Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.
BACKGROUND
In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether 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 methamphetamine abusers.


METHODS
Case-control analysis.


METHODS
A hospital research center.


METHODS
Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community.


METHODS
The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables.


METHODS
The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume.


RESULTS
Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping 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 in currently abstinent abusers.
Sekine
Yoshimoto
Y
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan. ysekine@hama-med.ac.jp
Ouchi
Yasuomi
Y
Takei
Nori
N
Yoshikawa
Etsuji
E
Nakamura
Kazuhiko
K
Futatsubashi
Masami
M
Okada
Hiroyuki
H
Minabe
Yoshio
Y
Suzuki
Katsuaki
K
Iwata
Yasuhide
Y
Tsuchiya
Kenji J
KJ
Tsukada
Hideo
H
Iyo
Masaomi
M
Mori
Norio
N
D000328:Adult; D000374:Aggression / Q000523:psychology*; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007546:Isoquinolines; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D008694:Methamphetamine; C058079:McN 5652