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.
