Alterations in brain serotonin synthesis in male alcoholics measured using positron emission tomography.
BACKGROUND
A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release.


METHODS
The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer alpha-[(11)C]-methyl-L-tryptophan.


RESULTS
Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala.


CONCLUSIONS
Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation.
Nishikawa
Masami
M
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Diksic
Mirko
M
Sakai
Yojiro
Y
Kumano
Hiroaki
H
Charney
Dara
D
Palacios-Boix
Jorge
J
Negrete
Juan
J
Gill
Kathryn
K
D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000031:analogs & derivatives
D019275:Radiopharmaceuticals; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan