Central nervous system serotonin function and cardiovascular responses to stress.
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.
Williams
R B
RB
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA. redfordw@acpub.duke.edu
Marchuk
D A
DA
Gadde
K M
KM
Barefoot
J C
JC
Grichnik
K
K
Helms
M J
MJ
Kuhn
C M
CM
Lewis
J G
JG
Schanberg
S M
SM
Stafford-Smith
M
M
Suarez
E C
EC
Clary
G L
GL
Svenson
I K
IK
Siegler
I C
IC
D000328:Adult; D000483:Alleles; D001794:Blood Pressure; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006439:Hemodynamics; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013315:Stress, Psychological / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000503:physiopathology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid