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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Anka Bernhard - , Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Frankfurt (Author)
  • Marietta Kirchner - , University Hospital Heidelberg (Author)
  • Anne Martinelli - , University Hospital Frankfurt (Author)
  • Katharina Ackermann - , University Hospital Frankfurt (Author)
  • Gregor Kohls - , Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Aachen (Author)
  • Karen Gonzalez-Madruga - , University of Southampton (Author)
  • Amy Wells - , Cardiff University (Author)
  • Aranzazu Fernández-Rivas - , Hospital de Basurto (Author)
  • Maider Gonzalez De Artaza-Lavesa - , Hospital de Basurto (Author)
  • Nora Maria Raschle - , University Psychiatric Clinics Basel (UPK) (Author)
  • Angeliki Konsta - , National and Kapodistrian University of Athens (Author)
  • Réka Siklósi - , University of Szeged (Author)
  • Amaia Hervás - , University Hospital Mutua Terrassa (Author)
  • Beate Herpertz-Dahlmann - , University Hospital Aachen (Author)
  • Stephane A De Brito - , University of Alabama at Birmingham (Author)
  • Arne Popma - , Amsterdam University Medical Centers (UMC) (Author)
  • Christina Stadler - , University Psychiatric Clinics Basel (UPK) (Author)
  • Kerstin Konrad - , University Hospital Aachen (Author)
  • Graeme Fairchild - , University of Bath (Author)
  • Christine M Freitag - , University Hospital Frankfurt (Author)


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
Publication statusPublished - Aug 2021

External IDs

Scopus 85103639549



  • Adolescent, Biomarkers, Conduct Disorder, Dehydroepiandrosterone, Estradiol, Female, Gonadal Steroid Hormones, Humans, Hydrocortisone, Male, Neuropeptides, Neurosecretory Systems, Oxytocin, Progesterone, Steroids, Testosterone, alpha-Amylases