Internal Medicine-Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA.
Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Geroscience. 2017 Dec;39(5-6):585-600. doi: 10.1007/s11357-017-9999-1. Epub 2017 Oct 28.
Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and activity, possibly depending on depressive status. The purpose of this preclinical trial was to determine the relationships of depressive behavior and the potential for an SSRI treatment to modulate walking speed and activity patterns in older adult female cynomolgus monkeys (Macaca fascicularis). We evaluated the effects of depression and a commonly prescribed SSRI, sertraline HCl (20 mg/kg/day p.o.), on (a) walking speed, (b) accelerometry-derived activity (counts) and sedentariness (daytime 60-s sedentary epochs), and (c) observed locomotor and sedentary behaviors (% time) in adult female depressed and nondepressed monkeys (n = 42; 17.2 ± 1.8 years) during an 18 month pre-treatment phase and an 18 month treatment phase using a longitudinal, stratified placebo-control study design. Monkeys that were depressed prior to treatment (19/42) subsequently had slower walking speeds (F [1, 38] = 4.14; p ≤ 0.05) and tended to be more sedentary during the daytime (F [1, 38] = 3.63; p ≤ 0.06). Sertraline did not affect depressive behaviors, walking speed, accelerometry-derived physical activity or sedentariness, or time observed in total locomotor or sedentary behavior (all p > 0.10). This study provides the first experimental demonstration of relationships between nonhuman primate behavioral depression and walking speed, activity, and sedentariness and provides evidence for a lack of an effect of SSRI treatment on these phenotypes.
抑郁症是老年人中最常见的心理健康问题，也是导致身体残疾的主要风险因素，尤其是在女性中。尽管经常开出处方抗抑郁药，如选择性 5-羟色胺再摄取抑制剂（SSRIs），但长期使用抗抑郁药对身体功能和活动的影响存在混合效应，这可能取决于抑郁状态。本临床前试验的目的是确定抑郁行为与 SSRI 治疗调节老年雌性食蟹猴（Macaca fascicularis）行走速度和活动模式的潜力之间的关系。我们评估了抑郁状态和一种常用的 SSRI 药物盐酸舍曲林（20mg/kg/天，口服）对（a）行走速度，（b）加速度计衍生的活动（计数）和久坐行为（白天 60 秒久坐期），以及（c）在 18 个月的预处理阶段和 18 个月的治疗阶段，通过纵向、分层安慰剂对照研究设计，观察到的运动和久坐行为（%时间）在成年雌性抑郁和非抑郁猴子（n=42；17.2±1.8 岁）中的作用。与治疗前抑郁的猴子（19/42）相比，治疗后的猴子行走速度较慢（F [1, 38] = 4.14；p≤0.05），白天更倾向于久坐（F [1, 38] = 3.63；p≤0.06）。舍曲林对抑郁行为、行走速度、加速度计衍生的身体活动或久坐行为或观察到的总运动或久坐行为时间没有影响（所有 p > 0.10）。这项研究首次提供了非人类灵长类动物行为性抑郁与行走速度、活动和久坐行为之间关系的实验证据，并提供了 SSRI 治疗对这些表型没有影响的证据。
