TY - JOUR

T1 - Oral contraceptives and the serotonin 4 receptor

T2 - a molecular brain imaging study in healthy women

AU - Larsen, S. V.

AU - Köhler-Forsberg, K.

AU - Dam, V. H.

AU - Poulsen, A. S.

AU - Svarer, C.

AU - Jensen, P. S.

AU - Knudsen, G. M.

AU - Fisher, P. M.

AU - Ozenne, B.

AU - Frokjær, V. G.

PY - 2020

Y1 - 2020

N2 - Objective: Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. Methods: [11C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. Results: We demonstrate that OC users have 9–12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (−12.8% (95% CI [−21.0; −3.9], Pcorrected = 0.03). Conclusion: We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.

AB - Objective: Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. Methods: [11C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. Results: We demonstrate that OC users have 9–12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (−12.8% (95% CI [−21.0; −3.9], Pcorrected = 0.03). Conclusion: We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.

KW - (11C)SB207145

KW - major depressive disorder

KW - oral contraceptives

KW - serotonin 4 receptor

KW - sex steroid hormones

U2 - 10.1111/acps.13211

DO - 10.1111/acps.13211

M3 - Journal article

C2 - 33314049

AN - SCOPUS:85088251905

VL - 142

SP - 294

EP - 306

JO - Acta Psychiatrica Scandinavica

JF - Acta Psychiatrica Scandinavica

SN - 0001-690X

IS - 4

ER -