Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

Frøkjær, Vibe G.; Pinborg, Anja; Holst, Klaus K.; Overgaard, Agnete; Henningsson, Susanne; Heede, M. Van den; Larsen, Elisabeth; Jensen, P.S.; Agn, Mikael; Nielsen, Arne E.; Stenbæk, Dea Siggaard; Cunha-Bang, Sofi da; Lehel, Szabolcs; Siebner, Hartwig R.; Mikkelsen, Jens D.; Svarer, Claus; Knudsen, Gitte M.

doi:10.1016/j.biopsych.2015.04.015

Cited by 119 publications

(132 citation statements)

References 64 publications

(55 reference statements)

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“…GnRHa-associated decrease in absolute estradiol and testosterone levels were inter-correlated (Pearson correlation = 0.40, p = 0.041, N = 26). The strict blinded design allowed for equal timing of baseline and follow-up with respect to phase (follicular), but not for cycle day, in the placebo group (Frokjaer et al, 2015). Accordingly, the placebo group was timed slightly later at follow-up and thus showed higher estradiol relative to baseline.…”

Section: Effects Of Gnrha On Hormone Levels and Depression Scoresmentioning

confidence: 99%

“…There were no significant differences in the levels of progesterone, testosterone, or Hamilton scores in the placebo group at follow-up (Table 1). The individual baseline and follow-up values for the Hamilton scores, estradiol, and progesterone can be found in Frokjaer et al (2015).…”

Section: Effects Of Gnrha On Hormone Levels and Depression Scoresmentioning

confidence: 99%

“…The participants were recruited by advertisement for participation in a large neuroimaging study, including both molecular and functional MRI investigations. Data on molecular imaging of the serotonin transporter are presented in Frokjaer et al (2015). The participants were screened by trained clinicians regarding their medical history.…”

Section: Study Design Participants and Interventionmentioning

confidence: 99%

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Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward

Macoveanu

Henningsson

Pinborg

et al. 2015

Neuropsychopharmacol

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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.

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Section: Effects Of Gnrha On Hormone Levels and Depression Scoresmentioning

confidence: 99%

Section: Effects Of Gnrha On Hormone Levels and Depression Scoresmentioning

confidence: 99%

Section: Study Design Participants and Interventionmentioning

confidence: 99%

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Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward

Macoveanu

Henningsson

Pinborg

et al. 2015

Neuropsychopharmacol

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“…Nevertheless, the contribution from 5-HTT across phases of sexsteroid hormone fluctuation and the timing of such serotonergic integration of ovarian steroid hormone information is far from clear and sparsely studied in humans. A recent study elegantly evaluated the interaction between mood and cerebral 5-HTT during hormonal fluctuation by using a gonadotropin-releasing hormone agonist (GnRHa) to induce a biphasic ovarian hormone response, with an initial increase in oestrogen levels and then subsequent decrease in healthy women (Frokjaer et al, 2015). Frokjaer et al (2015) found that the pharmacologically induced fluctuations in hormone levels triggered sub-clinical depressive responses in healthy women without any previous history of depressed mood.…”

Section: Periods Of Vulnerabilitymentioning

confidence: 99%

“…A recent study elegantly evaluated the interaction between mood and cerebral 5-HTT during hormonal fluctuation by using a gonadotropin-releasing hormone agonist (GnRHa) to induce a biphasic ovarian hormone response, with an initial increase in oestrogen levels and then subsequent decrease in healthy women (Frokjaer et al, 2015). Frokjaer et al (2015) found that the pharmacologically induced fluctuations in hormone levels triggered sub-clinical depressive responses in healthy women without any previous history of depressed mood. Symptom severity was positively correlated with magnitude of oestrogen decline and neocortical serotonin transporter increases.…”

Section: Periods Of Vulnerabilitymentioning

confidence: 99%

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

Zsido

Villringer

Sacher

2017

International Review of Psychiatry

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Ovarian hormones, particularly oestrogen and progesterone, undergo major fluctuations across the female lifespan. These hormone transition periods, such as the transition from pregnancy to postpartum, as well as the transition into menopause (perimenopause), are also known to be times of elevated susceptibility to depression. This study reviews how these transition periods likely influence neurochemical changes in the brain that result in disease vulnerability. While there are known associations between oestrogen/progesterone and different monoaminergic systems, the interactions and their potential implications for mood disorders are relatively unknown. Positron Emission Tomography (PET) allows for the in-vivo quantification of such neurochemical changes, and, thus, can provide valuable insight into how both subtle and dramatic shifts in hormones contribute to the elevated rates of depression during pre-menstrual, post-partum, and perimenopausal periods in a woman's life. As one better understands how to address the challenges of PET studies involving highly vulnerable populations, such as women who have recently given birth, one will gain the insight necessary to design and individualize treatment and therapy. Understanding the precise time-line in younger women when dramatic fluctuations in the hormonal milieu may contribute to brain changes may present a powerful opportunity to intervene before a vulnerable state develops into a diseased state in later life. ARTICLE HISTORY

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