Serotonin transporter loss and psychotic state in methamphetamine users

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Background : In animals, methamphetamine is known to have a neurotaxic effect on seroronin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. However, it remains unknown whether or not methamphetamine damages serotonin neurons in humans.Objective : To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent former methamphetamine abusers.Desigh : The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated in the brain using positron emission tomography (PET) and [^<11>C](+)McN-5652. A case-control analysis was performed with the estimates derived from region-of-interest (ROI) and statistical parametric mapping (SPM) methods, followed by within-case analysis with the measures of clinical variables.Setting : Partieipants were recruited from the community to a hospital research center.Participants : Twelve currently abst … More inent former methamphetamine abusers (5 women, 7 men) and age-, gender-, and twelve education-matched healthy control subjects (5 women, 7 men).Main Outcome Measures : The duration of methamphetamine use, magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [^<11>C](+)McN-5652 distribution volume.Results : The methamphetamine abusers showed increased levels of aggression compared to those of the control subjects. Both ROI and SPM analyses revealed that the serotonin transporter density in global brain regions (eg, midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in the methamphetamine abusers than in the control subjects, and this reduction was found to be significantly inversely correlated with the duration of methamphetamine use. Furthermore, SPM analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers.Conclusions : Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even among those in a currently abstinent state. Less