Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.
OBJECTIVE
A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics.


METHODS
PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score.


RESULTS
The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms.


CONCLUSIONS
These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.
Sekine
Y
Y
Department of Psychiatry and Neurology, Hamamatsu School of Medicine, 3600 Handa-cho Hamamatsu, 431-3192 Shizuoka, Japan. ysekine@hama-med.ac.jp
Iyo
M
M
Ouchi
Y
Y
Matsunaga
T
T
Tsukada
H
H
Okada
H
H
Yoshikawa
E
E
Futatsubashi
M
M
Takei
N
N
Mori
N
N
D000328:Adult; D016739:Behavior, Addictive / Q000175:diagnosis; D001923:Brain Chemistry / Q000187:drug effects; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis*; D002421:Caudate Nucleus / Q000737:chemistry / Q000000981:diagnostic imaging; D002525:Cerebellar Cortex / Q000737:chemistry / Q000000981:diagnostic imaging; D003042:Cocaine / Q000031:analogs & derivatives*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000737:chemistry / Q000000981:diagnostic imaging; D017397:Prefrontal Cortex / Q000737:chemistry / Q000000981:diagnostic imaging; D011605:Psychoses, Substance-Induced / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism; D011699:Putamen / Q000737:chemistry / Q000000981:diagnostic imaging; D019966:Substance-Related Disorders / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008694:Methamphetamine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine