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Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

DOI: 10.1155/2011/762139

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Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript) has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART. 1. Introduction Depression or major depression disorder (MDD) is one of the most prevalent and debilitating public health concerns. MDD affects millions of people each year [1, 2], and the burden of this disease will continue to increase, especially during the extra years of life gained from improved health outcomes in cardiovascular disease, cancer, and other domains [3, 4]. Notably evidence showed that MDD affects more women than men [5]. According to the guidelines developed by the American Psychiatric Association, MDD can be diagnosed when a patient demonstrates at least 2 weeks of depressed mood or loss of interest accompanied by at least four additional symptoms, including constant sadness, irritability, hopelessness, trouble sleeping, low energy or fatigue, feeling worthless or guilty for no reason, significant weight change (gain or loss), difficulty concentrating, and loss of interest in favorite activities [5, 6]. However, the etiology and pathology of this serious biologic disease are still largely unknown. It is likely the result of a complex interaction of genetic, epigenetic, biochemical, environmental, and psychosocial factors. Now, there is compelling evidence that monoaminergic neurotransmission in the brain is disturbed in depressed patients. However, usually it takes between 1

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