Stress and anxiety: Structural plasticity and epigenetic regulation as a consequence of stress

Abstract

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult, as well as developing brain, possess a remarkable ability to show reversible structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. This is particularly evident in the hippocampus, where all three types of structural plasticity have been recognized and investigated, using a combination of morphological, molecular, pharmacological, electrophysiological and behavioral approaches. The amygdala and the prefrontal cortex, brain regions involved in anxiety and fear, mood, cognitive function and behavioral control, also show structural plasticity. Acute and chronic stress cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. In the short term, such as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive; but, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic or mood anxiety disorders. We shall review cellular and molecular mechanisms, as well as recent work on individual differences in anxiety-like behavior and also developmental influences that bias how the brain responds to stressors. Finally, we suggest that such an approach needs to be extended to other brain areas that are also involved in anxiety and mood.

Stress and the dynamic genome: Steroids, epigenetics, and the transposome

“…In the orbitofrontal cortex and basolateral amygdala, the pattern of stress-induced structural plasticity is reversed, with exposure to chronic stress increasing dendritic complexity and synaptic number in parallel with increased vigilance, aggressiveness, and anxiety (27,28). These findings from animal models fit well with a substantial body of findings linking exposure to stress and elevated levels of adrenal steroids to reduced hippocampal volume (3,29). These effects also seem to be at least partially reversible with exercise and environmental enrichment (19,30,31), which also seems to elevate levels of neurogenesis in man, as it does in model animals (32).…”

Childhood Maltreatment and Coping in Bipolar Disorder

“…maternal isolation/separation or isolation rearing) show that the mPFC is particularly affected by early life emotional stress [55][56][57][58][59][60]. In line, patients and healthy controls reporting CEM show a reduction in dorsal mPFC volume [61][62][63], and dorsal mPFC hypo-activity during higher order cognitive processing [unpublished data].…”

Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration

“…The hippocampus, which is densely populated with glucocorticoid receptors, is hypothesized to inhibit emotional responses to stressful stimuli via negative feedback of the hypothalamic-pituitary-adrenal axis (55). Chronic negative emotional reactivity and its accompanying autonomic-neuroendocrine cascade potentiate amygdala-dependent behavior [e.g., anxiety-like behavior (56), aggression (57), and fear conditioning (58)] by inducing reorganization of medial temporal circuitry (i.e., increased dendritic branching in the amygdala and simplification of dendritic branching in the hippocampus) (56,59,60). Although most studies suggest that heightened emotional reactivity causes hippocampal simplification and amygdalar elaboration at the neuronal level (59), there is evidence from human (61) and animal (62,63) studies that smaller hippocampal volume at baseline and laboratory-induced hippocampal lesions can precede the behavioral manifestations of hyperemotionality.…”