Levels of homovanillic acid and 5hydroxyindoleacetic acid in cerebrospinal fluid

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Suicide attempts represent a more varied type of behaviour than completed suicides, yet neurobiological studies of suicide attempters have shown a remarkable consistency in pointing to a serotonergic dysfunction. In a meta-analysis, which included 20 research reports, Lester (15) concluded that there is strong evidence of decreased cerebrospinal fluid levels of 5-HIAA in subjects who had previously made a suicide attempt compared to diagnostically matched non-attempters. Moreover, in three out of five studies, low cerebrospinal-fluid 5-HIAA was also able to predict future suicidal behaviour in subjects with depression or schizophrenia. Lester did not, however, find enough evidence to substantiate a relationship between suicide attempt status and the levels of homovanillic acid or 3-methoxy-4-hydroxphenylglycol (MHPG), a metabolite of noradrenaline, in cerebrospinal fluid.

Nordstrom et al.(16> found that the risk of completed suicide within 1 year after a suicide attempt was 2.5 times greater in those depressed patients whose cerebrospinal fluid level of 5-HIAA was in the lower half of the group.

The association between lowered 5-HIAA cerebrospinal fluid levels and suicidality has not been convincingly shown for bipolar disorder, but it does hold for people with unipolar depression, schizophrenia, and those with personality disorders. It therefore appears to represent a biochemical marker for suicidality, and is largely independent of diagnosis.(2)

Not all depressed people who attempt suicide have low 5-HIAA cerebrospinal fluid levels, however, raising the question as to whether there are biologically defined subtypes of suicide attempters. We found that 5-HIAA was lower in depressed subjects who made the most serious suicide attempts, i.e. those attempts that were planned and resulted in the highest lethality.(2)

These findings are consistent with both human and animal studies that show an association between low cerebrospinal fluid levels of 5-HIAA and greater lifetime aggressivity and impulsivity. Thus, low serotonergic activity is associated with both suicidal acts and externally directed aggression.

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