Our Serotonin, Our Selves? - Page 7


Uncovering the Underlying Causes of Suicide

In seeking the biological basis for suicidal impulsivity, Mann and Arango's work has increasingly focused on the presence of serotonin, or lack thereof, in certain parts of the brain, particularly the prefrontal cortex. Serotonin seems to exert a calming influence on the mind in ways that aren't completely understood. Thus the presence of serotonin, in the right place and the right time, might make a person more balanced and less impulsive.

Arango and Mann reviewed studies from the 1960s that found that the brains of patients who killed themselves contained abnormally low levels of serotonin and its major breakdown product, the metabolite 5-hydroxyindoleacetic acid (5-HIAA). The studies also found that in only half of these suicides did the patients suffer from depression—the other half had diagnoses of schizophrenia, alcoholism, and personality disorders.

Because these early researchers were investigating the causes and effects of depression, their study of suicides was abandoned at this stage. But a succession of later studies in the 1970s showed that patients with low levels of 5-HIAA in their spinal fluid made a greater number of serious or lethal suicide attempts. What Mann and Arango gleaned from this earlier work was that the decrease in serotonin and 5-HIAA didn't relate to the patient's psychiatric diagnosis or method of death, but instead related solely to their committing suicide—the link was between decreased serotonin and suicide, not diagnosis.

The next step for the team was to develop a method of examining serotonin activity at the cellular level. Through years of trial and error, they found a method of performing several different biochemical tests on the same brain slice and ascertaining the exact anatomical locations of the variations between the samples they're evaluating. The slices then were reassembled virtually, using special software, allowing Mann and Arango to produce an overall model of how those abnormalities might operate together to influence behavior.

With their new tools, they've found further differences between the brains of people who commit suicide and those who don't. For instance, the neurotransmitter acetylcholine may be implicated in suicidal behavior, while the brain chemical norepinephrine has probably been ruled out as an influencing factor.

Recently Arango has uncovered a further, illuminating discrepancy among the brains of those who choose to kill themselves: the brains of suicide subjects have about one-third fewer presynaptic serotonin transporters and about one-third more postsynaptic serotonin receptors. Arango believes this indicates that the brains of suicide subjects are desperately trying to compensate for the low serotonin levels, attempting to "make the most of every molecule of serotonin they have" by increasing the molecular equipment that senses the neurotransmitter. Clearly, though, the brain's compensatory mechanisms or the use of antidepressants aren't always enough. As she says, "They can be so sick, Prozac can't help them."

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