Adversity in childhood and depression: linked through SIRT1.
Experiencing an adverse childhood and parental neglect is a risk factor for depression in the adult population. Patients with a history of traumatic childhood develop a subtype of depression that is characterized by earlier onset, poor treatment response and more severe symptoms. The long-lasting molecular mechanisms that are engaged during early traumatic events and determine the risk for depression are poorly understood. In this study, we altered adult depression-like behavior in mice by applying juvenile isolation stress. We found that this behavioral phenotype was associated with a reduction in the levels of the deacetylase sirtuin1 (SIRT1) in the brain and in peripheral blood mononuclear cells. Notably, peripheral blood mRNA expression of SIRT1 predicted the extent of behavioral despair only when depression-like behavior was induced by juvenile--but not adult--stress, implicating SIRT1 in the regulation of adult behavior at early ages. Consistent with this hypothesis, pharmacological modulation of SIRT1 during juvenile age altered the depression-like behavior in naive mice. We also performed a pilot study in humans, in which the blood levels of SIRT1 correlated significantly with the severity of symptoms in major depression patients, especially in those who received less parental care during childhood. On the basis of these novel findings, we propose the involvement of SIRT1 in the long-term consequences of adverse childhood experiences.
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.
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Lo Iacono
Department of Physiology and Pharmacology, University of Rome 'La Sapienza,' Rome, Italy.
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Visco-Comandini
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.
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Valzania
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.
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Viscomi
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Coviello
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Giampà
Department of Psychology and 'Daniel Bovet' Center, University of Rome 'La Sapienza,' Rome, Italy.
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Roscini
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.
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Bisicchia
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Siracusano
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Troisi
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.|Department of Psychology and 'Daniel Bovet' Center, University of Rome 'La Sapienza,' Rome, Italy.
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Puglisi-Allegra
Department of Experimental Neurosciences, IRCSS Fondazione Santa Lucia, Rome, Italy.
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Carola
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012307:Risk Factors; D056564:Sirtuin 1 / Q000378:metabolism*; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
D056564:Sirtuin 1