MONOAMINE SYSTEMS IN ALCOHOLISM AND SUICIDE

血清素能和其他单胺能系统出现变化

Alterations in the serotonergic and other monoaminergic systems appear to be associated with alcoholism. Alcoholics are at a significantly higher risk for suicide than the general population. Altered serotonergic function is associated with suicide and serious suicide attempts. The present study will use an integrated psychosocial and neurobiological approach to elucidate the relationship of brain monoamine systems to alcoholism and suicidal behavior in order to determine if biological changes associated with alcoholism are the same as, or similar to, those seen with suicide and may therefore explain the high rate of suicide among alcoholics. An alternative hypothesis is that the biological changes associated with suicide risk also predispose toward the development of alcoholism. Over a 5 year period, 18 suicides and 18 nonsuicides, meeting DSM-III-R criteria for alcohol dependence, and 18 nonpsychiatric controls, all matched, will be systematically investigated with regard to psychosocial and neurobiological indices. In addition, 9 acutely intoxicated nonalcoholic suicides and 9 acutely intoxicated nonalcoholic controls will be investigated using the same indices to assess the acute effects of alcohol. The controls will be matched to the suicides on the basis of postmortem interval, age, side of brain used for biochemical analyses, sex and season of death. Cases with positive toxicological screens (from peripheral fluids or brain), for illicit of psychoactive drugs, with the exception of alcohol, will be excluded from the study. A psychosocial profile and DSM-III-R diagnosis will be obtained by a psychological autopsy involving interviews with key informants. A neurobiological profile will be obtained by measuring indices of monoaminergic systems in postmortem brain tissue. (1) The serotonergic system will be assessed by: (a) measuring levels of tryptophan, 5-HT and its metabolite 5-HIAA in specified brain regions; (b) radioligand binding in membrane preparations to 5-HT(1A), 5-HT transporter and 5-HT(2) sites to establish binding indices of specific 5-HT receptor subtypes; and (c) parallel autoradiographic studies to measure the same receptor sites; (2) The adrenergic and noradrenergic systems will be studied by measuring: (a) levels of NE and MHPG in specified brain regions; (b) binding indices in membrane preparations to study beta 1-adrenergic receptors; and (c) quantitative receptor autoradiography of high- and low-affinity beta 2-adrenergic receptors; alpha 1- and alpha 2-adrenergic receptors. (3) Additionally, levels of dopamine and a metabolite homovanillic acid will be measured in specified brain regions. Specific biochemical correlates of alcohol dependence, suicide or acute alcohol effects are hypothesized. The findings of this study will have theoretical importance as well as suggest new pharmacological approaches.