes associated with mood disorders and other suicide-associated psychiatric illness. Adopting an endophenotype approach involving identification of genes associated with heritable intermediate phenotypes, including biological and/or behavioral markers more proximal to genes, is an approach being used for other psychiatric disorders. Therefore, a workshop convened by the American Foundation for Suicide Prevention, the Department of Psychiatry at Columbia University, and the National Institute of Mental Health sought to identify potential target endophenotypes for genetic studies of suicidal behavior. The most promising endophenotypes were trait aggression/impulsivity, early-onset major depression, neurocognitive function, and cortisol social stress response. Other candidate endophenotypes requiring further investigation include serotonergic neurotransmission, second messenger systems, and borderline personality disorder traits.
Mann
J John
JJ
Department of Psychiatry, NewYork State Psychiatric Institute/ColumbiaUniversity, 1051 Riverside Drive, New York, NY 10032, USA. jjm@columbia.edu
Arango
Victoria A
VA
Avenevoli
Shelli
S
Brent
David A
DA
Champagne
Frances A
FA
Clayton
Paula
P
Currier
Dianne
D
Dougherty
Donald M
DM
Haghighi
Fatemah
F
Hodge
Susan E
SE
Kleinman
Joel
J
Lehner
Thomas
T
McMahon
Francis
F
Mościcki
Eve K
EK
Oquendo
Maria A
MA
Pandey
Ganshayam N
GN
Pearson
Jane
J
Stanley
Barbara
B
Terwilliger
Joseph
J
Wenzel
Amy
A
D000374:Aggression; D001883:Borderline Personality Disorder / Q000235:genetics; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007175:Impulsive Behavior / Q000235:genetics; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D015290:Second Messenger Systems; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D013406:Suicide, Attempted / Q000517:prevention & control; D000092864:Suicide Prevention
D012701:Serotonin; D006854:Hydrocortisone