Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:87

Article

Swardfager, W.^1,2,3,4,5  Hennebelle, M.⁶  Yu, D.^1,2,3,4  Hammock, B. D.^7,8  Levitt, A. J.^1,2  Hashimoto, K.⁹  Taha, A. Y.⁶ 

[1] Sunnybrook Res Inst, Hurvitz Brain Sci Program, Toronto, ON, Canada

[2] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON, Canada

[3] Univ Toronto, Fac Med, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[4] Sunnybrook Res Inst, Canadian Partnership Stroke Recovery, Toronto, ON, Canada

[5] Univ Hlth Network, Toronto Rehabil Inst, Toronto, ON, Canada

[6] Univ Calif Davis, Coll Agr & Environm Sci, Dept Food Sci & Technol, Davis, CA 95616 USA

[7] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA

[8] Univ Calif Davis, Comprehens Canc Ctr UCDMC, Davis, CA 95616 USA

[9] Chiba Univ, Ctr Forens Mental Hlth, Div Clin Neurosci, Chiba, Japan

关键词: Omega-3 fatty acids;    Soluble epoxide hydrolase;    Lipidomics;    Depression;    Drug development;    ER stress;    NLRP3;    Inflammasome;    Metabolism;    Mitochondrial dysfunction;    Dementia;    Neuroprogression;    Neurodegeneration;    Obesity;    Diabetes;    Heart disease;    Stroke;   

DOI  :  10.1016/j.neubiorev.2018.01.010

来源: Elsevier

【 摘 要 】

The common and severe psychiatric disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are associated with inflammation, oxidative stress and changes in peripheral and brain lipid metabolism. Those pathways are implicated in the premature development of vascular and metabolic comorbidities, which account for considerable morbidity and mortality, including increased dementia risk. During endoplasmic reticulum stress, the soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory fatty acid epoxides generated by cytochrome p450 enzymes into their corresponding and generally less anti-inflammatory, or even pro-inflammatory, diols, slowing the resolution of inflammation. The sEH enzyme and its oxylipin products are elevated post-mortem in MDD, BD and schizophrenia. Preliminary clinical data suggest that oxylipins increase with symptoms in seasonal MDD and anorexia nervosa, requiring confirmation in larger studies and other cohorts. In rats, a soluble sEH inhibitor mitigated the development of depressive-like behaviors. We discuss sEH inhibitors under development for cardiovascular diseases, post-ischemic brain injury, neuropathic pain and diabetes, suggesting new possibilities to address the mood and cognitive symptoms of psychiatric disorders, and their most common comorbidities.

【 授权许可】

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