Childhood Trauma Moderates Inhibitory Control and Anterior Cingulate Cortex Activation during Anxiety Inducing Stressful Situations.

Introduction: Stress is a hallmark of heightened risk for addictive disorders, and exposure to distressing situations may trigger craving and anxiety, which contribute to substance use and relapse among patients. Additionally, childhood trauma contributes to greater sensitivity to stressful situations through persistent changes in the functioning of brain regions that process stress and emotion. However, inhibitory control may have important clinical implications in mitigating aversive reactions to stressful situations that may propagate maladaptive behaviors. While the anterior cingulate cortex (ACC) is a critical structure for both stress and inhibitory control processes, the impact of childhood trauma on ACC stress reactivity among individuals with varying levels of inhibitory control remains an important research gap. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence.

Method: Sixty-four adolescents (62% male) between ages 14-17 years (mean=14.8, sd=.94), were stratified into higher- or lower-childhood-trauma groups. Inhibitory control assessed between ages 7-9.5 years (mean = 7.6, sd=.8) was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging were used to probe the neural correlates of anxiety/motivational states in adolescents.

Results: Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, shown by previous meta-analysis to be associated with Stroop Color-Word task across multiple studies, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r=-.23, p=.04). Childhood-trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction=-1.26, p=.02, 95%CI=-2.33,-.20), where greater Stroop errors were associated with lower brain activation among those with higher-childhood-trauma (simple slopes=-.83, p=.007, 95%CI=-1.40,-.25). Lower stress-related rCZa activation was associated with greater subjective anxiety (baseline: R²=.19, b=-.43, p=.001, 95%CI=-4.11,-1.06; post-stress-cue: R²=.13, b=-.33, p=.02, 95%CI=-3.74,-.40), which persisted after controlling for childhood-trauma.

Conclusions: This is the first study to demonstrate the moderating role of childhood-trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood-trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate the relationships between childhood-trauma and addictive behaviors precipitated by stress.