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.

常见的和严重的精神疾病，包括重度抑郁症（MDD）和双相情感障碍（BD），与炎症，氧化应激以及外周和脑脂质代谢的变化有关。这些途径涉及血管和代谢合并症的过早发展，这导致相当高的发病率和死亡率，包括痴呆症的风险增加。在内质网应激期间，可溶性环氧化物水解酶（sEH）酶将由细胞色素p450酶产生的抗炎性脂肪酸环氧化物转化为它们相应的，通常抗炎性甚至更低的促炎性二醇，从而减缓了炎症的消退。sEH酶及其脂蛋白产物在MDD，BD和精神分裂症的验尸后升高。初步临床数据表明，在季节性MDD和神经性厌食症中，随着时间的推移，磷脂素会随着症状的增加而增加，这需要在更大的研究和其他队列研究中得到证实。在大鼠中，可溶性sEH抑制剂减轻了抑郁样行为的发展。我们讨论了正在开发的用于心血管疾病，缺血后脑损伤，神经性疼痛和糖尿病的sEH抑制剂，为解决精神疾病的情绪和认知症状及其最常见的合并症提供了新的可能性。