Background. Many reports have appeared on associations between platelet monoamine oxidase
(MAO) activity and susceptibility to psychiatric conditions; principally alcohol dependence but also
conduct disorder, other drug use and depression. Recently, it has become apparent that MAO
activity is inhibited by some component of cigarette smoke, and smokers have low platelet MAO
activity. Since the prevalence of smoking is higher in many of the conditions in which MAO has
been implicated, the MAO susceptibility associations may be partly, or entirely, false.
Methods. We have measured platelet MAO in 1551 subjects, recruited from the Australian
NHMRC Twin Registry, who have provided information on alcohol use and dependence, smoking,
conduct disorder, depression, attempted suicide, panic disorder and social phobia.
Results. Current smoking reduced platelet MAO activity in a significant and dose-related manner,
with no evidence of lower MAO in ex-smokers or in non-smoking subjects with co-twins who
smoked. Alcohol use and lifetime DSM-III-R alcohol dependence history were not associated with
MAO activity when smoking was taken into account. Depression, panic disorder and social phobia
showed no significant associations with platelet MAO activity. Subjects with a history of serious
attempts at suicide had low platelet MAO activity; but although the difference from controls was
as great as the reduction associated with smoking it was not significant after correction for smoking
Conclusions. Although synaptic MAO activity undoubtedly plays a role in psychopathology, the
concept that platelet MAO activity is a direct genetic marker of vulnerability to alcohol dependence
cannot be sustained.