PDF(Pubmed)
Abstract：
Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.
摘要：
尽管在理解精神疾病（PD）的病理生理学方面取得了重大进展，治疗进展并不令人信服。虽然精神药物可以减轻PD患者的经典症状，据报道，它们的长期使用会诱发或夸大各种预先存在的代谢异常，包括糖尿病，肥胖和非酒精性脂肪性肝病（NAFLD）。这些代谢异常的潜在机制尚不清楚；然而，脂质/脂肪酸积累由于增强的从头脂肪生成（DNL）已被证明会降低膜流动性，增加氧化应激和炎症导致上述代谢异常的发展。有趣的是，新的证据表明，DNL失调和脂肪酸积累可能是与肥胖发展相关的主要机制，PDs患者长期使用精神药物治疗后的糖尿病和NAFLD。为了支持这一点,几种辅助药物包括抗氧化剂和抗炎剂，用于与精神药物联合治疗PD，已被证明可以减少胰岛素抵抗和NAFLD的发展。总之,上述证据表明DNL可能是与多种代谢异常相关的潜在病理因素,以及PD中转化研究和治疗药物设计的新途径。
