Editors' ChoiceNeuroscience

Stress Structures the Brain

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Science Translational Medicine  19 Dec 2012:
Vol. 4, Issue 165, pp. 165ec230
DOI: 10.1126/scitranslmed.3005489

Stress experienced early in life is associated with high rates of childhood- and adult-onset psychiatric disorders, as well as dysfunction of the key corticolimbic brain circuit that recognizes and adapts to stress. Early stress changes the function of the hypothalamic-pituitary-adrenal (HPA) axis, the hormonal coordinator of our stress responses. Specifically, the HPA axis produces cortisol, which directly affects the structure and function of the corticolimbic circuit. Now, Burghy et al. show that adolescents who experienced stress in early life have more anxiety and depression and decreased corticolimbic functional connectivity, a result of adversity-related elevations in blood cortisol in childhood.

The authors used a longitudinal approach to link early adversity with cortisol and brain functional connectivity dysfunction in response to stress. Fifty-seven adolescents from an ongoing Wisconsin Study of Families and Work were assessed for brain connectivity during rest with functional magnetic resonance imaging. These youths also reported their early life stress (estimated from maternal stress) and current symptoms of depression and anxiety and provided salivary samples for measurement of basal afternoon cortisol concentrations. In adolescent girls, but not boys, stress during infancy was positively associated with later childhood cortisol levels, which also predicted decreased resting-state functional connectivity between the amygdala and the ventromedial prefrontal cortex (vmPFC). Altered amygdala-vmPFC functional connectivity further predicted increased symptoms of adolescent anxiety and depression. Recently experienced stress was not associated with altered connectivity, suggesting that there is a sensitive period during development (before 1 year of age) during which exposure to stress appears to cause the later development of psychiatric symptoms, particularly in girls.

These results indicate that certain neural regions might be particularly vulnerable to early stress and suggest that females may be more sensitive to stress during this sensitive period than are males. This study had its limitations: a relatively small number of participants and only partial symptoms of anxiety and depression. In addition, the relations between brain functional connectivity, early life stress, and psychopathology were associative and not causal. Nonetheless, this research raises the intriguing possibility that interventions to reduce stress in early life could improve functioning in certain neurobiological pathways and prevent the onset of psychiatric disorders.

C. A. Burghy et al., Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat. Neuroscience 15, 1436–1741 (2012). [Full Text]

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