The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia.
Schizophrenia has been linked to abnormal dopamine function, recently to excessive amphetamine-induced release of striatal dopamine, and also to pathology of prefrontal cortical neurons. It has been hypothesized that prefrontal pathology is a primary condition that leads to dopamine dysregulation. We evaluated in vivo the relationship between neuronal integrity in dorsolateral prefrontal cortex, assessed as N-acetylaspartate (NAA) relative concentrations measured with proton magnetic resonance spectroscopic imaging, and amphetamine-induced release of striatal dopamine, assessed with 11C-raclopride Positron Emission Tomography (PET) in patients with schizophrenia and in healthy subjects. In the patients, NAA measures in dorsolateral prefrontal cortex selectively predicted striatal displacement of 11C-raclopride after amphetamine infusions (rho = -0.76, p < .02). In contrast, NAA measures in other cortical regions and in healthy subjects did not show any correlation. These results support the hypothesis that in schizophrenia neuronal pathology of dorsolateral prefrontal cortex is directly related to abnormal subcortical dopamine function.
Bertolino
A
A
Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Breier
A
A
Callicott
J H
JH
Adler
C
C
Mattay
V S
VS
Shapiro
M
M
Frank
J A
JA
Pickar
D
D
Weinberger
D R
DR
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D020891:Raclopride / Q000493:pharmacokinetics; D012016:Reference Values; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods
D002250:Carbon Radioisotopes; D001224:Aspartic Acid; D020891:Raclopride; C000179:N-acetylaspartate; D000661:Amphetamine; D004298:Dopamine