Estradiol and progesterone modify the effects of the serotonin reuptake transporter polymorphism on serotonergic responsivity to citalopram

• Type of Material: Article
• Authors: Vasiliki J. Michopoulos, Emory University; Sarah L. Berga, Emory University; Mark Wilson, Emory University
• Language: English
• Date: 2011-12
• Publisher: American Psychological Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2013 American Psychological Association
• Title of Journal or Parent Work: Experimental and Clinical Psychopharmacology
• ISSN: 1064-1297
• Volume: 19
• Issue: 6
• Start Page: 401
• End Page: 408
• Grant/Funding Information: The study was supported by NIH grants HD46501 and RR00165, and F31MH085445 (VM).
• Keywords: citalopram; serotonin transporter; estradiol; females; progesterone
• Research Categories: Psychology, Cognitive

Abstract

Individual vulnerability to psychopathologies is linked to a number of genetic polymorphisms including the serotonin transporter (5HTT) promoter polymorphic region (5HTTLPR). A single copy of the short variant (s-variant) allele of 5HTTLPR confers increased susceptibility to anxiety disorders and depression and decreased efficacy of serotonin-releasing agents in pharmacotherapy compared to the homozygous long 5HTTLPR variant (l/l). The data suggesting that the 5HTTLPR polymorphism modulates the efficacy of serotonin-releasing agents in pharmacotherapy is inconsistent. Other factors such as age, gender, and hormonal status could interact with 5HTTLPR genotype to affect individual physiological and behavioral responses to serotonin reuptake inhibitors such as citalopram. Indeed, estradiol and progesterone, the primary female steroid hormones, exert an array of effects on the serotonergic system, including 5HTT expression. The present study used ovariectomized female rhesus monkeys to determine the interaction between the 5HTTLPR polymorphism and the effects of mid-follicular levels of estradiol and luteal levels of progesterone on serotonergic responsivity to acute citalopram administration. The increase in serum prolactin, a surrogate measure of serotonin activity, following citalopram administration was significantly larger in l/l females than in s-variant females over the course of two hours during concurrent estradiol and progesterone hormone replacement only. These data suggest that ovarian function and the 5HTTLPR polymorphism interact to gate serotonergic reactivity in females, suggesting that clinicians should be aware of the ovarian status and 5HTTLPR genotype of women when considering serotonergic pharmacotherapy in women.