Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies

Studies of neurotransmitter metabolites in cerebrospinal fluid (CSF) were initially focused on depressive illness. Although several studies have demonstrated low concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid (HVA), in depressed patients, these early studies may have been biased by concomitant administration of antidepressant drugs (which tend to lower CSF 5-HIAA), amount of CSF drawn (there is a concentration gradient for both metabolites), and selection of control subjects. Once these methodological details are controlled for, the differences between depressed patients and controls are unimpressive. However, there is a remarkably consistent association between low concentrations of CSF 5-HIAA and suicidal behavior, as evidenced by over 20 studies. The association is not confined to depressive illness but has also been found in schizophrenia, personality disorder, and certain impulse control disorders (but, interestingly, not in bipolar disorder). A low concentration of CSF 5-HIAA in a suicide attempter is associated with a substantial increase in short-term suicide risk. CSF studies in violent criminals, and in nonhuman primates, suggest that aggression dyscontrol may partly explain the association between suicide and serotonin, which is of considerable theoretical interest. CSF 5-HIAA determinations may also be helpful in the clinical assessment of suicide risk.