Lower dopamine transporter binding potential in striatum during depression.
Previous studies suggest that there is a dopamine lowering process during major depressive episodes (MDE). To investigate this, we measured the dopamine transporter binding potential (DAT BP) in the striatum of depressed and healthy subjects using [(11)C]RTI-32 PET. The DAT, a predominantly presynaptic receptor, decreases in density after chronic dopamine depletion and the BP is proportional to receptor density. In all striatal regions, subjects with MDE had significantly lower DAT BP. Low striatal DAT BP in MDE is consistent with a downregulation of DAT in response to a dopamine lowering process. There was also a strong, highly significant, inverse correlation between striatal DAT BP and neuropsychological tests of dopamine-implicated symptoms in patients (i.e. patients with lower DAT BP performed better). Lower DAT BP itself reduces extracellular clearance of dopamine. Patients who did not decrease their striatal DAT BP failed to compensate for low dopamine and showed greater impairment on dopamine related tests.
Meyer
J H
JH
PET Imaging Centre, and Mood Division, Centre for Addiction and Mental Health, Department of Psychiatry and University of Toronto, 250 College St., Toronto, Ont. M5T1R8, Canada.
Krüger
S
S
Wilson
A A
AA
Christensen
B K
BK
Goulding
V S
VS
Schaffer
A
A
Minifie
C
C
Houle
S
S
Hussey
D
D
Kennedy
S H
SH
D000293:Adolescent; D000328:Adult; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000031:analogs & derivatives*; D003342:Corpus Striatum / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009483:Neuropsychological Tests; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C067730:RTI-COC 32; D003042:Cocaine