期刊
BIOLOGICAL PSYCHIATRY
卷 85, 期 6, 页码 443-453出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2018.09.031
关键词
Depression; Hippocampus; Illness progression; Medial prefrontal cortex; Neuroprogression; Stress
资金
- Harvard Medical School
- McLean Hospital
- Klingenstein Third Generation Foundation
- National Institute of Mental Health (NIH) [R00 MH102355, R01 MH108605]
- NIH [R37 MH068376, R01 MH101521, 1R01 MH108602, R01 MH095809]
Volumetric reductions in the hippocampus and medial prefrontal cortex (mPFC) are among the most well-documented neural abnormalities in major depressive disorder (MDD). Hippocampal and mPFC structural reductions have been specifically tied to MDD illness progression markers, including greater number of major depressive episodes (MDEs), longer illness duration, and nonremission/treatment resistance. Chronic stress plays a critical role in the development of hippocampal and mPFC deficits, with some studies suggesting that these deficits occur irrespective of MDE occurrence. However, preclinical and human research also points to other stress-mediated neurotoxic processes, including enhanced inflammation and neurotransmitter disturbances, which may require the presence of an MDE and contribute to further brain structural decline as the illness advances. Specifically, hypothalamic-pituitary-adrenal axis dysfunction, enhanced inflammation and oxidative stress, and neurotransmitter abnormalities (e.g., serotonin, glutamate, gamma-aminobutyric acid) likely interact to facilitate illness progression in MDD. Congruent with stress sensitization models of MDD, with each consecutive MDE it may take lower levels of stress to trigger these neurotoxic pathways, leading to more pronounced brain volumetric reductions. Given that stress and MDD have overlapping and distinct influences on neurobiological pathways implicated in hippocampal and mPFC structural decline, further work is needed to clarify which precise mechanisms ultimately contribute to MDD development and maintenance.
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