一氧化氮和重度抑郁障碍：病理生理学及治疗意义

Title:Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications

Volume: 16 Issue: 2

Author(s): P. Kudlow, D.S. Cha, A.F. Carvalho and R.S. McIntyre

Affiliation:

关键词: 抑郁症，一氧化氮，炎症，氧化应激，一氧化氮合酶，内表型，综述。

摘要: Major depressive disorder (MDD) is a multi-factorial and heterogeneous disease. Robust evidence suggests that inflammation is involved in the pathogenesis of MDD for a subpopulation of individuals. However, it remains unclear what traits and/or states precede the onset of inflammation in this subpopulation of individuals with MDD. Several recent studies have implicated nitric oxide (NO) as a critical regulator of neuroinflammation, thus suggesting a possible role in the pathophysiology of MDD. The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for developing MDD in certain subpopulations may be mediated, in part, by inflammogenic trait and/or state variations in NO signaling pathways. We conducted a non-systematic literature search for English language studies via PubMed and Google Scholar, from 1985 to October 2014. Replicated evidence suggests that NO has contrasting effects in the central nervous system (CNS). Low concentrations of NO are neuroprotective and mediate physiological signaling whereas higher concentrations mediate neuroinflammatory actions and are neurotoxic. Certain polymorphisms in the neuronal nitric oxide synthase gene (NOS1) are associated MDD. Furthermore, state variations (e.g. decreased levels of essential co-factor, 5,6,7,8-tetrahydrobiopterin [BH4], enhanced microglial cell activity) in the NO signaling pathway are associated with an increased risk of developing MDD. Increased concentrations of NO enhance the production of reactive nitrogen species (RNS) and reactive oxygen species (ROS), which are associated with an increase in pro-inflammatory cytokines. Taken together, evidences suggest that abnormalities in NO signaling may constitute a trait-marker related to MDD pathophysiology, which could be explored for novel therapeutic targets.

Cite this article as:

P. Kudlow, D.S. Cha, A.F. Carvalho and R.S. McIntyre , Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications, Current Molecular Medicine 2016; 16 (2) . https://dx.doi.org/10.2174/1566524016666160126144722