The impact of potentially traumatic events and substance use on resting state functional connectivity in early adolescence

Background. Potentially traumatic events (PTEs) and substance use (SU) are commonly endorsed in early adolescence, a crucial period for neurodevelopment. Separately, they have been shown to alter within- and between- network connectivity in the three brain networks posited by Menon’s Theory of Psychopathology to give rise to psychopathological symptoms: default mode network (DMN), fronto-parietal network (FPN), and the salience network (SN). While co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) are known to have shared neural underpinnings in adults, how co-occurring PTEs and SU in adolescents impact the three main functional networks has yet to be examined. Methods. We analyzed the effects of PTEs and SU on multiple resting state functional connectivity (rsFC) outcomes in 9-15 year old youth from the Adolescent Brain Cognitive Development (ABCD) Study. Fixed effects panel models were fit to assess the effects of PTEs and SU on three between-network outcome variables (FPN-SN rsFC, DMN-SN rsFC, and FPN-DMN rsFC) and three within-network outcome variables (FPN rsFC, SN rsFC, and DMN rsFC) measured two years later, across three timepoints. Results. PTEs and SU independently predicted rsFC, such that PTEs independently predicted increased between-network FPN-SN (𝛽 = 0.00092, p<0.05) and DMN-SN (𝛽 = 0.00101, p<0.01) rsFC, while SU independently predicted increased within-network SN (𝛽 = 0.01724, p<0.05) rsFC. Other associations between PTEs or SU and network rsFC were confounded by age. In sex-specific models, we found all female effects were confounded by age, however, results from our primary models remained present in males.Conclusion. In our study, we failed to find evidence for the interaction of PTEs and SU significantly predicting between- or within- network rsFC outcomes. Though we found some support for PTEs and SU independently predicting between- and within-network connectivity. Though, age and sex confounded these relationships where results held for males but not females. Taken together, these results suggest that rsFC changes observed in older adolescents and adults with comorbid PTSD+SUD do not developmentally translate to early adolescents endorsing PTEs+SU. Thus, rsFC changes following PTEs+SU may not serve as an early onset biomarker for identifying youth most at risk for developing comorbid PTSD+SUD.