Chronic HPA axis activation via CRH and glucocorticoids is proposed to partially mediate the neural effects of early life stress¶

Claim · All claims
Evidence · 1 study (2 entries) · review r2–r3 · q2
Currency · newest study 2020 · not yet checked against its sources · not reviewed by a person · overdue for a recheck since 2025: baselines and conditions change

Subclaims¶

q2 i? Animal experiments show blocking CRH receptors improved memory performance and prevented dendritic atrophy in the hippocampus, and restoring glucocorticoid receptor mRNA deficits or blocking glucocorticoid receptors reversed anxiety, social, and freezing behavior changes. → Karen E. Smith and Seth D. Pollak 2020 q2 i? In humans, epigenetic changes in glucocorticoids are associated with hippocampal changes, psychopathology symptoms, and altered learning, and abnormal HPA responsivity is often observed after varied early life stress experiences, varying with age. → Karen E. Smith and Seth D. Pollak 2020 (2)

Evidence¶

Karen E. Smith and Seth D. Pollak 2020¶

Karen E. Smith and Seth D. Pollak. (2020). Early life stress and development: potential mechanisms for adverse outcomes. Journal of Neurodevelopmental Disorders. https://doi.org/10.1186/s11689-020-09337-y

q2 · i? · review · r3

Narrative review synthesis of animal mediation experiments. The review reports that in rat pups exposed to fragmented maternal behaviors, "Blocking CRH receptors resulted in improved memory performance and prevented dendritic atrophy in the hippocampus," and describes glucocorticoid receptor mRNA restoration and receptor-blocking reversal experiments. No effect sizes are printed.

"Blocking CRH receptors resulted in improved memory performance and prevented dendritic atrophy in the hippocampus [ 93]. Chronic maternal separation stress in mice is associated with decreases in glucocorticoid receptor mRNA in the brain, especially so in the amygdala"

Karen E. Smith and Seth D. Pollak 2020 (2)¶

Karen E. Smith and Seth D. Pollak. (2020). Early life stress and development: potential mechanisms for adverse outcomes. Journal of Neurodevelopmental Disorders. https://doi.org/10.1186/s11689-020-09337-y

q2 · i? · review · r2

Narrative review synthesis of human studies of glucocorticoid-related mechanisms. The review states "there is some evidence that humans demonstrate similar epigenetic changes in glucocorticoids to those observed in non-human animals," associated with hippocampal changes, psychopathology, and altered learning. No effect sizes are printed.

"there is some evidence that humans demonstrate similar epigenetic changes in glucocorticoids to those observed in non-human animals, and these alter- ations are associated with changes in the hippocampus, symptoms of psychopathology, and altered learning pro- cesses [ 72, 116– 118]."

Discussion¶

Related Claims¶

• Chronicity, developmental timing, and intensity of adversity exposure shape children's neurobiological stress responses — related
• Early life stress disrupts dopaminergic reward circuitry in animals and humans, with altered reward learning and links to depressive and anxiety symptoms — a broader claim this one bears on
• Early life stress produces structural and functional alterations in prefrontal-hippocampal-amygdala circuits in animals and humans, with reduced hippocampal volume among the most reliable human findings — related
• Threat-related psychopathology associations appear more consistently mediated by stress response systems than deprivation-related ones — related
• Parental presence and support buffer children's neurobiological stress responses, mitigating adversity effects when support is high — related
• The probability of school failure increases as a function of the timing and length of children's exposure to relational adversity — related
• Exposure to adverse early circumstances affects the developing brain in ways that increase risk for later problems — a broader claim this one bears on