TY - JOUR
T1 - Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk
AU - Bernhard, Anka
AU - Kirchner, Marietta
AU - Martinelli, Anne
AU - Ackermann, Katharina
AU - Kohls, Gregor
AU - Gonzalez-Madruga, Karen
AU - Wells, Amy
AU - Fernández-Rivas, Aranzazu
AU - De Artaza-Lavesa, Maider Gonzalez
AU - Raschle, Nora Maria
AU - Konsta, Angeliki
AU - Siklósi, Réka
AU - Hervás, Amaia
AU - Herpertz-Dahlmann, Beate
AU - De Brito, Stephane A.
AU - Popma, Arne
AU - Stadler, Christina
AU - Konrad, Kerstin
AU - Fairchild, Graeme
AU - Freitag, Christine M.
N1 - Funding Information:
This study was funded by the European Commission's Seventh Framework Program (FP7 grant no. 602,407; FemNAT-CD). The European Commission had no further role in study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2021
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/31
Y1 - 2021/8/31
N2 - Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.
AB - Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.
KW - Conduct disorder
KW - Environmental risk factors
KW - FEMNAT-CD
KW - Neuropeptides
KW - Sex differences
KW - Steroid hormones
UR - http://www.scopus.com/inward/record.url?scp=85103639549&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2021.03.016
DO - 10.1016/j.euroneuro.2021.03.016
M3 - Article
C2 - 33813055
AN - SCOPUS:85103639549
SN - 0924-977X
VL - 49
SP - 40
EP - 53
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -
