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PI3K-AKT/mTOR signalling in psychiatric disorders: a valuable target to stimulate or suppress?

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as one of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious side effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signalling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signalling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signalling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signalling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.

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