Neurobiological and Systemic Effects of Chronic Stress

Abstract

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor, which promote adaptation (“allostasis”) but also contribute to pathophysiology (“allostatic load/overload”) when overused and dysregulated. The adult as well as developing brain possesses a remarkable ability to show structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling and synapse turnover. Stress can cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, these changes may be adaptive; but, if the threat passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation requires intervention with a combination of pharmacological and behavioral therapies. There are important sex differences in how the brain responds to stressors. Moreover, adverse early life experience, interacting with alleles of certain genes, produces lasting effects on brain and body via epigenetic mechanisms. While prevention is key, the plasticity of the brain gives hope for therapies that utilize brain–body interactions. Policies of government and the private sector are important to promote health and increase “healthspan.”

Transdiagnostic trauma severity in anxiety and mood disorders: Functional brain activity during emotional scene processing

“…Moreover, the current data suggest that a deficit in visual sensory processing—a failure to discriminate motivational cues—is not limited to PTSD but, instead, is present across the spectrum of internalizing disorders and is not limited to aversive stimuli but is also found for appetitive cues. Given the strong covariation between functional activation in the amygdala and ventral visual cortex observed here, together with data supporting re‐entrant amygdala‐visual processing (Sabatinelli et al, ), the deficits in visual cortical processing found for those exposed to trauma could reflect effects of chronic stress on amygdala circuitry or function (McEwen, ; Vyas, Miltra, Shankaranarayana Rao, & Chattarji, ) or, alternatively or in addition to, HPA axis dysfunction (Ross, Foster, & Ionescu, ).…”

“…Traumatic events are, of course, not unique to PTSD, and previous research suggests that trauma exposure is frequently involved in other internalizing disorders, for example, in depression (Starr & Moulds, ), social anxiety (Wild, Hackmann, & Clark, ), and panic disorder (Bandelow et al, ). As highlighted in diathesis stress models (e.g., Belsky & Pluess, ; McEwen, ), exposure to stressful events is a significant factor in the development of physical and mental disease across the diagnostic spectrum. Thus, our research follows the NIMH Research Domain Criteria (RDoC) initiative: “To explore potential dimensional, biological measures of psychopathology, unconstrained by current diagnostic categories” (e.g., Insel & Cuthbert, ).…”

Capability and adversity: reframing the “causes of the causes” for mental health

“…The phrase "toxic stress" was coined to describe "what happens when children experience severe, prolonged adversity without adult support"(National Scientific Council on the Developing Child, 2014), and the impact of long-term stress on a range of body systems (including immune and endocrine responses, epigenetics, and brain development) is well-characterised (Shonkoff and Garner, 2012;McEwen, 2017). Research has confirmed that the risks associated with ACEs can be mitigated by the presence of a trusted adult being available throughout childhood (Bellis et al, 2017).…”

Stress and the psyche–brain–immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review

“…Stress is the physiological response of the body to any demand: biological, emotional, and cognitive . Whereas acute stress may induce dynamic adaptation to different demands, chronic stress can have long‐lasting maladaptive effects, with pathologic consequences on nervous, immune, endocrine, and metabolic systems . Many psychosocial conditions entailing high levels of chronic stress, that is, poor socioeconomic state, adverse life events, loneliness, experiences of trauma and/or abuse, have been associated with network dysregulation and are thought to be relevant clinical risk factors.…”