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Table 1 Selected effects of early life adversity (ELA) on physiological functioning

From: Biological embedding of childhood adversity: from physiological mechanisms to clinical implications

Examples of physiological changes observed after ELA Overall clinical and functional effects Key reviews
Brain structure and activity   
Structural variation in gray and white matter Increased risk of:
- Impairments in executive functioning (e.g., working memory, cognitive control)
- Impaired emotion regulation and social functioning
- Adverse effects on reward processing and stress regulation (e.g., hippocampus, amygdala, PFC) may increase risk of mood and substance use disorders
Bick & Nelson, 2016 [21]
Hart & Rubia, 2012 [24]
McEwen, 2013 [50]
Nemeroff et al., 2016 [25]
 1) Changes in local/global gray matter volumes
  a) Some evidence for widespread, global gray matter change
  b) Decreased gray matter volume of PFC and hippocampus
  c) Complex volumetric changes in amygdala
 2) Changes in local/global white matter volume and microstructure
  a) Complex white matter volumetric changes in frontal lobes
  b) Microstructural variation in various white matter tracts that may impair communication between brain regions
Functional variation in brain activity and functional connectivity
 3) Aberrant amygdala reactivity to emotional stimuli
 4) Alterations in amygdala-PFC connectivity
Altered neurotransmitter metabolism or production
 5) Potential altered neurotransmitter levels/signaling involving key molecules, e.g., serotonin, dopamine, GABA, glutamate
Neuroendocrine (HPA) stress response axes   
Hyper-responsiveness - Both HPA hyper- or hypo- reactivity are characteristic patterns generating excess “allostatic load,” linked to cardiovascular disease, metabolic syndrome, accelerated cellular aging, and various psychopathologies
- Downstream effects of aberrant cortisol levels (e.g., neurotoxicity, heightened inflammation, metabolic dysregulation) may drive pathology across other axes
Doom & Gunnar, 2015 [36]
Heim & Binder, 2012 [87]
 1) Enhanced ACTH and cortisol response to stress/stimulation
 2) Evidence of impaired GR-mediated feedback inhibition
Hypo-responsiveness
 4) Blunted HPA response (ACTH and cortisol) to stress/stimulation
 5) Heightened ACTH response with inappropriately blunted cortisol (normal or low)
Altered basal diurnal rhythms
 3) Elevated, or suppressed, average cortisol/CRF
 6) Complex changes to diurnal cortisol rhythms (e.g., lower morning and flatter decline, or higher morning and steeper decline)
Autonomic functioning   
 1) Complex patterns of sympathetic- or parasympathetic-predominant imbalance of reactivity to acute stress, with alterations in responsiveness and counter-regulatory control - Both parasympathetic- or sympathetic-predominant autonomic imbalances are linked to diseases of elevated “allostatic load” (discussed above) Alkon et al., 2012 [55]
El-Sheikh et al., 2009 [56]
 2) Elevated or decreased sympathetic or parasympathetic basal tone
Immunity and inflammation   
 1) Systemic immune suppression (e.g., impaired cellular immunity) - Chronic inflammation linked to increased cardiometabolic and other disease risk
- Immunosuppression linked to impaired control of infectious/neoplastic threats
Slopen et al., 2012 [66]
Baumeister et al., 2016 [67]
 2) Chronic basal inflammation (e.g., elevated CRP, TNF- α, IL-6)
 3) Heightened inflammatory reactivity
Metabolism   
 1) Impaired peripheral glucose handling with insulin resistance - Heightened risk of type 2 diabetes, obesity, hyperlipidemia, or other metabolic disease Maniam et al., 2014 [70]
 2) Altered fat metabolism with dyslipidemia
Microbiome functioning (emergent evidence, animal models only to date)
 1) Transient microbiome perturbations after stress in infancy linked to aberrant immune development - May contribute to inflammation, immune-suppression, and/or neurodevelopmental risk O’Mahony et al., 2015 [74]
 2) Possible durable microbiome changes in adults after early stress
  1. PFC prefrontal cortex, ACTH adrenocorticotropic hormone, GR glucocorticoid receptor, CRF corticotropin releasing factor, CRP C-reactive protein, TNF tumor necrosis factor, IL-6 interleukin-6, HPA hypothalamic-pituitary-adrenal