Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression.

IF 4.9 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-01-29 DOI:10.1186/s13293-024-00587-2

Xiaofeng Lan, Haiyan Liu, Chengyu Wang, Weicheng Li, Fan Zhang, Zhibo Hu, Xiaoyu Chen, Zerui You, Yuping Ning, Yanling Zhou

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Abstract

Background: Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.

Methods: A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).

Results: Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).

Conclusions: Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn.

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重复注射氯胺酮对单相抑郁症和双相抑郁症患者骨标记物影响的性别差异。

背景：抑郁症患者（尤其是女性）的骨质密度（BMD）较低。传统的抗抑郁药对骨密度有负面影响。目前还不清楚氯胺酮对抑郁症患者骨密度的影响是否存在性别差异：共有 102 名单相和双相抑郁症患者在 12 天内接受了六次氯胺酮静脉注射。在基线、第六次输液后 24 小时以及两周后（第 13 天和第 26 天）对八种骨标志物的血浆水平进行了检测：线性混合模型显示，所有骨标记物都有显著的时间主效应（均为 p我们的研究结果表明，重复输注氯胺酮可能与抑郁症患者骨标记物的调节有关，并存在性别差异。基线骨钙素水平可作为氯胺酮对男性抗抑郁作用的预测因子。试验注册数据来自一项开放标签临床试验，该试验已在中国临床试验注册中心注册（ChiCTR-OOC-17012239）。注册时间为2017年5月26日。http://www.chictr.org.cn。

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来源期刊

Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY

CiteScore

12.10

自引率

1.30%

发文量

审稿时长

14 weeks

期刊介绍： Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.