Childhood insulin resistance and neural stem cell dysfunction in psychiatric disorders: Role of lipogenesis and treatment perspectives.

Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells (NSCs). However, insulin resistance (IR) is associated with impaired NSC proliferation and cognitive dysfunction, which are the hallmarks of psychiatric disorders (PDs). In addition to insulin, lipogenesis (DNL) also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling. However, enhanced DNL is associated with lipid/fatty acid accumulation, IR, and impaired NSC proliferation. Intriguingly, data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs. Further, evidence suggests that patients with PDs may develop IR during childhood or before adolescence; therefore, DNL could be enhanced preceding the development of IR. Regarding treatment, while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL, various adjunctive drugs/therapies, including chemical, physical, and stem cell therapy, which have shown promising success in treating PDs, reduce DNL while enhancing insulin sensitivity, NSC proliferation, and cognitive function in laboratory animals. Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies, especially stem cell therapy in treating PDs including schizophrenia and depression, are discussed.