These developmental effects, combined with genetic variations, are believed to lead to changes in the way external stimuli are perceived and processed and can contribute to an overall increase in sensitivity to stress, according to Paul Plotsky, PhD, Emory GlaxoSmithKline professor of psychiatry and behavioral sciences, who conducted the research along with M. Mar Sanchez, PhD, and colleagues. This increased sensitivity to stress is a significant risk factor for the development of mood disorders and medical diseases.
In a series of studies in rodents and primates, the Emory researchers studied the development of pathways and circuitry in the brain to identify target areas that are vulnerable to negative events; sensitive time periods in brain development; and genes that potentially are associated with individual variation in vulnerability or resilience to changes in expectations of care-giving. Adverse events included perinatal social instability, neonatal maternal separation, and naturally occurring maltreatment.
Long-term effects related to adverse events included changes in the neuroendocrine system, increased anxiety, loss of the feeling of pleasure, changes in social behavior, changes in sexual behavior, and changes in cognitive performance. The researchers found that certain areas of the brain experience adaptations in structure, gene, and protein expression. Specific changes in expression of neurotransmitter genes and neurotransmitter hormones included corticotropin releasing factor (CRF), gamma aminobutyric acid (GABA), and norepinephrine, all of which are released in response to stress.
"This interrelated system of neurocircuits that are involved in perceiving and responding to stress has many targets that are programmed by external stimuli at different developmental stages," explains Dr. Plotsky. "If the brain is programmed at key developmental stages in early life to overreact to stressful stimuli, this stress reaction can carry over inappropriately into adult life."
The research was supported by the Silvio O. Conte Center for the Neuroscience of Mental Disease, the National Institutes of Health and the National Science Foundation.
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