Disconnection and reconnection: the morphological basis of (mal)adaptation to stress

Maladaptive responses to stress and the associated hypersecretion of glucocorticoids cause psychopathologies ranging from hyperemotional states and mood dysfunction to cognitive impairments. Research in both humans and animal models has begun to identify morphological correlates of these functional changes. These include dendritic and synaptic reorganization, glial remodeling, and altered cell fate in cortical and subcortical structures. The emerging view is that stress induces a ‘disconnection syndrome’ whereby the transmission and integration of information that are critical for orchestrating appropriate physiological and behavioral responses are perturbed. High-resolution spatiotemporal mapping of the complete neural circuitry and identification of the cellular processes impacted by stress will help to advance discovery of strategies to reduce or reverse the burden of stress-related neuropsychiatric disorders.