Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits

Stephane A. De Brito; Jack C. Rogers; Ruth Pauli; Gregor Kohls; Nora M. Raschle; Anne Martinelli; Areti Smaragdi; Karen Gonzalez-Madruga; Harriet Cornwell; Christina Stadler; Kerstin Konrad; Christine M. Freitag; Graeme Fairchild

doi:10.1016/j.biopsych.2025.04.023

Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits

Stephane A. De Brito, Jack C. Rogers, Ruth Pauli, Gregor Kohls, Nora M. Raschle, Anne Martinelli, Areti Smaragdi, Karen Gonzalez-Madruga, Harriet Cornwell, Christina Stadler, Kerstin Konrad, Christine M. Freitag, Graeme Fairchild

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Abstract

Background: Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits.

Methods: Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions.

Results: When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females < TD females; CD/LCU males > TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males).

Conclusions: The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.

Original language	English
Journal	Biological Psychiatry
Early online date	7 May 2025
DOIs	https://doi.org/10.1016/j.biopsych.2025.04.023
Publication status	E-pub ahead of print - 7 May 2025

Acknowledgements

We thank Ronald Limprecht, Institute of Medical Biometrie Heidelberg, who established and maintained the phenotypic database. We sincerely thank our participants and their families for taking part in the study and the other members of the FemNAT-CD consortium.

Funding

This work was supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration (Grant No. 602407) (FemNAT-CD; coordinator, CMF). During the preparation of the article, SADB was supported by a short-term Invitational Fellowship from the Japanese Society for the Promotion of Science (Grant No. S19103), an International Academic Fellowship from the Leverhulme Trust (Grant No. IAF-2019-032), and a project grant from the Economic and Social Research Council (Grant No. ES/V003526/1). GF was supported by a project grant from the Medical Research Council (Grant No. MR/T002816/1). GK was supported by a 2023 NARSAD Young Investigator grant from the Brain & Behavior Research Foundation (Grant No. 30849). NMR was supported by the Swiss National Science Foundation (Grant No. 105314_207624), Hochschulmedizin Zürich, and the University of Zurich Research Priority Program “Adaptive Brain Circuits in Development and Learning.” The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; or the decision to submit the article for publication.

Funders	Funder number
Economic and Social Research Council

Keywords

Callous-unemotional traits
Conduct disorder
Emotion processing
FemNAT-CD
fMRI
Sex differences

ASJC Scopus subject areas

Biological Psychiatry

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De Brito, S. A., Rogers, J. C., Pauli, R., Kohls, G., Raschle, N. M., Martinelli, A., Smaragdi, A., Gonzalez-Madruga, K., Cornwell, H., Stadler, C., Konrad, K., Freitag, C. M., & Fairchild, G. (2025). Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits. Biological Psychiatry. Advance online publication. https://doi.org/10.1016/j.biopsych.2025.04.023

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title = "Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits",

abstract = "Background: Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits. Methods: Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions. Results: When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females < TD females; CD/LCU males > TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males). Conclusions: The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.",

keywords = "Callous-unemotional traits, Conduct disorder, Emotion processing, FemNAT-CD, fMRI, Sex differences",

author = "\{De Brito\}, \{Stephane A.\} and Rogers, \{Jack C.\} and Ruth Pauli and Gregor Kohls and Raschle, \{Nora M.\} and Anne Martinelli and Areti Smaragdi and Karen Gonzalez-Madruga and Harriet Cornwell and Christina Stadler and Kerstin Konrad and Freitag, \{Christine M.\} and Graeme Fairchild",

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AU - De Brito, Stephane A.

AU - Rogers, Jack C.

AU - Pauli, Ruth

AU - Kohls, Gregor

AU - Raschle, Nora M.

AU - Martinelli, Anne

AU - Smaragdi, Areti

AU - Gonzalez-Madruga, Karen

AU - Cornwell, Harriet

AU - Stadler, Christina

AU - Konrad, Kerstin

AU - Freitag, Christine M.

AU - Fairchild, Graeme

PY - 2025/5/7

Y1 - 2025/5/7

N2 - Background: Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits. Methods: Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions. Results: When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females < TD females; CD/LCU males > TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males). Conclusions: The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.

AB - Background: Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits. Methods: Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions. Results: When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females < TD females; CD/LCU males > TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males). Conclusions: The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.

KW - Callous-unemotional traits

KW - Conduct disorder

KW - Emotion processing

KW - FemNAT-CD

KW - fMRI

KW - Sex differences

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JF - Biological Psychiatry

ER -

Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits

Abstract

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

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