Signaling molecules and callous-unemotional traits in young people: A systematic review and methodological and future considerations

Natalie Goulter, Silvana Kaouar, Eva R. Kimonis

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Abstract

Burgeoning evidence supports multiple developmental pathways to antisocial behavior. However, a comprehensive mechanistic understanding is lacking, and insights into the development of different presentations might be gained by investigating concentration levels of signaling molecules from physiological systems related to socioaffective functioning and adverse experiences. Thus, we aimed to systematically review correlates of all signaling molecules currently examined in the literature in relation to callous-unemotional (CU) traits (and the affective dimension of psychopathy) in samples of young people (≤18 years old). Given established variability in physiological activity across developmental stage and biological sex, we further aimed to assess evidence of developmental stages and sex differences. Finally, we aimed to analyze methodologies applied to test molecule levels. In total, we identified 32 articles for summary, across which seven distinct molecules were identified: cortisol, testosterone, oxytocin, dehydroepiandrosterone, estradiol, α-amylase, and C-reactive protein. Overall, findings were mixed including for cortisol that was the most widely studied molecule. Studies used a wide variety of methodological approaches, with scant research on inflammatory markers. We discuss how two key factors might contribute to the lack of clarity: diverse conceptualization of adversity (e.g., acute v. chronic, proximate v. distal) across studies, and limited consideration of primary and secondary variants of CU/psychopathic traits that are expected to show opposing physiological patterns. Best methodological practices are offered, and implications of findings for informing CU theory, future research, and intervention efforts are discussed.

Original languageEnglish
Article number106259
Number of pages21
JournalNEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume176
DOIs
Publication statusPublished - Sept 2025

Keywords

  • Autonomic nervous system
  • Callous-unemotional
  • Hypothalamic-pituitary-adrenal
  • Hypothalamic-pituitary-gonadal
  • Inflammation
  • Neurohypophysial peptide
  • Psychopathy

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