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