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

被引：104

作者：

Frokjaer, Vibe Gedsoe ^{[1
,2
]}

Pinborg, Anja ^{[3
,6
]}

Holst, Klaus Kahler ^{[5
]}

Overgaard, Agnete ^{[2
]}

Henningsson, Susanne ^{[6
]}

Heede, Maria ^{[1
,2
]}

Larsen, Elisabeth Clare ^{[3
]}

Jensen, Peter Steen ^{[1
,2
]}

Agn, Mikael ^{[1
,2
]}

Nielsen, Anna Pors ^{[1
,2
]}

Stenbaek, Dea Siggaard ^{[1
,2
]}

da Cunha-Bang, Sophie ^{[1
,2
]}

Lehel, Szabolcs ^{[4
]}

Siebner, Hartwig Roman ^{[6
,7
,8
]}

Mikkelsen, Jens Damsgaard ^{[1
,6
]}

Svarer, Claus ^{[1
,2
]}

Knudsen, Gitte Moos ^{[1
,2
,6
]}

机构：

[1] Rigshosp, Ctr Integrated Mol Brain Imaging, DK-2100 Copenhagen, Denmark

[2] Rigshosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark

[3] Rigshosp, Fertil Clin, DK-2100 Copenhagen, Denmark

[4] Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark

[5] Univ Copenhagen, Dept Biostat, Copenhagen, Denmark

[6] Univ Copenhagen, Copenhagen, Denmark

[7] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, Ctr Funct & Diagnost Imaging & Res, DK-2650 Hvidovre, Denmark

[8] Bispebjerg, Dept Neurol, Copenhagen, Denmark

来源：

BIOLOGICAL PSYCHIATRY | 2015年 / 78卷 / 08期

关键词：

C-11]DASB-PET; Estradiol; Gonadotropin-releasing-hormone agonist; 5-HT; 5-HTT; Mood disorder; GONADOTROPIN-RELEASING-HORMONE; NATIONAL COMORBIDITY SURVEY; MONOAMINE OXIDASE-A; MATERNAL DEPRESSION; POSTPARTUM DEPRESSION; REUPTAKE TRANSPORTER; MENTAL-DISORDERS; OVARIAN-STEROIDS; RECEPTOR-BINDING; 5-HT1A RECEPTOR;

D O I：

10.1016/j.biopsych.2015.04.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. METHODS: A double-blind, randomized, placebo-controlled study included 63 healthy female volunteers (mean age 24.3 +/- 4.9 years) with regular menstrual cycles between 23 and 35 days. Participants were randomized to active (goserelin [GnRHa] 3.6 mg implant) or placebo intervention. Sixty women completed follow-up and entered the analyses. Primary outcome measures were changes from baseline in depressive symptoms assessed on the 17-item Hamilton Depression Rating Scale and SERT binding as imaged by [C-11]DASB positron emission tomography. Outcome measures were acquired at baseline in the follicular phase (cycle day 6.6 +/- 2.2) and at follow-up (16.2 +/- 2.6 days after intervention start). RESULTS: Sex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group (p = .003) and relative to placebo (p = .02), which were positively associated with net decreases in estradiol levels (p = .02) from baseline within the GnRHa group. Depressive symptoms were associated with increases in neocortical SERT binding in the GnRHa group relative to placebo (p = .003). CONCLUSIONS: Our data imply both serotonergic signaling and estradiol in the mechanisms by which sex-steroid hormone fluctuations provoke depressive symptoms and thus provide a rationale for future preventive strategies in high-risk groups.

引用

页码：534 / 543

页数：10

共 62 条

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