Neural correlates of emotion regulation causally mediate parenting effects on adolescent internalising symptoms

Introduction: Adolescence is a period of heightened vulnerability to internalising symptoms, such as depression and anxiety, especially in girls (Dahl et al., 2018). Developmental models suggest that significant reorganisation of neural systems involved in emotion regulation may contribute to this vulnerability (Casey et al., 2008). At the same time, the adolescent brain is sensitive to environmental inputs, with evidence suggesting that parenting behaviours influence the neural correlates of emotion regulation and the development of internalising outcomes in young people (Kerr et al., 2019; Yap et al., 2014). However, no study has yet examined whether a causal relationship exists between parenting and brain function, and whether brain function acts as a mediating mechanism through which parenting influences adolescent internalising outcomes. Methods: Female adolescents with elevated internalising symptoms (N = 70, mean age, 11.46 [SD = 0.77]) and their mothers were randomly assigned to an emotion-focused parenting intervention (Tuning in to Teens [TINT; Havighurst et al., 2019], N = 34) or a waitlist control group (N = 36). At baseline and 6-month follow-up, adolescents underwent fMRI scans during implicit and explicit emotion regulation (i.e., affect labelling task, cognitive reappraisal task). We used voxel-wise repeated measures ANOVA implemented in SPM to examine the interaction effect of a between-subject factor of group (intervention vs control) and a within-subject factor of time (baseline vs 6-month follow-up) on adolescent brain activation and functional connectivity during emotion regulation tasks. For brain activation, we conducted both amygdala and prefrontal cortex region of interest (ROI) analysis and exploratory whole-brain analysis. Whole brain functional connectivity was assessed with generalised psychophysiological interaction analysis, including the amygdala, insula, and hippocampus as seed regions. The BOLD signal from significant clusters from the repeated measure ANOVA (mean of signal from a 5mm radius sphere around peak values) was extracted for causal mediation analysis. Adolescent internalising symptoms were assessed using the Revised Children’s Anxiety and Depressions Scale at baseline and 8-month follow-up. We used a model-based inference approach with the ‘mediation’ package (Tingley et al., 2014) implemented in R to examine causal effects of the TINT intervention on adolescent internalising symptoms through brain function (controlling for baseline adolescent symptoms and brain function). Point estimates for the average causal mediation effect (ACME) with 95% CI using 1000 bootstrapped Monte Carlo simulations were calculated. Results: Adolescent girls whose mothers received the TINT intervention (as compared to the control condition) showed increased activation in the superior frontal gyrus (SFG) during affect labelling and decreased activation in the inferior frontal gyrus (IFG) during cognitive reappraisal. Additionally, adolescents from the intervention group relative to the control group showed greater insula-supplementary motor area and insula-precuneus functional connectivity during cognitive reappraisal. Causal mediation analysis showed that the IFG activity at 6-month follow-up partly explained the effect of TINT on adolescent self-reported internalising symptoms at 8-month follow-up (ACME = -6.71, 95% CI = [-15.96, -0.63]). Conclusions: This study provides the first causal evidence that an emotion-focused parenting intervention altered neural correlates of emotion regulation in adolescent girls. Importantly, our findings identify neural mechanisms through which improvements in parenting lead to reductions in adolescent internalising symptoms, in a sample of early adolescent girls with elevated internalising symptoms. These findings suggest early adolescence may be a key window of intervention and highlight the importance of intervening with modifiable parenting behaviours to promote adaptive neural function and improve mental health in youth.