Neuroendocrine and Inflammatory Effects of Childhood Trauma Following Psychosocial and Inflammatory Stress in Women with Remitted Major Depressive Disorder

Abstract

The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of childhood trauma. In a single-blind randomized placebo-controlled crossover study, 21 women with remitted recurrent MDD and 18 healthy controls were exposed to psychosocial stress (Trier social stress test) or inflammatory stress (typhoid vaccine), or both, to investigate the effects of childhood trauma on the neuroendocrine and inflammatory responses. Childhood trauma was assessed using the Childhood Trauma Questionnaire and participants were dichotomized into a traumatized and non-traumatized group. Serum adrenocorticotropic hormone (ACTH), cortisol, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured at regular intervals after each intervention. The effects of trauma, time, and intervention on these parameters were modeled by fitting linear mixed models. Childhood trauma in itself did not have a main effect on the outcome measurements. However, an interactional effect of trauma with stressor type was found in the remitted MDD group: trauma was associated with higher cortisol levels only after adding immunological to psychosocial stress, and with lower TNF-α levels in response to vaccination. This suggests the existence of a vulnerable trauma-associated MDD endophenotype.

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders

“…brain-derived neurotrophic factor) and trigger the release of HPA axis-related hormones, which can in turn impact depression (Cassiers et al, 2019). Experiences of chronic and uncontrollable stress (as emphasised in learned helplessness models of depression) exacerbate negative attributional style (Alloy et al, 1984) and trigger a self-reinforcing cascade of neuroendocrine and inflammatory processes that result in further sensitisation to depressive states among susceptible individuals (Cassiers et al, 2019; Richter-Levin and Xu, 2018). Differential methylation in human spermatozoa has been found in victims of childhood maltreatment, providing a possible mechanistic link between such environmental adversity and epigenetic modification of gene expression (Roberts et al, 2018).…”

Immune response to vaccination in adults with mental disorders: A systematic review

“… Unknown; years after childhood vaccination Antibodies cMDD and rMDD were less likely to test seropositive for measles (p=0.015, adj OR=0.53, 95% CI: 0.74-2.37). BD: did not differ from HC (p=0.329) or cMDD (0.355) or rMDD (0.449) ( Cassiers et al, 2019 ) Remitted MDD (rMDD), including Moderate-to-severe recurrent MDD without psychotic features Criteria: DSM-IV-TR Most recent depressive episode was within 24 months, but stable for the past 3 months rMDD (n = 21) Controls (n = 18) Typhoid vaccine (0.5 mL containing 23 ug Salmonella typhi capsular polysaccharide; Typhim Vi; Sanofi Pasteur MSD, Diegem, Belgium) Placebo: 0.5 mL NaCl, 0.9% Baseline and 30, 60, 90, 150, 180, 240, 360 min post-vaccine Proinflammatory cytokines: interferon (IFN)-y, tumor necrosis factor (TNF)-a, and interleukin (IL)-6 Trauma was associated w lower TNF-a after vaccination for rMDD but not HC (suggests a "trauma-associated MDD endophenotype"). Found no effects of trauma on IL-6 and IFN-y in rMDD or HC after statistical correction.…”

“…The risk of bias assessments are displayed in Table 2 . All five studies on schizophrenia had a moderate risk of bias due to a lack of controlling for confounding factors ( Hussar et al, 1971 ; Solomon et al, 1968 ; Friedman et al, 1967 ; Vaughan et al, 1949 ; Wang et al, 2015 ), and all three studies on MDD/rMDD had a low risk of bias ( Ford et al, 2019 ; Niemegeers et al, 2017 ; Casseirs et al, 2019 ). Both the study on insomnia ( Taylor et al, 2017 ) and OSA ( Dopp et al, 2007 ) had low risks of bias, as did the study on PTSD ( Kosor Krnic et al, 2007 ) and the anorexia study by Armstrong-Esther et al (1978) .…”

“…Three studies reported on adults with MDD or remitted MDD and immune response to vaccination ( Ford et al, 2019 ; Niemegeers et al, 2017 ; Casseirs et al, 2019 ). Ford et al (2019) measured serum levels of IgG antibodies against measles in subjects with current mild, moderate, or severe MDD (cMDD; n = 85), and subjects with MDD in full or partial remission (rMDD; n = 82).…”

Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders

“…Immune mechanisms are further known to modulate psychiatric symptom development and illness course. Specifically, inflammation-induced depressive symptomatology has been observed in healthy volunteers and patients recently remitted from major depression ( 8 , 9 ), while add-on anti-inflammatory drugs improve residual symptoms in patients with major depressive disorder (MDD) and psychotic disorders. This effect is particularly observed if patients present with a basally increased peripheral pro-inflammatory cytokine profile ( 10 , 11 ).…”