Citation

Werhahn JE, Smigielski L, Sacu S, Mohl S, Willinger D, Naaijen J, Mulder LM, Glennon JC, Hoekstra PJ, Dietrich A, Deters RK, Aggensteiner PM, Holz NE, Baumeister S, Banaschewski T, Saam MC, Schulze UME, Lythgoe DJ, Sethi A, Craig M, Mastroianni M, Sagar-Ouriaghli I, Santosh PJ, Rosa M, Bargalló N, Castro-Fornieles J, Arango C, Penzol MJ, Zwiers MP, Franke B, Buitelaar JK, Walitza S, Brandeis D. Neuroimage (Amst) 2023; 40: e103542.

Copyright

(Copyright © 2023, Elsevier Publishing)

DOI

10.1016/j.nicl.2023.103542

PMID

37988996

Abstract

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities.

METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla.

RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for.

CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

Language: en

Keywords

Children; Adolescents; Callous-unemotional traits; Proactive aggression; Reactive aggression; Resting-state fMRI