TY - JOUR
T1 - Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system
AU - Catale, Clarissa
AU - Bussone, Silvia
AU - Lo Iacono, Luisa
AU - Viscomi, Maria Teresa
AU - Palacios, Daniela
AU - Troisi, Alfonso
AU - Carola, Valeria
N1 - Funding Information:
The authors thank patients, who participated in this study, and the staff of the outpatient clinic (Dr. Pietro Casella, Dr. Paola Di Sabato, and Dr. Alessandro Valzania) who facilitated the data collection. The professional editorial work of Blue Pencil Science is also acknowledged. This work was supported by the Italian Ministry of Health, Young Researcher Grant (number: GR-2009-1576820 ) and “2015-6 x mille” Grant , and by Sapienza University , 2019-Research Grant (number: RG11916B50652E41 ), to V.C. All authors reported no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the “translation” of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.
AB - The existence of a proportional relationship between the number of early-life stress (ELS) events experienced and the impoverishment of child mental health has been hypothesized. However, different types of ELS experiences may be associated with different neuro-psycho-biological impacts, due to differences in the intrinsic nature of the stress. DNA methylation is one of the molecular mechanisms that have been implicated in the “translation” of ELS exposure into neurobiological and behavioral abnormalities during adulthood. Here, we investigated whether different ELS experiences resulted in differential impacts on global DNA methylation levels in the brain and blood samples from mice and humans. ELS exposure in mice resulted in observable changes in adulthood, with exposure to social isolation inducing more dramatic alterations in global DNA methylation levels in several brain structures compared with exposure to a social threatening environment. Moreover, these two types of stress resulted in differential impacts on the epigenetic programming of different brain regions and cellular populations, namely microglia. In a pilot clinical study, blood global DNA methylation levels and exposure to childhood neglect or abuse were investigated in patients presenting with major depressive disorder or substance use disorder. A significant effect of the mental health diagnosis on global methylation levels was observed, but no effect of either childhood abuse or neglect was detected. These findings demonstrate that different types of ELS have differential impacts on epigenetic programming, through DNA methylation in specific brain regions, and that these differential impacts are associated with the different behavioral outcomes observed after ELS experiences.
KW - Blood
KW - Brain
KW - Childhood maltreatment
KW - Clinical psychology
KW - Early-life stress
KW - Epigenetics
KW - Global DNA methylation
KW - Major depression
KW - Substance use disorder
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U2 - 10.1016/j.ynstr.2020.100249
DO - 10.1016/j.ynstr.2020.100249
M3 - Article
AN - SCOPUS:85090724929
VL - 13
JO - Neurobiology of Stress
JF - Neurobiology of Stress
SN - 2352-2895
M1 - 100249
ER -