Stage 2 Registered Report: The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach

Objective Youth with symptoms of emotion dysregulation are at risk for a multitude of psychiatric diagnoses later in life. However, few studies have focused on the underlying neurobiology of emotion dysregulation. This study assessed the bidirectional relationship between emotion dysregulation symptoms and brain morphology throughout childhood and adolescence. Method A combined total of 8,235 children and adolescents drawn from 2 large population-based cohorts, the Generation R Study and Adolescent Brain Cognitive Development (ABCD) Study, were included. Data were acquired in 3 waves in Generation R (mean [SD] age = 7.8 [1.0] wave 1 [W1]; 10.1 [0.6] W2; 13.9 [0.5] W3) and in 2 waves in ABCD (mean [SD] age = 9.9 [0.6] W1; 11.9 [0.6] W2). Cross-lagged panel models were used to determine the bidirectional relationships between emotion dysregulation symptoms and brain morphology. The study was preregistered before performing analyses. Results In the Generation R sample, emotion dysregulation symptoms at W1 preceded lower hippocampal (β = −.07, SE = 0.03, p = .017) and temporal pole (β = −.19, SE = 0.07, p = .006) volumes at W2. Emotion dysregulation symptoms at W2 preceded lower fractional anisotropy in the uncinate fasciculus (β = −.11, SE = 0.05, p = .017) and corticospinal tract (β = −.12, SE = 0.05, p = .012). In the ABCD sample, emotion dysregulation symptoms preceded posterior cingulate (β = .01, SE = 0.003, p = .014) and nucleus accumbens volumes (left hemisphere: β = −.02, SE = 0.01, p = .014; right hemisphere: β = −.02, SE = 0.01, p = .003). Conclusion In population-based samples, with relatively low psychopathology symptoms in the majority of children, symptoms of emotion dysregulation can precede differential development of brain morphology. This provides the foundation for future work to assess to what extent optimal brain development can be promoted through early intervention. Study registration information The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach; https://doi.org/10.1016/j.jaac.2022.03.008. Diversity & Inclusion Statement We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Youth with symptoms of emotion dysregulation are at risk for a multitude of psychiatric diagnoses later in life. However, few studies have focused on the underlying neurobiology of emotion dysregulation. This study assessed the bidirectional relationship between emotion dysregulation symptoms and brain morphology throughout childhood and adolescence. A combined total of 8,235 children and adolescents drawn from 2 large population-based cohorts, the Generation R Study and Adolescent Brain Cognitive Development (ABCD) Study, were included. Data were acquired in 3 waves in Generation R (mean [SD] age = 7.8 [1.0] wave 1 [W1]; 10.1 [0.6] W2; 13.9 [0.5] W3) and in 2 waves in ABCD (mean [SD] age = 9.9 [0.6] W1; 11.9 [0.6] W2). Cross-lagged panel models were used to determine the bidirectional relationships between emotion dysregulation symptoms and brain morphology. The study was preregistered before performing analyses. In the Generation R sample, emotion dysregulation symptoms at W1 preceded lower hippocampal (β = −.07, SE = 0.03, p = .017) and temporal pole (β = −.19, SE = 0.07, p = .006) volumes at W2. Emotion dysregulation symptoms at W2 preceded lower fractional anisotropy in the uncinate fasciculus (β = −.11, SE = 0.05, p = .017) and corticospinal tract (β = −.12, SE = 0.05, p = .012). In the ABCD sample, emotion dysregulation symptoms preceded posterior cingulate (β = .01, SE = 0.003, p = .014) and nucleus accumbens volumes (left hemisphere: β = −.02, SE = 0.01, p = .014; right hemisphere: β = −.02, SE = 0.01, p = .003). In population-based samples, with relatively low psychopathology symptoms in the majority of children, symptoms of emotion dysregulation can precede differential development of brain morphology. This provides the foundation for future work to assess to what extent optimal brain development can be promoted through early intervention.