Studies show that up to 95 per cent of suicides occur in patients with a history of psychiatric illness at the time of death. However, the majority of patients with depression or schizophrenia never attempt suicide. Nor is there a link between the objective severity of a psychiatric illness and the likelihood of suicide.
This observation led researchers to examine factors within the individual that predispose them to a suicidal tendency. Twenty-five years ago, the first clue suggesting that there might be a biological component to a person's threshold for a suicidal act emerged.
Post-mortem studies of the brain and spinal fluid of patients who had committed suicide found that the levels of a brain neurotransmitter called serotonin were reduced, regardless of the person's exact psychiatric diagnosis.
Serotonin is manufactured at the base of the brain, and the cells carrying the neurotransmitter project from the brain stem to the frontal cortex of the brain. The frontal cortex is the part of the central nervous system closely associated with mood regulation, decision making and executive reasoning ("will I? won't I? should I? shouldn't I?").
So, the finding that the frontal cortex was low in serotonin and that there were alterations in the receptors for serotonin in this area of the brains of suicide victims led biological suicide researchers to suggest that serotonin could be closely involved with critical reasoning and decision making. In other words, a person prone to suicide did not have adequate levels of the brain chemical needed to resist a suicidal impulse.
Dr Kevin Malone, consultant psychiatrist at the Mater Hospital and senior lecturer in adult psychiatry at University College Dublin, was involved in some of the 16 major studies which support this link when he worked at Columbia University in New York during the 1990s.
Since then, he says "my scientific mission is to translate biological post-mortem findings into live patients at risk of suicide so that we can deliver more accurate and specific intervention therapies".
Dr Malone has recently published research which he carried out in the US, using brain-imaging studies to detect serotonin receptor levels. By injecting a seroton-in-releasing agent, the brain image of patients who had made serious suicide attempts "lit up" to a lesser degree than those who had a low suicidal tendency, confirming reduced serotonin levels in those prone to suicide.
Along with colleagues in the Mater and UCD, he is now planning follow-up research using a sophisticated MRI scanner, customised software and a non-invasive psychological trigger of serotonin release.
If the trials are successful, Dr Malone says we could have a method of biologically identifying those people at high risk of suicide in the next five years. Such patients could be offered life-long maintenance antidepressant therapy aimed at increasing the level of serotonin within the brain cells. Eventually, it should be possible to develop specific antidepressants for suicidal patients, in the same way that certain antibiotics are reserved for the treatment of resistant infections. Maintenance psychological therapies are also an important preventive strategy.
A trigger-threshold model for suicidal acts has been proposed by Dr Malone and an American colleague Dr J. J. Mann. In this model, a vulnerable individual with a low threshold for committing suicide is triggered into the suicide act by an outside stress. Typical stressors include acute psychiatric illness, acute alcohol and drug use, medical illness and family or social stresses. This ties in with the biological explanation which suggests that a person with low serotonin neurotransmitter function has a low threshold for suppressing the suicidal thoughts brought on by the outside stress.
There is additional scientific evidence to support a biological explanation for suicide.
Genetic: The regulation of serotonin levels is at least partially under genetic influence. There is evidence that an atypical gene can influence suicidal behaviour. The gene for tryptophan hydroxylase, an enzyme which regulates serotonin, is altered in patients who have attempted suicide. The Department of Psychiatry in the Mater Hospital/UCD, along with the Dublin Molecular Centre and the Conway Institute, are planning detailed research into the disease-susceptibility genes associated with suicidal depression.
Alcohol and substance abuse: Alcohol reduces the transportation of serotonin within the prefrontal cortex as well as destroying serotonin cells in the brain stem. This destruction of these inhibiting brain pathways may be particularly relevant to the recent increase in suicide amongst young Irish males which has occurred alongside a rise in youth alcohol consumption. The abuse of ecstasy and other drugs could have a similar biological role.
Early life experience: Abuse in childhood has been associated with a higher rate of suicidal behaviour in adults. Although no link with serotonin activity had yet been proved in humans, animal models have shown that monkeys deprived of maternal rearing have lower serotonin activity.
Diet and hormones: Fatty acids, which are derived from cholesterol are essential to maintain nerve-cell architecture. Low levels of cholesterol have been shown to decrease serotonin activity in non-human experiments. A link has been shown in humans between low cholesterol and increased impulsivity but not with suicide itself. "There is some preliminary evidence that cholesterol and fatty acids may have a contributing role to play in the regulation of mood and impulsivity," Dr Malone says. The jury is also out on the relationship between oestrogen levels, mood and suicidal behaviour, while elevated levels of the stress hormone cortisol have been linked with a reduction in neurotransmitters in animals.
Will the body of evidence for the biological and non-chemical model for suicide bring about better treatments? Dr Malone points to recent research showing that the latest generation of antidepressants - the serotonin selective reuptake inhibitors (SSRIs) - are more suicide protective than older antidepressants. A separate study showed that depressed alcoholics treated with Fluoxetine (an SSRI) had reduced suicide rates. Lithium has now been shown to have an anti-suicidal effect in patients with bipolar disorder (manic depression). And those suffering from schizophrenia, treated with a new generation anti-psychotic drug called Clozapine, have reduced suicidal feelings.
Not alone is there a definite biological explanation for suicide, but there is even reason to believe that the next decade will bring new and more specific treatments for people at risk.