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

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

 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