Post-mortem studies document alterations in the central noradrenergic system in suicide. However, studies of non-fatal suicide attempts have, thus far, found no consistent relationship to the
noradrenaline metabolite 3-methoxy-4-hydroxphenylglycol (
MHPG) in cerebrospinal fluid (CSF). We therefore conducted a prospective study of CSF
MHPG and suicidal acts in major depression and
bipolar depression. CSF
MHPG was assayed in 184
drug-free patients with DSM-IV
major depressive disorder or
bipolar disorder, presenting for treatment of a current depressive episode, who were then followed-up for up to 12 months. Survival analysis was conducted using Cox proportional hazards modelling to test association of CSF
MHPG and future suicidal behaviour, and potential clinical mediators. Twenty-seven individuals made a suicide attempt (two fatal) in the follow-up period. Lower CSF
MHPG predicted future suicide attempt or suicide (22% increase in hazard for each 10 pmol/ml lower
MHPG, p=0.045). Lower CSF
MHPG also correlated with higher medical lethality of future suicidal act (mean
MHPG: 49+/-18 vs. 32+/-12 pmol/ml for low- vs. high-lethality, t=2.8, d.f.=25, p=0.009). Smoking and self-rated depression severity were also associated with lower CSF
MHPG and with future suicide attempt, but were not statistically significant mediators in multivariate models. In conclusion, lower CSF
MHPG is associated with short-term risk for future suicidal behaviour in the 12 months following a major depressive episode. Psychopathology that mediates the relationship between lower CSF
MHPG and future suicidal behaviour needs to be identified.