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From the Departments of Psychiatry and Behavioral Sciences (R.B.W., J.C.B., G.L.C., K.M.G., M.J.H., I.C.S., E.C.S.), Anesthesiology (K.G., M.S.-S.), Pharmacology and Cancer Biology (C.M.K., S.M.S.), Pathology (J.G.L.), and Genetics (D.A.M., I.K.S.), Duke University Medical Center, Durham, North Carolina.
Address reprint requests to: Dr. Redford B. Williams, Box 3926, Duke University Medical Center, Durham, NC 27710. Email: redfordw{at}acpub.duke.edu
OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress.
METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing.
RESULTS: Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol.
CONCLUSIONS: These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.
Key Words: serotonin • brain • cardiovascular reactivity • stress • genes (serotonin transporter promoter polymorphism).
Abbreviations: ANOVA = analysis of variance; CNS = central nervous system; CSF = cerebrospinal fluid; CV = cardiovascular; HR = heart rate; MAP = mean arterial pressure; SES = socioeconomic; 5HIAA = 5-hydroxyindoleacetic acid; 5HTTLPR = polymorphism of the promoter region of the serotonin transporter gene.
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