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

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• 作者：Vibe Gedsoe Frokjaer^a ; ^b ; ^{vibe@nru.dk" class="auth_mail" title="E-mail the corresponding author} ; Anja Pinborg^c ; ^f ; Klaus Kä ; hler Holst^e ; Agnete Overgaard^b ; Susanne Henningsson^f ; Maria Heede^a ; ^b ; Elisabeth Clare Larsen^c ; Peter Steen Jensen^a ; ^b ; Mikael Agn^a ; ^b ; Anna Pors Nielsen^a ; ^b ; Dea Siggaard Stenbæ ; k^a ; ^b ; Sophie da Cunha-Bang^a ; ^b ; Szabolcs Lehel^d ; Hartwig Roman Siebner^g ; ^f ; ^h ; Jens Damsgaard Mikkelsen^a ; ^f ; Claus Svarer^a ; ^b ; Gitte Moos Knudsen^a ; ^b ; ^f
• 关键词：[11C]DASB-PET ; Estradiol ; Gonadotropin-releasing-hormone agonist ; 5-HT ; 5-HTT ; Mood disorder
• 刊名：Biological Psychiatry
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：78
• 期：8
• 页码：534-543
• 全文大小：432 K

文摘

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 [¹¹C]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.