Neuroimmunoendocrine Interactions in Post-Traumatic Stress Disorder: Focus on Long-Term Implications of Childhood Maltreatment

Abstract

Childhood maltreatment has been linked to enhanced vulnerability to psychiatric pathologies in adult life, including post-traumatic stress disorder (PTSD). Previous works have reported cogent neuroendocrine and immune changes related to adult traumatic events (war survivors, refugees, etc.), but little information is known regarding the impact of early-life stress (ELS) in adult physiology. Here, we review the neuroendocrine and immunological changes commonly observed in PTSD, focusing on the long-term implications of ELS. Childhood maltreatment may lead to altered glucocorticoid (GC) secretion, resulting in hypo- or hypercortisolemia, and reciprocal changes in peripheral leukocyte sensitivity to GC. It is believed that these neuroendocrine changes are correlated with the immune imbalance phenomenon (low-grade inflammation), characterized by increased plasma levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and C-reactive protein. Changes in peripheral lymphocyte subsets are also documented, such as a reduction in regulatory T cells and an expansion of activated T cells. The excess of circulating cytokines may thus interfere with key brain neurotransmitter pathways involved in depression and enhanced risk to cardiovascular, respiratory, gastrointestinal, inflammatory and autoimmune diseases. Recent gene-environment and epigenetic findings have indicated potential molecular mechanisms linking ELS, neuroendocrine and immunity in PTSD.

Intergenerational Transmission of Maternal Childhood Maltreatment Exposure: Implications for Fetal Brain Development

“…6,36 The capacity to respond to maltreatment with temporally stable physiologic and behavioral changes may be due to epigenetic alterations. 35,37 These CM-associated alterations in endocrine and immune function have implications for responsivity to subsequent stress exposures, and they are believed to constitute a crucial link between CM exposure and adult disorders such as PTSD, 38,39 major depression, 2,40,41 and obesity. 4,42 Moreover, some studies suggest that the co-occurrence of CM-associated affective disorders is associated with exacerbation of the adverse neurobiological consequences of CM exposure.…”

(Putative) sex differences in neuroimmune modulation of memory

“…Women, for example, have higher rates of Alzheimer’s disease (Seshadri et al, 1997) and stress-related disorders including post-traumatic stress disorder (Kessler et al, 2012). Inflammatory signaling increases the risk of neurodegenerative disease (e.g., Tan et al, 2007; Azizi et al, 2014) or stress-related disorders (Wieck et al, 2014; Vecchiarelli et al, 2015; McKim et al, 2016). Thus understanding the similarities and differences in neuroimmune activation in males and females may help identify the specific components of immune signaling that confer higher risk and provide new, sex-specific avenues for prevention and treatment of memory disorders.…”

“…In patients of major surgery or illness, persistent cognitive deficits are common and correlate with levels of inflammatory signaling (Hovens:2014ib Petrovitch et al, 1998; Hudetz et al, 2009; Girard et al, 2010). Dysregulated immune activity contributes to neurological and psychiatric disorders of memory, including Alzheimer’s disease and post-traumatic stress disorder (Azizi et al, 2014; Wieck et al, 2014; Dzamba et al, 2016). Immune-related signaling is an important mechanism for synaptic plasticity and memory, as well as persistent cognitive dysregulation, after major illness and in psychiatric and neurological diseases.…”

Elevated hair cortisol concentrations in recently fled asylum seekers in comparison to permanently settled immigrants and non-immigrants

“…It has been proposed that such a change was a result of the counter-regulatory processes of the HPA axis and might also represent specific pathophysiological processes of neuroendocrine and immune changes following trauma and chronic stress. 21, 22, 23 However, more studies are needed to shed light on this issue. Moreover, so far, no study has investigated HCC in asylum seekers with and without PTSD.…”