An integrated approach to understand biological stress system dysregulation across depressive and anxiety disorders

• Published in: Journal of affective disorders Vol. 283; pp. 139 - 146
• Main Authors: Vinkers, Christiaan H., Kuzminskaite, Erika, Lamers, Femke, Giltay, Erik J., Penninx, Brenda W.J.H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2021
• Subjects: Anxiety Disorders; Autonomic nervous system; Cross-Sectional Studies; Generalized anxiety disorder; Humans; Hydrocortisone; Hypothalamic-pituitary-adrenal axis (HPA-axis); Hypothalamo-Hypophyseal System; Immune system; Major depressive disorder; Netherlands; Panic disorder; Pituitary-Adrenal System; Psychiatric/Mental Health; Social anxiety disorder; Stress, Physiological; Netherlands; Generalized anxiety disorder; Autonomic nervous system; Panic disorder; Hypothalamic-pituitary-adrenal axis (HPA-axis); Social anxiety disorder; Major depressive disorder; Immune system
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2021.01.051

•Affective disorders involve dysregulation of major biological stress systems: the hypothalamic-pituitary-adrenal (HPA)-axis, the immune system, and the autonomic nervous system (ANS).•Depressive and anxiety disorders were significantly associated with changes in three biological stress systems including HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems.•To understand stress system functionality across affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important. Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary-adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems. In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-α), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period). Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (β=.124, pFDR=.001), the immune system (β =.057, pFDR=.032), and total cumulative index across stress systems (β=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases,or (especially for ANS-function) antidepressant use. Cross-sectional analyses limit examination of temporal associations. Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important.