From the Department of Psychology (Kuhlman, Bower), Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior (Kuhlman, Irwin, Bower), Jonsson Comprehensive Cancer Center (Ganz, Crespi, Petersen, Bower), Department of Biostatistics, Fielding School of Public Health (Crespi), and David Geffen School of Medicine (Irwin, Ganz), University of California Los Angeles; and Samuel Oschin Comprehensive Cancer Institute (Asher), Cedars-Sinai Medical Center, Los Angeles, California.
Psychosom Med. 2017 Sep;79(7):763-769. doi: 10.1097/PSY.0000000000000499.
The aim of the study was to investigate hypothalamic-pituitary-adrenal axis (HPA axis) functioning as a neurobiological risk factor for depressive symptoms in an ongoing longitudinal, observational study of women undergoing treatment and recovery from breast cancer. Many women with breast cancer experience depressive symptoms that interfere with their treatment, recovery, and quality of life. Psychosocial risk factors for depression among patients with cancer and survivors have been identified, yet neurobiological risk factors in this population remain largely unexamined.
Women recently diagnosed with early-stage breast cancer (N = 135) were enrolled before starting neoadjuvant/adjuvant treatment (radiation, chemotherapy, endocrine therapy). At baseline, participants collected saliva samples to measure diurnal HPA axis functioning for 3 days: at waking, 30 minutes after waking, 8 hours after waking, and bedtime. Participants also completed a standardized measure of depressive symptoms (Center for Epidemiological Studies-Depression Scale) at baseline and 6 months after completion of primary treatment. Multivariate regression was used to predict continuous depressive symptoms at 6-month posttreatment from continuous depressive symptoms at baseline, cortisol awakening response (CAR), and other measures of diurnal HPA axis functioning.
The magnitude of CAR predicted changes in depressive symptoms over time, such that women with a higher CAR showed a greater increase from baseline to 6-month posttreatment (b = 5.67, p = .023). Diurnal slope and total cortisol output were not associated with concurrent depressive symptoms or their change over time.
Elevated CAR may be a neurobiological risk factor for increases in depressive symptoms in the months after breast cancer treatment and warrants further investigation.
本研究旨在探讨下丘脑-垂体-肾上腺轴（HPA 轴）作为女性乳腺癌治疗和康复过程中持续性纵向观察研究中抑郁症状的神经生物学风险因素的作用。许多乳腺癌患者会出现抑郁症状，从而干扰其治疗、康复和生活质量。已确定癌症患者和幸存者中抑郁的心理社会风险因素，但该人群中的神经生物学风险因素仍在很大程度上未被研究。
在开始新辅助/辅助治疗（放疗、化疗、内分泌治疗）之前，招募了最近被诊断为早期乳腺癌的女性（N=135）。在基线时，参与者采集唾液样本以测量 3 天的日间 HPA 轴功能：醒来时、醒来后 30 分钟、醒来后 8 小时和睡前。参与者还在基线和主要治疗完成后 6 个月时完成了标准化的抑郁症状评估（流行病学研究中心抑郁量表）。使用多元回归来预测治疗后 6 个月时的连续抑郁症状从基线时的连续抑郁症状、皮质醇觉醒反应（CAR）和其他日间 HPA 轴功能测量值。
CAR 的幅度预测了随时间变化的抑郁症状的变化，即 CAR 较高的女性从基线到治疗后 6 个月的增加幅度更大（b=5.67，p=0.023）。日间斜率和总皮质醇输出与同期抑郁症状或其随时间的变化均无关联。
升高的 CAR 可能是乳腺癌治疗后数月内抑郁症状增加的神经生物学风险因素，值得进一步研究。
