The link between decreased serotonin function and propensity for suicide is tenuous, and still wants for a direct psychological and physiological explanation.

The idea that neurotransmitters may be involved in psychological disorders first came about in the 1950's when the similarity between LSD and serotonin was recognized. The clinical similarity between hallucinogenic symptoms of drug use and schizophrenia led scientists to hypothesise a role of serotonin in schizophrenia pathology. The concurrent discovery of psychotropic drugs allowed scientists to explore the relationship between behavior and neurochemistry. The next decade saw the emergence of the monoamine theory of depression which thought that low levels of monoamine neurotransmitters such as serotonin and noradrenaline caused depression. This concept is now known to be overly simplistic, but for many years it was the motivation for intensive research into the affect of serotonin on all types of behavior.

A study conducted on post-mortem suicide victims looked for levels of serotonin, noradrenaline, dopamine and metabolites of serotonin including 5-HIAA. The most convincing correlations were depleted levels of serotonin in the brain stem (raphe nuclei) and the hypothalamus (subcortical nuclei). No strong pattern was observed in levels of the other neurotransmitters. It was noted that factors such as drug and alcohol abuse complicated the interpretation because their complex effects on serotonin production.

Followup studies on the relation between serotonin and depression depended on assays for serotonin metabolites in cerebrospinal fluid of living patients. These studies surprisingly found a very weak correlation between behavioral depression and serotonin levels, in direct contradiction to the monoamine theory of depression.

The link between serotonin and suicide only began to be understood when it was realized that serotonin levels correlated more strongly with impulsive and compulsive behavior (see the story of Phineas Gage). People with severe personality disorders, of which high impulsivity is a common symptom, also have depleted levels of serotonin and metabolites.

Thus the relationship between low serotonin levels and suicide appears to be more one of behavioral impulsivity instead of depression. People with personality disorders often exhibit violent behavior. Committing a murder is one the risk factors correlated most strongly with suicide. The correlation between suicide and serotonin holds most strongly for violent suicide attempts.

As with both physiological and psychological theories, it is often difficult to make exact models due to the multiple causes and effects associated with each problem. Serotonin interacts with numerous receptors and controls many other functions including sleep and digestion. Suicide is nearly impossible to predict and while low serotonin levels may be common in suicide victims, the number of people with similarly low levels of serotonin who do commit suicide is very, very small. As a result, serotonin neurochemistry alone is insufficient for tagging potential suicides.