Peet, Eloise
(2005)
Association of the 5-HTTLPR with Prolactin Response to Citalopram in a Community Population.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
ASSOCIATION OF THE 5-HTTLPR WITHPROLACTIN RESPONSE TO CITALOPRAMIN A COMMUNITY POPULATIONEloise Peet, BSUniversity of Pittsburgh, 2004The 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.
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| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
2 February 2005 |
| Date Type: |
Completion |
| Defense Date: |
30 November 2004 |
| Approval Date: |
2 February 2005 |
| Submission Date: |
10 December 2004 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Neuroscience |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
5-HTTLPR; Citalopram; serotonin transporter |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-12102004-101814/, etd-12102004-101814 |
| Date Deposited: |
10 Nov 2011 20:10 |
| Last Modified: |
15 Nov 2016 13:54 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10272 |
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