title: Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.
abstract: Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.|Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Psychiatric Center Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Julian
authors.initials: J
authors.lastname: Macoveanu
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.|Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Henningsson
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Fertility Clinic, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Gynecology and Obstetrics, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Pinborg
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Jensen
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Psychiatric Center Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.|Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D003863:Depression / Q000097:blood / Q000503:physiopathology*; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood / Q000502:physiology; D005260:Female; D005715:Gambling; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D011374:Progesterone / Q000097:blood / Q000502:physiology; D012201:Reward; D012306:Risk; D013739:Testosterone / Q000097:blood / Q000502:physiology; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol