Lower central serotonergic responsivity is associated with preclinical carotid artery atherosclerosis.
OBJECTIVE
Central nervous system serotonergic neurotransmission appears to play a role in mood disorders, eating habits, and sleep, and also modulates blood pressure and metabolism. This investigation tested a hypothesized association between central serotonergic functioning and preclinical atherosclerosis.


METHODS
Subjects were 244 adults 30 to 55 years of age and free of clinically evident vascular disease (52% men, 84% white). Central serotonergic responsivity was measured as the rise in serum prolactin concentration (area under the curve) over 2.5 hours, adjusted for baseline prolactin, after citalopram administered intravenously at 0.33 mg/kg lean body weight. Carotid artery morphology served as a marker of preclinical atherosclerosis, and carotid artery intima-media thickness and plaque occurrence were determined by B-mode ultrasonography.


RESULTS
In linear regression models including age, gender, race, and citalopram concentration, a 1 SD lower prolactin response was associated with greater maximum intima-media thickness (+0.016 mm; P=0.006) and with greater mean intima-media thickness (+0.009 mm; P=0.03). The odds ratio for carotid artery plaque corresponding to a 1 SD decrease in prolactin response, adjusted for age, race, sex, and citalopram concentration, was 1.47 (95% CI, 0.98 to 2.19; P=0.06). The metabolic syndrome mediated (P<0.01), but did not fully account for, the association between lower prolactin response and greater maximum intima-media thickness.


CONCLUSIONS
In this young and relatively healthy sample, blunted prolactin response to citalopram was associated with carotid artery thickening, suggesting that individual differences in central serotonergic responsivity are inversely related to preclinical vascular disease.
Muldoon
Matthew F
MF
Center for Clinical Pharmacology, University of Pittsburgh, Pittsburgh, PA 15260, USA. mfm10@pitt.edu
Mackey
Rachel H
RH
Sutton-Tyrrell
Kim
K
Flory
Janine D
JD
Pollock
Bruce G
BG
Manuck
Stephen B
SB
D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers; D001786:Blood Glucose; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D015283:Citalopram; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors; D014463:Ultrasonography
D015415:Biomarkers; D001786:Blood Glucose; D015283:Citalopram; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors