Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.
Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.
Amin
Zenab
Z
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA. zenab.amin@yale.edu
Gueorguieva
Ralitza
R
Cappiello
Angela
A
Czarkowski
Kathryn A
KA
Stiklus
Stephanie
S
Anderson
George M
GM
Naftolin
Frederick
F
Epperson
C Neill
CN
D000339:Affect / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D008568:Memory / Q000187:drug effects; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D013997:Time Factors; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*; D014706:Verbal Learning / Q000187:drug effects; D014796:Visual Perception / Q000187:drug effects
D006728:Hormones; D004958:Estradiol; D014364:Tryptophan