Advances in Stem Cells Biology: New Approaches to Understand Depression
Depression is a highly prevalent complex neuropsychiatric disorder, which ranks first among all mental and neurological disorders as a contributor to the global burden of disease. However, available treatments are still far from ideal, for their specifici
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Abstract Depression is a highly prevalent complex neuropsychiatric disorder, which ranks first among all mental and neurological disorders as a contributor to the global burden of disease. However, available treatments are still far from ideal, for their specificity as well as their efficacy. This situation can now be improved by the increasing availability of stem cells, which allows the development of in vitro human neural systems to model the brain. These models complement observations from animal models and patients with depression, allowing for a better understanding of the complexity of this psychiatric illness and potential treatments. Cells derived from the olfactory neuroepithelium, multipotent fetal hippocampal progenitor cells (HPCs) and human induced pluripotent stem cells (iPSCs) have shown promising leads. Using HPCs and iPSC-derived forebrain neurons, we managed to provide further insights into the action of drugs with antidepressant action as well as on molecular mechanisms underlying the effect of stress and inflammation, both linked to the pathophysiology of depression. Particular attention has been paid to the complex pathways by which the immune and stress systems differently determine the final developmental fate of HPCs and the synaptic plasticity of iPSCs. The combination of accessibility and validity of the available stem cells models will allow further work to increase our insights into the biology of depression and support the identification of novel therapeutic targets.
Introduction How Can We Best Study Depression? Depression ranks first among all mental and neurological disorders as a contributor to the global burden of disease and causes a heavy load on patients and their
A. Borsini • P.A. Zunszain (*) Department of Psychological Medicine, Section of Stress, Psychiatry and Immunology, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK e-mail: [email protected] © The Author(s) 2016 D. Pfaff, Y. Christen (eds.), Stem Cells in Neuroendocrinology, Research and Perspectives in Endocrine Interactions, DOI 10.1007/978-3-319-41603-8_10
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families. However, available treatments are far from ideal. Only a third of patients respond to the initial treatment, another third will get better only after several changes of medication and the rest will go on to be treatment resistant (Rapaport et al. 2003; Trivedi et al. 2006). Why is this? We still do not know why depression happens; neither do we clearly understand how antidepressants work. Much of the current understanding about the pathogenesis of major depression has come from animal models (Krishnan and Nestler 2011) as well as from peripheral (Felger et al. 2012) and central nervous system (CNS; Raison et al. 2010) circulating measurements from patients with depression. Due to the unique and complex features of human depression, the generation of valid and more insightful depression models has been less straightforward than modeling other disabling diseases (K
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