The proposed study is an integrated psychosocial and neurobiologic approach to the problem of youthful suicide. Over a four year period, 20 suicide victims, aged 13-19 and 20 matched controls dying of accidents, homicides or sudden natural deaths will be systematically investigated with regard to both neurobiological and psychosocial indices. The controls will be matched to the suicides on age, sex, Tanner Stage, postmortem interval, season of death, and side of the brain (left versus right) studied. Cases with positive brain, blood, or urine toxicologies for illicit or psychotropic drugs or alcohol will be excluded from this study. A psychosocial profile on each subject will be developed by use of psychological autopsy interviews with key informants targeting: (a) Axis I and II disorders, current and lifetime; (b) history of impulsive violence, and (c) family history of Axis I and II disorders, impulsive violence, and suicidality. A neurobiological profile of youthful suicide victims will be developed through serotonergic and other probes using postmortem brain material of victims and controls. (1) The serotonergic system will be assessed by measuring: (a) absolute levels of serotonin (5- HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific brain regions; (b) 5-HT1A, paroxetine, and 5-HT2 binding indices in the above-noted brain regions; and (c) parallel autoradiographic studies related to (b). (2) Additionally, (a) regional levels of norepinephrine (NE), dopamine (DA), and homovanillic acid (HVA) will be assayed, as well as (b) binding for low- and high-affinity beta-adrenergic receptors by quantitative receptor autoradiography. It is predicted that: (1) youthful suicide victims, compared to psychopathological and normal controls, will show decreased 3H-paroxetine, increased 5-HT2, and increased beta-adrenergic binding in the prefrontal cortex; (2) differences between suicides and controls will cut across Axis I psychiatric diagnoses; and (3) changes in serotonergic function will be correlated with history of impulsive violence, Axis II personality disorder and family history of Axis II disorder, impulsive violence, and suicidal behavior.
|Underwood, Mark D; Mann, J John; Arango, Victoria (2007) Morphometry of dorsal raphe nucleus serotonergic neurons in alcoholism. Alcohol Clin Exp Res 31:837-45|
|Arango, V; Underwood, M D; Gubbi, A V et al. (1995) Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 688:121-33|