Vol. 8, No. 1, 2002 Page 7


RESEARCH IN BRIEF: SEROTONIN

Aggression, suicide again linked to reduced serotonin activity

A recent report adds to the growing body of evidence linking low serotonin levels to aggression and suicidal behavior.

G. P. Placidi and colleagues studied 93 individuals suffering from depression, measuring their cerebrospinal fluid levels of metabolites of the neurotransmitters serotonin, dopamine, and norepinephrine. They found that higher lifetime levels of aggression were strongly correlated with lower cerebrospinal fluid levels of 5-hydroxyindolacetic acid (5- HIAA), the major metabolite of serotonin. In addition, their data showed that lower levels of 5-HIAA were found in high-lethality suicide attempters than in those who tried methods less likely to be lethal. In contrast, they say, "the dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression."

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"Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels," G. P. Placidi, M. A. Oquendo, K. M. Malone, Y. Y. Huang, S. P. Ellis, and J. J. Mann, Biological Psychiatry, Vol. 50, No. 10, November 15, 2001, 783-91. Address: G. P. Placidi, Center for the Study of Suicidal Behavior, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032.

Familial bipolar disorder: a serotonin connection?

Serotonin system abnormalities appear to play a role in familial bipolar disorder (manic depression), according to a recent study.

In a double-blind, crossover study, P. Quintin and colleagues compared 20 unaffected relatives from families with two or more bipolar members to control subjects from families with no history of the disorder. The responses of both groups were tested five hours following administration of a tryptophan-depleted drink or a placebo. Tryptophan is an amino acid that the body converts to serotonin.

The researchers found that plasma tryptophan levels dropped more in subjects from bipolar families than in other subjects following the tryptophan-depleted drink. In addition, the individuals with bipolar relatives were more likely than controls to report a negative mood following the depleted drink, and became more impulsive. The researchers say tests showed that compared to controls, the subjects with bipolar relatives also exhibited lower platelet serotonin function.

The researchers say their data "replicate and extend previous findings suggesting that unaffected relatives of patients with bipolar affective disorder are more susceptible to low tryptophan availability."

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"Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder," P. Quintin, C. Benkelfat, J. M. Launay, I. Arnulf, A. Pointereau-Bellenger, S. Barbault, J. C. Alvarez, O. Varoquaux, F. Perez- Diaz, R. Jouvent, and M. Leboyer, Biological Psychiatry, Vol. 50, No. 3, August 1, 2001, 184-90. Address: P. Quintin, Service de Psychiatrie, Hopital Albert Chenevier et Henri Mondor, AP-HP, Creteil, France.

Female aggression linked to low serotonin

Research links reduced serotonin to aggression in men, and a recent study indicates that lowered serotonin levels may also contribute to aggressive behavior in women during the premenstrual phase of their monthly cycles.

Alyson Bond et al. gave 24 premenstrual woman amino acid drinks, some containing tryptophan–an amino acid that the body converts to serotonin—and others lacking in tryptophan. Later, the women were asked to compete on a reaction time test. The women were told that they were competing against unseen opponents who could administer an annoying noise each time the women lost a round of the competition, and that they could administer a noise to the opponents in return. (In reality, there were no opponents, and the researchers administered increasing levels of noise through the headphones of the participants.)

When the women performed the task without noise provocation, both groups' reactions were similar. However, when the women performed the task under provocation (increasing levels of noise), the tryptophan-depleted women set the volume of noise delivered to the "opponent" significantly higher than did women in the control group. While all of the women had low aggression scores initially, those with the highest initial hostility scores responded the most aggressively.

Bond et al. conclude, "Decreased serotonergic neurotransmission increases aggression in women as well as men." They note that the study did not determine whether this effect is specific to the premenstrual phase.

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"Tryptophan depletion increases aggression in women during the premenstrual phase," A. J. Bond, J. Wingrove, and D. G. Critchlow, Psychopharmacology, Vol. 156, No. 4, August 2001, 477-80. Address: Alyson J. Bond, Section of Clinical Psychopharmacology, Institute of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK, a.bond@iop.kcl.ac.uk

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