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Stress induced neural reorganization: A conceptual framework linking depression and Alzheimer's disease
Journal article   Open access   Peer reviewed

Stress induced neural reorganization: A conceptual framework linking depression and Alzheimer's disease

Jennifer A. Ross, Gediminas Gliebus and Elisabeth J. Van Bockstaele
Progress in neuro-psychopharmacology & biological psychiatry, v 85, pp 136-151
13 Jul 2018
DOI: https://doi.org/10.1016/j.pnpbp.2017.08.004
PMID: 28803923
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5809232View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Adrenergic receptors Amyloid Depression Dopamine-β-hydroxylase Norepinephrine Stress
Chronic stress is a risk factor for a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. There are a number of underlying molecular and cellular mechanisms altered in the course of chronic stress, which may increase the vulnerability of individuals to develop psychiatric disorders such as depression, and neurodegenerative disorders such as Alzheimer's Disease (AD). This is evident in the influence of stress on large-scale brain networks, including the resting state Default Mode Network (DMN), the effects of stress on neuronal circuitry and architecture, and the cellular and molecular adaptations to stress, which may render individuals with stress related psychiatric disorders more vulnerable to neurodegenerative disease later in life. These alterations include decreased negative feedback inhibition of the hypothalamic pituitary axis (HPA) axis, decreased dendritic arborization and spine density in the prefrontal cortex (PFC) and hippocampus, and the release of proinflammatory cytokines, which may suppress neurogenesis and promote neuronal cell death. Each of these factors are thought to play a role in stress-related psychiatric disease as well as AD, and have been observed in clinical and post-mortem studies of individuals with depression and AD. The goal of the current review is to summarize clinical and preclinical evidence supporting a role for chronic stress as a putative link between neuropsychiatric and neurodegenerative disease. Moreover, we provide a rationale for the importance of taking a medical history of stress-related psychiatric diseases into consideration during clinical trial design, as they may play an important role in the etiology of AD in stratified patient populations. •Stress induces widespread alterations to brain functioning, ranging from large-scale network activity to the altered expression and function of synaptic proteins.•Chronic stress results in a reorganization of neuronal circuitry such that limbic circuits are enhanced and cortical circuits are diminished.•Dysregulation of the Locus Coeruleus (LC)-Norepinephrine (NE) system, diminishes the ability to suppress the Default Mode Network (DMN).•Dysfunction of cortical regions involved in the DMN influences neural architecture of circuits involved in response to stressors.•Resultant reorganization manifests as a disconnection syndrome evidenced by psychiatric symptoms, including those observed in dementia.

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UN Sustainable Development Goals (SDGs)

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Web of Science research areas
Clinical Neurology
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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