| Abstrakt: |
Introduction: Major depressive disorder (MDD) is a serious public health problem and one of the most common psychiatric disorders, with a lifetime prevalence of 17% in the United States and an estimated that 121 million people affected worldwide. Almost one million lives are lost yearly due to suicide, which translates to 3000 suicide deaths every day. Moreover, people suffering from severe depression have high rates of morbidity with profound economic and social consequences. Neuronal mTOR function is influenced by activity of growth factors, cytokines, and glutamate activity through NMDA and metabotropic receptors (mGluR), which have been reported to be involved with MDD. In addition, mTOR is associated with local protein synthesis and formation of new synapses. Bipolar Disorder: Bipolar disorder (BD) is a severe mood disorder characterized by recurrent episodes of mania followed by depression. Moreover, BD is associated with high morbidity, mortality, and risk of suicide. It has been shown that people suffering with BD die 10-20 years earlier than the general population. Exploration of mTOR pathway involvement in BD could open new opportunities for drug development. Strong evidence implicates intracellular signaling cascades dysfunction in the pathophysiology of Bipolar Disorder. Many of the individuals with BD in this study were treated with mood stabilizers and/or antidepressants. Rodrigo Machado-Vieira et al. found the expression of AKT and mTOR mRNA in peripheral blood decreased during a depressive episode in patients taking the mood stabilizer lithium as compared to healthy controls. Moreover, Raptor, the component of the mTORC1 protein complex, is associated with BD. Kara et al. confirmed that when the mTOR inhibitor, rapamycin and autophagy enhancers, temosirolimus were administered to animal models of mania and depression, rapamycin improved manic behaviour and termsirolimus improved depressive behavior. Anxiety: Anxiety is a common psychiatric disorder. Generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia are the most common types of anxiety. According to large population-based studies, up to 33.7% of people are affected by anxiety disorders during their lives. Genetic factors have a crucial role in the inclination to anxiety behaviors. Inhibition of mTOR signaling by genetic removal of p70S6 kinase 1 increased anxiety-like behavior in mice. Schizophrenia: Schizophrenia is another psychiatric disorder characterized with abnormal social behavior. Evidence which supports a role of disrupted mTOR signaling in the neuropathology of schizophrenia is based on a range of studies which have reported that dysfunction of diverse upstream activators and environmental stressors that have been previously implicated in schizophrenia can lead to either over-activation or inhibition of the signaling pathway. For example, the occurrence of schizophrenia in complex 1 deficiency, related to the gene disrupted in schizophrenia I (DISC1), results in an increase in pAkt and pS6. This has been shown in a DISC1 knockdown cell line in which rapamycin intervention attenuated biochemical and behavioral outcomes. Conclusion: It seems that, mTOR signaling is novel targets for the treatment of neuropsychiatric disorders such as anxiety, depression and schizophrenia. mTOR may be the solution for many unanswered questions about the pathophysiology of these diseases. [ABSTRACT FROM AUTHOR] |
