Review article
Developmental neurobiology of childhood stress and trauma

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Overview of postnatal brain development

The human brain contains billions of neurons and trillions of synaptic interconnections. Genes dictate the basic architecture, but there is insufficient genetic information to detail the specific wiring. The final form and connection patterns are sculpted by experience.

The brain develops through a series of overlapping stages. Before birth, the developing brain contains two to three times the full adult complement of immature neurons, which migrate to their final positions and arborize in an

Basic outline of the cascade model

The cascade model is built on five fundamental premises. First, exposure to stress early in life activates stress-response systems and fundamentally alters their molecular organization to modify their sensitivity and response bias. Second, exposure of the developing brain to stress hormones affects myelination, neural morphology, neurogenesis, and synaptogenesis. Third, different brain regions differ in their sensitivity, which depends, in part, upon genetics, gender, timing, rate of

Molecular consequences of early stress

The first step in the cascade is the enduring effects of stress on the molecular components of the stress-response system. There are three major pillars to this system. One pillar involves the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and is intimately involved in the feedback regulation of cortisol. This is an indispensable stress hormone, which mobilizes energy stores; potentiates the release of adrenaline; increases cardiovascular tone; and inhibits growth, immune, and

Stress hormone effects on the developing brain

The second stage of the cascade model centers on the effects of increased activation of the stress hormone systems on the developing brain. In particular, corticosteroids have dramatic and profound effects on the developmental process. Research in laboratory animals has shown that GC administration during early life permanently reduces brain weight and DNA content [40], suppresses postnatal neural mitosis of granule cells in the cerebellum and dentate gyrus [41], and interferes with

Reframing the effects of early stress from an evolutionary perspective

Initially, our view was that early stress evokes a cascade of neurohumeral and neurotransmitter effects that produce enduring deleterious alterations in brain function. In this narrow perspective, we viewed excessive stress simply as a toxic agent that interfered with the normal smooth orchestrated progression of brain development, producing a somewhat altered and impaired brain [1], [69], [70], [75], [78], [112]. We also postulated that the neuropsychiatric consequences associated with early

Acknowledgements

This work was supported by NIMH grants RO1 MH43743 and MH53636 (MHT). Carl Anderson was supported by a special supplement to MH53636.

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