The lipid paradox in neuroprogressive disorders: Causes and consequences. (September 2021)

• Record Type: Journal Article
• Authors: Morris, Gerwyn; Berk, Michael; Walder, Ken; O'Neil, Adrienne; Maes, Michael; Puri, Basant K.
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 128(2021)
• Page Start: 35
• Page End: 57
• Publication Date: 2021-09
• Subjects: Low-density lipoprotein -- Cholesterol -- Lipids -- Cardiovascular disease -- Major depressive disorder -- Bipolar disorder -- Schizophrenia -- Inflammation -- Atherosclerosis -- Neutrophils -- Hyperhomocysteinaemia -- Metabolic endotoxaemia; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2021.06.017
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Chronic systemic inflammation is associated with increased cardiovascular disease. It is also associated with the pathophysiology of neuroprogressive disorders. Both can occur with low LDL and low cholesterol: a lipid paradox. Inflammatory molecules released by activated neutrophils play a crucial role. The associated molecular mechanisms suggest potential therapeutic targets. Abstract: Chronic systemic inflammation is associated with an increased risk of cardiovascular disease in an environment of low low-density lipoprotein (LDL) and low total cholesterol and with the pathophysiology of neuroprogressive disorders. The causes and consequences of this lipid paradox are explored. Circulating activated neutrophils can release inflammatory molecules such as myeloperoxidase and the pro-inflammatory cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha. Since activated neutrophils are associated with atherosclerosis and cardiovascular disease and with major depressive disorder, bipolar disorder and schizophrenia, it seems reasonable to hypothesise that the inflammatory molecules released by them may act as mediators of the link between systemic inflammation and the development of atherosclerosis in neuroprogressive disorders. This hypothesis is tested by considering the association at a molecular level of systemic inflammation with increased LDL oxidation; increased small dense LDL levels; increased lipoprotein (a) concentration; secretory phospholipase A2 activation; cytosolic phospholipase A2 activation; increased platelet activation; decreased apolipoprotein A1 levels and function; decreased paroxonase-1 activity; hyperhomocysteinaemia; and metabolic endotoxaemia. These molecular mechanisms suggest potential therapeutic targets.