Adversity in childhood and depression: linked through SIRT1

Abstract

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.

Social threat exposure in juvenile mice promotes cocaine‐seeking by altering blood clotting and brain vasculature

“…The two experiences likely involve disparate structures of the brain and differentially affect long‐term biological mechanisms. Consistent with this possibility, the long‐term behavioral effects in NS‐S and S‐S mice diverge in adulthood toward a depression‐like phenotype (Lo Iacono et al ) and increased cocaine‐seeking behavior, respectively (Fig. c).…”

Peripheral blood microRNAandVEGFAmRNAchanges following electroconvulsive therapy: implications for psychotic depression

“…ECS results in increased levels of SIRT1 in the hypothalamus and hippocampus . There is a growing support for a role of SIRT1 in depression . The further study of these gene targets would therefore be of interest, and we intend to follow‐up both SIRT1 and E2F1 in further studies in the same cohort.…”

Genome‐wide association study of periweaning failure‐to‐thrive syndrome (PFTS) in pigs

“…Further investigation of these two regions using a haplotype test with a backward elimination process on SSC14 reinforced the importance of these genomic regions on the appearance of PFTS. These two regions on SSC14 harbours 15 positional candidate genes (Table 2), some of them related to neurological disorders in humans, such as TSNAX (translin-associated factor X) (Arias and others 2014) , GNPAT (glyceronephosphate O-acyltransferase) (Buchert and others 2014) , ARV1 (ARV1 homologue) (Alazami and others 2015), EGR2 (early growth response 2) (Vrebalov Cindro and Vrebalov Cindro 2015), and SIRT1 (sirtuin 1) (Lo Iacono and others 2015). …”