Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Anka Bernhard, Marietta Kirchner, Anne Martinelli, Katharina Ackermann, Gregor Kohls, Karen Gonzalez-Madruga, Amy Wells, Aranzazu Fernández-Rivas, Maider Gonzalez De Artaza-Lavesa, Nora Maria Raschle, Angeliki Konsta, Réka Siklósi, Amaia Hervás, Beate Herpertz-Dahlmann, Stephane A De Brito, Arne Popma, Christina Stadler, Kerstin Konrad, Graeme Fairchild, Christine M Freitag

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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.

Original languageEnglish
Pages (from-to)40-53
Number of pages14
JournalEuropean Neuropsychopharmacology
Early online date2 Apr 2021
Publication statusPublished - Aug 2021

Bibliographical note

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


  • Conduct disorder
  • Environmental risk factors
  • Neuropeptides
  • Sex differences
  • Steroid hormones

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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