However, there are non-psychiatric sources of variability in serotonin level, and few of the serotonin studies take them into account (i.e., statistically control for them) in all subject categories used. In particular, serotonin (actually 5-HIAAA, its main break-down product) measured at the lumbar level through spinal tap is lower in males, goes up with age, and declines with stature. (Serotonin diffuses out of the brain into the cerebrospinal fluid. From there, most of it is transported to the bloodstream; the fraction making it down as far as the lumbar region decreases with increasing spinal length).

Using those studies in the set of 39 that provided information on height, age, and sex of normal controls, Balaban computed the effects of those variables alone on serotonin level. These values were then used to adjust the measured serotonin levels in all studies for all subject categories for which mean height and age and male-female ratio were published. Because the three subject categories happened to consistently differ in these traits, correcting for these non-psychiatric determinants of serotonin level yields results that are quite different from what is typically reported: violent psychiatric patients do indeed have somewhat lower levels than normal controls, but so do the non-violent psychiatric and neurological patients, and the psychiatric groups do not differ from each other. In short, people with a history of being in an institution or under psychiatric or neurological treatment have lower levels of serotonin than normal nonpatients.

In addition to the reasons adduced above for questioning the usefulness of low serotonin as a marker for impulsive aggression, there are reports in the scientific literature that, while far from refuting the claim that low serotonin increases impulsive aggression, contradict it and thus warrant weighing in the balance. These are not simply studies that fail to find a relationship between low serotonin and aggression—unless the relationship were extremely strong in a statistical sense, one would expect a certain number of studies to come up empty by chance even if the relationship were generally valid. One kind of contradictory finding is the observation in at least two studies that highly aggressive children evince not a reduction but an increase in serotonin function (Castellanos et al. 1994; Halperin et al. 1994). And there is the much-cited discovery in a large Dutch family of an association between a genetic deficiency of the enzyme MAOA and impulsive violent behavior (Brunner et al. 1993). What has gone unremarked on in the discussion of this finding (which, predictably, was heralded in the non-technical media as the revelation of a "gene for aggression") is the problem it poses for the other major putative organic cause of abnormal aggression, serotonin. For MAOA is the enzyme that, among other functions, breaks down serotonin, which means that the affected men in this group would, arguably, have an excessively high level of serotonin. And, finally, the same primate experiments mentioned earlier, which showed that altering serotonin level affects behavior, also provide evidence that serotonin is equally a result of behavior. If the dominant male is removed from a group of vervet monkeys, an aggressive contest for dominance results. The male that ascends to top rank will experience an increase in serotonin level, and the exiled alpha male, if not returned to its group, will undergo a serotonin drop (McGuire and Troisi 1998). To the extent that it is legitimate to extrapolate to humans, this observation calls into question the assumption that serotonin abnormality precedes the behavioral problems with which it has been linked.

The correct inference from all of the foregoing is not that anyone low on the serotonin scale should be a dangerous, depressed, and overweight compulsive gambler, torn between shyness and nymphomania, who would be kept awake at night by their headaches and restless legs even if they didn't suffer from insomnia. It is rather that serotonin is not a very discriminating marker for violence and that the neurophysiological and neurochemical characteristics that accompany low serotonin—whether as causes, consequences, or both—are not limited to brain regions that govern aggression.

But what if there were no ambiguity about the serotonin-aggression relationship? If it were clearly established that underactive serotonin circuits increased the risk for serious aggressive behavior, and only that risk, what insight would be gained into human violence? Would it help us understand the shocking increase in youth homicide in the United States beginning in the middle 1980s or the decrease of recent years? Would it clarify why the rate of violent crime has declined in New York, Los Angeles, and Tampa but increased in New Orleans and Richmond, why Nevada's murder rate is 10 times higher than South Dakota's, or why the U.S. rate is 15 times higher than Britain's?

The explanation of these facts will come not from research in neurobiology but from understanding economic forces, variation in cultural mores regarding the acceptability of violence, diversity in the kinds and efficacy of means of informal and formal social control, and availability of firearms. A reasonable response to this assertion would be to suggest that individual differences in serotonin could explain why this person rather than the next succumbs to the distinctive mix of violence-promoting influences impinging on a given neighborhood, ethnic group, class, or nation. I am rather pessimistic about the potential of this approach, however. But that may just be the serotonin talking.

References

Balaban, E., J. S. Alper, and Y. L. Kasamon. 1996. Mean genes and the biology of aggression: A critical review of recent animal and human research. J. Neurogenetics 11: 1-43.

Brunner, H. G., M. Nelen, X. O. Breakefield, H. H. Ropers, and B. A. van Oost. 1993. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262: 578-80.

Castellanos, F. X., J. Elia, M. J. Kruesi, C. S. Gulotta, I. N. Mefford, W. Z. Potter, G. F. Ritchie, and J. L. Rapopor. 1994. Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder. Psychiatry Research 52: 305-16.

Halperin, J. M., V. Sharma, L. J. Siever, S. T. Schwartz, K. Matier, G. Wornell, and J. H. Newcorn. 1994. Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder. Am J Psychiatry 151: 243-8.

McGuire, M. and A. Troisi. 1998. Darwinian Psychiatry. New York: Oxford University.

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