Central nervous system serotonin function and cardiovascular responses to stress

Objective: The objective of this study was to evaluate the impact of indice s of central nervous system (CNS) serotonin function on cardiovascular reac tivity to mental stress. Methods: Lumbar puncture was performed on 54 healt hy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hy droxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respe ct to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. Results: P ersons with one or two long [I) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons wi th the s/s 5HTTLPR genotype. Persons with one or two 1 alleles or higher CS F 5HIAA levels also exhibited greater blood pressure and heart rate respons es to a mental stress protocol. Conclusions: These findings suggest the 5HT TLPR polymorphism affects CNS serotonin function, and they are consistent w ith the general hypothesis that CNS serotonin function is involved in the r egulation of potentially health-damaging biobehavioral characteristics. In particular, the I allele could contribute, through its association with inc reased cardiovascular reactivity to stress, to increased risk of cardiovasc ular disease.