Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease.

Adverse Childhood Events (ACE), Post-Traumatic Stress Disorder (PTSD), and infectious encephalopathies are associated with immune-mediated diseases. Data supporting this are reviewed, and an integrated hypothesis is provided. All three can be associated with intrusive symptoms and temporal lobe pathology. ACE and PTSD are accompanied by an impaired mental capacity to differentiate external danger vs. safety. Infectious encephalopathies are accompanied by a failure of adaptive immunity and an impaired immune capacity to differentiate internal danger vs. safety. All three conditions are associated with impairments to differentiate danger vs. safety and adapt effectively. There are reciprocal interactions between ACE, PTSD, and infectious encephalopathies with accompanying persistent immune activation. This is associated with immune dysregulation, chronic hyperarousal, activation of the stress response, and impairments of the fear recognition and response neural circuits, hypothalamic-pituitary-adrenal axis, amygdala, and hippocampus. The pathophysiological processes can result in a broad spectrum of chronic neuropsychiatric and somatic symptoms and diseases. Understanding the psychodynamic, neurological, neuroimmune, inflammatory and autoimmune components of this interactive process expands the effective treatment opportunities.