TY - JOUR
T1 - Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood
T2 - a longitudinal genetically informed twin study
AU - Iob, Eleonora
AU - Baldwin, Jessie R
AU - Plomin, Robert
AU - Steptoe, Andrew
N1 - Funding Information:
Eleonora Iob is funded by the ESRC-BBSRC Soc-B Centre for Doctoral Training (ES/ P000347/1). Jessie R. Baldwin is funded by a Wellcome Trust Sir Henry Wellcome fellowship (grant 215917/Z/19/Z). Robert Plomin is supported by a Medical Research Council Professorship award (G19/2). We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. TEDS is supported by a programme grant to Robert Plomin from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). All authors contributed significantly to the conception, design, analysis or interpretation of data and were involved in revising it critically for intellectual context. The final submission of this paper was approved by all authors.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/5
Y1 - 2021/8/5
N2 - Dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3-11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = -0.20, p = 0.03), bullying (b = -0.61, p = 0.01), and emotional abuse (b = -0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = -0.56, p = 0.05). Lower cortisol levels mediated around 10-20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02-0.34]) and bullying (b = 0.18 [0.01-0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.
AB - Dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3-11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = -0.20, p = 0.03), bullying (b = -0.61, p = 0.01), and emotional abuse (b = -0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = -0.56, p = 0.05). Lower cortisol levels mediated around 10-20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02-0.34]) and bullying (b = 0.18 [0.01-0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.
KW - Adolescent
KW - Adult
KW - Adverse Childhood Experiences
KW - Child
KW - Child, Preschool
KW - Depression/genetics
KW - Humans
KW - Hydrocortisone
KW - Hypothalamo-Hypophyseal System
KW - Pituitary-Adrenal System
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85112009599&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01538-w
DO - 10.1038/s41398-021-01538-w
M3 - Article
C2 - 34354040
AN - SCOPUS:85112009599
SN - 2158-3188
VL - 11
SP - 420
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 420
ER -
