title: Ovarian cycle effects on immediate reward selection bias in humans: a role for estradiol.
abstract: A variety of evidence suggests that, among humans, the individual tendency to choose immediate rewards ("Now") over larger, delayed rewards ("Later"), or Now bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle effects on Now bias, and whether any such effects are E+ mediated. To do so, we quantified Now/Later choice behavior in naturally cycling adult females (n = 87; ages 18-40 years) during both the menstrual phase (MP; cycle day 1-2; low E+), and the follicular phase (FP; cycle day 11-12; high E+). Now bias decreased an average of 3.6% from MP to FP (p = 0.006). Measures of salivary E+ levels at each visit were available in a subsample of participants (n = 34). Participants with a verified E+ rise from MP to FP showed significantly greater decreases in Now bias at mid-cycle (n = 23) than those without a rise (n = 11; p = 0.03); Now bias decreased an average of 10.2% in the E+ rise group but increased an average of 7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely correlated with the change in E+ (ρ = -0.39; p = 0.023), an effect driven by individuals with putatively lower frontal DA based on genotype at the Val(158)Met polymorphism in the COMT gene. This is the first demonstration that intertemporal choice varies across the ovarian cycle, with Now bias declining at mid-cycle, when fertility peaks. Moreover, our data suggest that the interacting effects of estradiol and frontal DA mediate this cycle effect on decision making.
authors.affiliation: Neurobiology Curriculum, Department of Psychology, and Biomedical Research Imaging Center, and Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Smith
authors.forename: Yecenia
authors.initials: Y
authors.lastname: Sierra
authors.forename: Scott H
authors.initials: SH
authors.lastname: Oppler
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Boettiger
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003657:Decision Making / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011594:Psychometrics; D012201:Reward; D012463:Saliva / Q000378:metabolism; D015983:Selection Bias; D055815:Young Adult
chemical_list: D004958:Estradiol; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: COMT; decision-making; delay discounting; dopamine; estrogen; impulsivity
references.citation: J Abnorm Psychol. 1956 Mar;52(2):240-5
references.pmid: 13306440
references.citation: J Neurosci. 2010 Jun 30;30(26):8888-96
references.pmid: 20592211
references.citation: Exp Clin Psychopharmacol. 2008 Apr;16(2):113-23
references.pmid: 18489015
references.citation: Psychopharmacology (Berl). 2008 Aug;199(2):161-8
references.pmid: 18551282
references.citation: Cereb Cortex. 2013 Jul;23(7):1695-702
references.pmid: 22693341
references.citation: Asia Pac Psychiatry. 2013 Mar;5(1):31-8
references.pmid: 23857789
references.citation: Psychopharmacology (Berl). 2014 Feb;231(3):521-31
references.pmid: 24062084
references.citation: Psychopharmacology (Berl). 2012 Aug;222(4):609-17
references.pmid: 22349272
references.citation: Behav Pharmacol. 2006 Dec;17(8):651-67
references.pmid: 17110792
references.citation: Front Integr Neurosci. 2011 Oct 14;5:63
references.pmid: 22016725
references.citation: Cereb Cortex. 2007 May;17(5):1206-12
references.pmid: 16835293
references.citation: Alcohol Clin Exp Res. 2010 Aug;34(8):1319-33
references.pmid: 20528825
references.citation: Science. 1986 May 23;232(4753):1004-7
references.pmid: 2422758
references.citation: Psychol Monogr. 1966;80(1):1-28
references.pmid: 5340840
references.citation: J Neurochem. 2010 Sep;114(6):1745-55
references.pmid: 20626558
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2003 Apr 1;118B(1):103-9
references.pmid: 12627475
references.citation: Arch Gen Psychiatry. 2002 Sep;59(9):851-8
references.pmid: 12215085
references.citation: Cancer. 2011 Apr 1;117(7):1369-76
references.pmid: 21425136
references.citation: Psychopharmacology (Berl). 2008 Sep;200(1):1-26
references.pmid: 18600315
references.citation: Addict Biol. 2009 Jan;14(1):22-31
references.pmid: 18855805
references.citation: Nat Rev Neurosci. 2009 Jun;10(6):410-22
references.pmid: 19455173
references.citation: Psychoneuroendocrinology. 2001 Aug;26(6):577-90
references.pmid: 11403979
references.citation: Stress. 2009 Sep;12(5):457-63
references.pmid: 19005873
references.citation: J Neurosci. 2011 Apr 6;31(14):5286-93
references.pmid: 21471363
references.citation: Science. 2010 Sep 10;329(5997):1358-61
references.pmid: 20829489
references.citation: Exp Clin Psychopharmacol. 2006 May;14(2):190-8
references.pmid: 16756423
references.citation: Alcohol Clin Exp Res. 2005 Dec;29(12):2158-69
references.pmid: 16385186
references.citation: Front Neuroendocrinol. 2006 Jul;27(2):210-6
references.pmid: 16650465
references.citation: Behav Processes. 2003 Oct 31;64(3):345-354
references.pmid: 14580703
references.citation: Front Neural Circuits. 2013 Oct 18;7:149
references.pmid: 24151456
references.citation: Neuro Endocrinol Lett. 2011;32(3):221-5
references.pmid: 21712792
references.citation: Biol Psychiatry. 2011 Jun 15;69(12):e113-25
references.pmid: 21531388
references.citation: Mol Psychiatry. 2008 Mar;13(3):325-33
references.pmid: 17579609
references.citation: Trends Cogn Sci. 2006 Sep;10(9):401-6
references.pmid: 16899395
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Mar;29(3):423-31
references.pmid: 15795051
references.citation: Neuro Endocrinol Lett. 2006 Aug;27(4):439-44
references.pmid: 16891992
references.citation: Child Adolesc Psychiatr Clin N Am. 2008 Apr;17(2):367-84, ix
references.pmid: 18295151
references.citation: Br J Pharmacol. 2011 Oct;164(4):1301-21
references.pmid: 21410459
references.citation: Neuropsychopharmacology. 2010 Nov;35(12):2414-26
references.pmid: 20736997
references.citation: Front Neurol. 2014 Jan 13;4:217
references.pmid: 24454304
references.citation: Neuropsychopharmacology. 2007 Feb;32(2):439-49
references.pmid: 17047667
references.citation: Pharmacol Biochem Behav. 2004 Sep;79(1):17-24
references.pmid: 15388279
references.citation: Science. 1991 Feb 22;251(4996):947-50
references.pmid: 1825731
references.citation: Behav Brain Funct. 2007 Jan 10;3:2
references.pmid: 17214892
references.citation: Behav Processes. 2011 May;87(1):10-7
references.pmid: 21354276
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11465-70
references.pmid: 17592140
references.citation: Soc Cogn Affect Neurosci. 2011 Oct;6(5):612-20
references.pmid: 20817665
references.citation: J Neurochem. 1995 Oct;65(4):1651-7
references.pmid: 7561861
references.citation: Alcohol Clin Exp Res. 2011 Nov;35(11):1905-14
references.pmid: 21569055
references.citation: Neuropsychopharmacology. 2009 Jul;34(8):1885-903
references.pmid: 19339966
references.citation: Psychopharmacology (Berl). 2012 Jan;219(2):469-90
references.pmid: 22057662
references.citation: Am J Hum Genet. 2004 Nov;75(5):807-21
references.pmid: 15457404
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9991-6
references.pmid: 9707588
references.citation: Psychoneuroendocrinology. 2011 Jan;36(1):123-32
references.pmid: 20675057
references.citation: Brain Cogn. 2010 Feb;72(1):146-59
references.pmid: 19944514
references.citation: Neuroreport. 2004 Sep 15;15(13):2145-7
references.pmid: 15486498
references.citation: J Comp Neurol. 1999 Jul 5;409(3):438-51
references.pmid: 10379829
references.citation: Mol Psychiatry. 2008 Aug;13(8):821-7
references.pmid: 18317466
references.citation: J Steroid Biochem Mol Biol. 2012 Aug;131(1-2):37-51
references.pmid: 22075082
references.citation: J Neurochem. 1994 Sep;63(3):972-9
references.pmid: 7914228
references.citation: Breast. 2012 Apr;21(2):199-203
references.pmid: 21974969
references.citation: J Cogn Neurosci. 2013 Dec;25(12):2061-71
references.pmid: 23937688
references.citation: Soc Cogn Affect Neurosci. 2014 Feb;9(2):191-200
references.pmid: 23175677
references.citation: Pharmacol Biochem Behav. 2008 Aug;90(2):250-60
references.pmid: 18272211
references.citation: Cereb Cortex. 2004 Feb;14(2):215-23
references.pmid: 14704219
references.citation: Nat Neurosci. 2008 Apr;11(4):410-6
references.pmid: 18368048
references.citation: Neuro Endocrinol Lett. 2010;31(5):616-21
references.pmid: 21178944
references.citation: J Clin Psychol. 1995 Nov;51(6):768-74
references.pmid: 8778124
references.citation: Exp Clin Psychopharmacol. 2009 Feb;17(1):51-61
references.pmid: 19186934
references.citation: J Clin Psychopharmacol. 2008 Feb;28(1):45-51
references.pmid: 18204340
references.citation: Neuroscience. 2010 May 19;167(3):709-15
references.pmid: 20219635
references.citation: Neuropsychopharmacology. 2002 Nov;27(5):813-25
references.pmid: 12431855
references.citation: Behav Genet. 2011 Mar;41(2):175-83
references.pmid: 20700643
references.citation: Brain. 2012 Aug;135(Pt 8):2449-57
references.pmid: 22843413
references.citation: Fertil Steril. 1999 May;71(5):863-8
references.pmid: 10231047
references.citation: J Neurosci. 2011 May 4;31(18):6771-9
references.pmid: 21543607
references.citation: Behav Brain Res. 2013 Mar 15;241:144-53
references.pmid: 23238042
references.citation: Psychoneuroendocrinology. 2002 Oct;27(7):835-41
references.pmid: 12183218
references.citation: Neuropsychopharmacology. 2007 Sep;32(9):1950-5
references.pmid: 17299513
references.citation: J Neurosci. 2007 Dec 26;27(52):14383-91
references.pmid: 18160646
references.citation: Neuroimage. 2012 Feb 1;59(3):2923-31
references.pmid: 21985908
references.citation: Neurosci Lett. 1994 Oct 24;180(2):155-8
references.pmid: 7700570
references.citation: Am J Psychiatry. 2001 Feb;158(2):308-11
references.pmid: 11156817
references.citation: J Abnorm Child Psychol. 2001 Dec;29(6):541-56
references.pmid: 11761287
references.citation: Brain Res Cogn Brain Res. 1996 Jun;3(3-4):227-42
references.pmid: 8806025
references.citation: Mol Psychiatry. 2004 May;9(5):531-8
references.pmid: 14569273
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2465-70
references.pmid: 17267613
references.citation: Nat Neurosci. 2007 Mar;10(3):376-84
references.pmid: 17277774
references.citation: J Neurosci. 2005 Oct 5;25(40):9309-16
references.pmid: 16207891
references.citation: Neuron. 2010 Apr 15;66(1):138-48
references.pmid: 20399735