Serotonergic and noradrenergic neurobiology of alcoholic suicide.
BACKGROUND
Alcoholism is associated with alterations in the serotonergic and noradrenergic systems. Alcoholics are at a significantly higher risk for suicide than the general population. Altered serotonin (5-HT) function is associated with suicide and serious suicide attempts. We hypothesized patterns of abnormality associated independently with suicide and with alcoholism.


METHODS
Quantitative autoradiographic experiments were performed in human postmortem brain tissue sections from alcoholics, alcoholic-suicide decedents, nonalcoholic suicide decedents, and normal controls diagnosed by psychological autopsy.


RESULTS
Binding to 5-HT1A receptors is lower in both alcoholic suicides and alcoholic nonsuicides, suggesting that this effect is related to alcoholism and not suicide. In nonalcoholic suicides, there is a localized increase in 5-HT1A binding in ventral prefrontal cortex, hypothesized to be a response to less serotonin input. Therefore, alcoholic suicides may fail to up-regulate ventral prefrontal 5-HT1A receptors in response to decreased serotonergic transmission, failing to mitigate the impact of less serotonin upon signal transduction and thereby increasing the risk of suicidal behavior. Binding to the serotonin transporter is low in alcoholic suicides but not in alcoholic nonsuicides, suggesting an association with suicide, as nonalcoholic suicides also have decreased binding compared with controls. Evidence of impaired serotonergic innervation associated with alcoholism is also manifested by less 5-HT1D terminal autoreceptor binding in alcoholics. Nonalcoholic suicides do not have lower 5-HT1D binding. In the noradrenergic system, alcoholics (suicide and nonsuicide) and nonalcoholic suicide victims all have fewer pigmented locus ceruleus neurons compared with controls, yet beta1-adrenergic binding is low in both alcoholic groups, whereas alpha1-and alpha2-adrenergic binding decreases are more pronounced in the alcoholic suicide group. These noradrenergic findings differ from those in nonalcoholic suicides, which have a common feature with alcoholics in having less alpha2-and beta1-adrenergic binding but more alpha1-adrenergic binding in ventrolateral and orbital cortex.


CONCLUSIONS
Extensive but different abnormalities in both the serotonergic and noradrenergic systems have been identified in alcoholics and suicides, suggesting two separate patterns: one related to alcoholism and the other related to suicide. The different patterns suggest different causes and homeostatic responses for alcoholism and suicide.
Underwood
Mark D
MD
Department of Psychiatry, Columbia College of Physicians & Surgeons, New York, New York, USA. undie@neuron.cpmc.columbia.edu
Mann
J John
JJ
Arango
Victoria
V
D000328:Adult; D000437:Alcoholism / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012720:Severity of Illness Index; D013405:Suicide
D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin