ASSOCIATION OF THE 5-HTTLPR WITH
PROLACTIN RESPONSE TO CITALOPRAM
IN A COMMUNITY POPULATION
Eloise Peet, BS
University of Pittsburgh, 2004
The serotonin transporter (5-HTT) is a key mechanism regulating magnitude and duration of serotonergic transmission in the central nervous system, and is the site of action of selective serotonin reuptake inhibitors (SSRIs) used for treating psychiatric conditions. Variation in treatment response to SSRIs has been correlated with a common bi-allelic length polymorphism in the 5-HTT-promoter region (5-HTTLPR), known to modulate transcriptional efficiency of the 5-HTT gene in vitro. The alleles, designated long (l) or short (s), result in one of three possible genotypes: l/l, l/s, or s/s. The (s) allele has been hypothesized to have a dominant functional effect, and has been associated with decreased transporter transcription efficiency and poorer therapeutic response to antidepressants. Acute transporter blockade with SSRIs rapidly increases central nervous system serotonin levels, leading to hypothalamic receptor stimulation and the release of several hormones, including prolactin. The specific aim of this study is to characterize the prolactin response to acute 5-HTT-reuptake blockade according to 5-HTTLPR genotype, to further elucidate the effect of this polymorphism on serotonin transporter function in vivo. This study has been designed to test the hypothesis that, when compared to subjects with the l/l genotype, subjects with either the s/l or s/s genotype will experience a blunted prolactin response following acute administration of the highly selective reuptake inhibitor Citalopram. To accomplish this goal, a cohort of 206 community volunteers were intravenously administered a weight-adjusted dose of Citalopram. Each subject was genotyped for the 5-HTTLPR, and blood samples were obtained for prolactin and Citalopram levels immediately before and at regular intervals for 2.5 hours after the Citalopram injection. Results: Citalopram-induced prolactin response, reported as prolactin area under the curve (PRL AUC), was significantly associated with 5-HTTLPR (F = 3.08, p = 0.048). Among individuals with the s/s genotype, PRL AUC response (M±SD: 84.2 ± 51.8 ng/ml * 150min) was significantly lower (p = 0.014) than the l/l group (246.0 ± 40.2 ng/ml * 150 min). The difference in PRL AUC between subjects with the l/l genotype and the l/s group (172.5 ± 41.3 ng/ml * 150 min) was not significant (p = 0.21); the difference in PRL AUC between subjects with the l/s genotype and the s/s group also was not significant (p = 0.23). When results were analyzed as the maximum change in prolactin, the Citalopram-induced PRL MAX was similarly associated with 5-HTTLPR (p = 0.034). Conclusions: Subjects with the 5-HTTLPR s/s genotype exhibit significantly lower prolactin response in response to the SSRI Citalopram than subjects carrying two copies of the l allele. The s allele does not have a dominant effect on the prolactin response to Citalopram in a non-patient population.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12102004-101814 |
| Date | 02 February 2005 |
| Creators | Peet, Eloise |
| Contributors | Alan F. Sved, J. Patrick Card, Stephen B. Manuck |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-12102004-101814/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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