This review explores the role of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders, particularly depression, epilepsy, and schizophrenia. The mTOR pathway is a critical regulator of cell growth, metabolism, and neurodevelopment, and its dysfunction is associated with various neurological and psychotic disorders. The review highlights the following key points: 1. **Epidemiology and Pathogenesis**: Psychiatric disorders, including depression, anxiety, schizophrenia, and epilepsy, are prevalent global health issues. Chronic stress, genetic factors, and environmental influences contribute to their development. Clinical treatments include psychotherapy, chemotherapy, and electroconvulsive therapy, but adverse effects and resistance to antipsychotics remain significant challenges. 2. **mTOR Signaling in Psychiatric Disorders**: - **Depression**: Abnormal mTOR signaling is linked to impaired neurogenesis and neuroplasticity. Preclinical studies show that activating or enhancing mTOR signaling can have antidepressant effects. For example, crocin treatment increased mTOR phosphorylation and reduced depressive behavior in mice. - **Epilepsy**: mTOR signaling is hyperactivated during epileptogenesis, contributing to neuronal excitability and seizures. Inhibiting mTOR signaling with drugs like rapamycin reduces seizure intensity and frequency in animal models. - **Schizophrenia**: Disrupted mTOR signaling is associated with abnormal neuronal morphology and impaired synaptic plasticity. Studies suggest that downregulated mTOR signaling may contribute to the pathophysiology of schizophrenia, but the role is still controversial. 3. **Antipsychotic Drugs and mTOR Signaling**: - **Antidepressants**: Some antidepressants, such as ketamine, escitalopram, and paroxetine, exert their effects through the activation of the mTOR pathway. For instance, ketamine's rapid antidepressant effects are linked to the activation of AMPAR and BDNF, which in turn activate the mTOR pathway. - **Antiepileptic Drugs**: mTOR inhibitors like rapamycin have antiepileptic effects, reducing neuronal excitability and seizures in patients with epilepsy. - **Antipsychotics**: Antipsychotic drugs like aripiprazole and sertindole improve symptoms in animal models of schizophrenia by activating the PI3K/AKT/mTOR signaling pathway. 4. **Future Prospects**: - The review emphasizes the potential of mTOR signaling as a therapeutic target for psychiatric disorders. Understanding the molecular mechanisms underlying mTOR signaling may lead to the development of novel drugs that modulate this pathway to treat these conditions. - However, challenges remain, including the side effects of mTOR inhibitors, such as hepatotoxicity and pneumonitis, which need further research to optimize their use in clinical settings. In conclusion, the review underscores the importance of mTOR signaling in psychiatric disorders and its potential as a therapeutic target. Further research is needed to fully understand the mechanisms and develop effective treatments.This review explores the role of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders, particularly depression, epilepsy, and schizophrenia. The mTOR pathway is a critical regulator of cell growth, metabolism, and neurodevelopment, and its dysfunction is associated with various neurological and psychotic disorders. The review highlights the following key points: 1. **Epidemiology and Pathogenesis**: Psychiatric disorders, including depression, anxiety, schizophrenia, and epilepsy, are prevalent global health issues. Chronic stress, genetic factors, and environmental influences contribute to their development. Clinical treatments include psychotherapy, chemotherapy, and electroconvulsive therapy, but adverse effects and resistance to antipsychotics remain significant challenges. 2. **mTOR Signaling in Psychiatric Disorders**: - **Depression**: Abnormal mTOR signaling is linked to impaired neurogenesis and neuroplasticity. Preclinical studies show that activating or enhancing mTOR signaling can have antidepressant effects. For example, crocin treatment increased mTOR phosphorylation and reduced depressive behavior in mice. - **Epilepsy**: mTOR signaling is hyperactivated during epileptogenesis, contributing to neuronal excitability and seizures. Inhibiting mTOR signaling with drugs like rapamycin reduces seizure intensity and frequency in animal models. - **Schizophrenia**: Disrupted mTOR signaling is associated with abnormal neuronal morphology and impaired synaptic plasticity. Studies suggest that downregulated mTOR signaling may contribute to the pathophysiology of schizophrenia, but the role is still controversial. 3. **Antipsychotic Drugs and mTOR Signaling**: - **Antidepressants**: Some antidepressants, such as ketamine, escitalopram, and paroxetine, exert their effects through the activation of the mTOR pathway. For instance, ketamine's rapid antidepressant effects are linked to the activation of AMPAR and BDNF, which in turn activate the mTOR pathway. - **Antiepileptic Drugs**: mTOR inhibitors like rapamycin have antiepileptic effects, reducing neuronal excitability and seizures in patients with epilepsy. - **Antipsychotics**: Antipsychotic drugs like aripiprazole and sertindole improve symptoms in animal models of schizophrenia by activating the PI3K/AKT/mTOR signaling pathway. 4. **Future Prospects**: - The review emphasizes the potential of mTOR signaling as a therapeutic target for psychiatric disorders. Understanding the molecular mechanisms underlying mTOR signaling may lead to the development of novel drugs that modulate this pathway to treat these conditions. - However, challenges remain, including the side effects of mTOR inhibitors, such as hepatotoxicity and pneumonitis, which need further research to optimize their use in clinical settings. In conclusion, the review underscores the importance of mTOR signaling in psychiatric disorders and its potential as a therapeutic target. Further research is needed to fully understand the mechanisms and develop effective treatments.