Early Life Stress and Major Depressive Disorder-An Update on Molecular Mechanisms and Synaptic Impairments.

Mol Neurobiol

Laboratory of Physiology Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, 89815-899, Brazil.

Published: September 2024

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms.

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http://dx.doi.org/10.1007/s12035-024-03983-2DOI Listing

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