BackgroundMajor depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepressant-treatment outcomes.MethodsWe determined pre-treatment AL and MetD in 67 healthy controls and 34 unmedicated, medically healthy MDD subjects. Following this, MDD subjects completed 8-weeks of open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and were categorized as ‘Responders’ (⩾50% improvement in depression severity ratings) or ‘Non-responders’ (<50% improvement). Logistic and linear regressions were performed to determine if pre-treatment AL or MetD scores predicted SSRI-response. Secondary analyses examined cross-sectional differences between MDD and control groups.ResultsPre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) (p = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder (p = 0.022 and 0.040, respectively), such that higher pre-treatment AL and MetD were associated with poorer SSRI-treatment outcomes. Pre-treatment AL and MetD of Responders were similar to Controls, while those of Non-responders were significantly higher than both Responders (p = 0.025 and 0.033, respectively) and Controls (p = 0.039 and 0.001, respectively).ConclusionsThese preliminary findings suggest that indices of metabolic and hypothalamic-pituitary-adrenal-axis dysregulation are associated with poorer SSRI-treatment response. To our knowledge, this is the first study to demonstrate that these markers of medical disease risk also predict poorer antidepressant outcomes.

中文翻译：

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治疗前非稳态负荷和代谢失调预测重度抑郁症中的 SSRI 反应：初步报告

背景重度抑郁症 (MDD) 与非稳态负荷增加（AL；重复/慢性应激反应的生理成本的测量）和代谢失调（MetD；代谢健康的测量和许多医学疾病的前兆）有关。尽管 AL 和 MetD 与较差的躯体健康结果相关，但关于它们与抗抑郁治疗结果的关系知之甚少。方法我们确定了 67 名健康对照者和 34 名未用药、医学上健康的 MDD 受试者的治疗前 AL 和 MetD。在此之后，MDD 受试者完成了为期 8 周的开放标签选择性 5-羟色胺再摄取抑制剂 (SSRI) 抗抑郁治疗，并被归类为“有反应者”（抑郁严重程度评分改善 50%）或“无反应者”（<50% 改善） ). 执行逻辑和线性回归以确定治疗前 AL 或 MetD 评分是否预测 SSRI 反应。二次分析检查了 MDD 和对照组之间的横截面差异。结果治疗前 AL 和 MetD 评分显着预测了持续的抗抑郁反应（即抑郁严重程度评分的绝对下降）（p= 0.012 和 0.014，分别），以及作为响应者或非响应者的治疗后状态（p= 0.022 和 0.040，分别），因此较高的治疗前 AL 和 MetD 与较差的 SSRI 治疗结果相关。反应者的治疗前 AL 和 MetD 与对照组相似，而无反应者的 AL 和 MetD 显着高于两个反应者（p= 0.025 和 0.033，分别）和控制（p= 0.039 和 0.001，分别）。结论这些初步研究结果表明，代谢和下丘脑-垂体-肾上腺轴失调指数与较差的 SSRI 治疗反应相关。据我们所知，这是第一项证明这些医学疾病风险标志物也能预测较差的抗抑郁效果的研究。