TY - JOUR
T1 - Lithium's antisuicidal efficacy
T2 - Elucidation of neurobiological targets using endophenotype strategies
AU - Kovacsics, Colleen E.
AU - Gottesman, Irving I.
AU - Gould, Todd D.
PY - 2009
Y1 - 2009
N2 - Lithium used as a drug treatment for major mental disorders such as bipolar disorder and depression is effective in reducing the risk of both attempted and completed suicide. However, the mechanisms underlying lithium's antisuicidal actions are not yet known, limiting the development of novel lithium-mimetic compounds that may help reduce suicide risk with fewer undesirable side effects. Suicide is a complex behavior, complicated to study in humans, and impossible to fully reproduce in animal models. The endophenotype approach, by which quantitative measures of neurobiological function are used to assess and subclassify psychiatric illness, may present a path to new discoveries. Aggression and impulsivity are candidate endophenotypes strongly associated with suicide; we review the evidence supporting aggression and impulsivity as suicide endophenotypes, as well as the effects of lithium on these constructs in both humans and rodents. Examining the mechanisms that contribute to lithium's antiaggressive and antiimpulsive effects may assist in understanding how lithium acts to reduce the risk of suicide and in elucidating the neurobiological underpinnings of suicidal behavior.
AB - Lithium used as a drug treatment for major mental disorders such as bipolar disorder and depression is effective in reducing the risk of both attempted and completed suicide. However, the mechanisms underlying lithium's antisuicidal actions are not yet known, limiting the development of novel lithium-mimetic compounds that may help reduce suicide risk with fewer undesirable side effects. Suicide is a complex behavior, complicated to study in humans, and impossible to fully reproduce in animal models. The endophenotype approach, by which quantitative measures of neurobiological function are used to assess and subclassify psychiatric illness, may present a path to new discoveries. Aggression and impulsivity are candidate endophenotypes strongly associated with suicide; we review the evidence supporting aggression and impulsivity as suicide endophenotypes, as well as the effects of lithium on these constructs in both humans and rodents. Examining the mechanisms that contribute to lithium's antiaggressive and antiimpulsive effects may assist in understanding how lithium acts to reduce the risk of suicide and in elucidating the neurobiological underpinnings of suicidal behavior.
KW - Aggression
KW - Impulsivity
KW - Mood stabilizer
KW - Personality traits
KW - Pharmacotherapy
KW - Suicidal behavior
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U2 - 10.1146/annurev.pharmtox.011008.145557
DO - 10.1146/annurev.pharmtox.011008.145557
M3 - Review article
C2 - 18834309
AN - SCOPUS:65249098306
SN - 0362-1642
VL - 49
SP - 175
EP - 198
JO - Annual review of pharmacology and toxicology
JF - Annual review of pharmacology and toxicology
ER -