Depressed, stressed, and inflamed: C‐reactive protein linked with depression symptoms in midlife women with both childhood and current life stress

Abstract

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self‐reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)‐6, IL 1‐beta (IL‐1β), tumour necrosis factor alpha (TNF‐α), and high sensitivity C‐reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0–1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0–1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest—clinically significant depression symptoms (CESD ≥16)—and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three‐way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three‐way interaction was not significant for IL‐6, IL‐1β, or TNF‐α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

The intersection between menopause and depression: overview of research using animal models

“…Exposure to psychosocial factors ( 8 , 19 ), either in early life or currently ( 191 ), is a strong predictor of depression in midlife. Once the stress axis is activated, the neurons of the paraventricular nucleus (PVN) are stimulated to release peptides, such as corticotropin-releasing hormone (CRH) and vasopressin (AVP), which act on the corticotropes of the anterior pituitary to stimulate the release of the adrenocorticotropic hormone (ACTH) into the portal system.…”

Menopause-Associated Depression: Impact of Oxidative Stress and Neuroinflammation on the Central Nervous System—A Review

“…The potential neuroendocrine mechanisms underlying how the complex hormonal changes during menopause may contribute to depressive symptoms remain unclear. Multiple hypothetical mechanisms are under investigation, including monoaminergic deficiency, reduction in neurotrophic factors, hypothalamic-pituitary-adrenal (HPA) axis dysfunction [45], oxidative stress [46,47], and low-grade chronic inflammation [48,49] during perimenopause.…”