Potentially traumatic events and substance use do not predict changes in resting state functional connectivity in early adolescence

• Combined trauma and substance use impacts on youth resting state are understudied • A longitudinal study assessing within-youth connectivity changes addresses the issue • Within-youth regressions of longitudinal data provide a more robust association • Neither trauma or substance use affect adolescent large-scale network functional connectivity • Resting-state connectivity fails to detect youth at risk for co-occurring PTSD and SUD Potentially traumatic events (PTEs) and substance use (SU) are commonly endorsed in early adolescence, a crucial period for neurodevelopment. PTEs and SU are precipitating events in the etiological development of comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Separately, they have been shown to alter within- and between-network connectivity in the three brain networks posited by Menon’s Theory of Psychopathology: the default mode network (DMN), fronto-parietal network (FPN), and salience network (SN). While comorbid PTSD+SUD in adulthood shows shared neural underpinnings, this is less clear in adolescence. We analyzed the effects of PTEs and SU on resting state functional connectivity (rsFC) in 9-15 year olds from the Adolescent Brain Cognitive Development (ABCD) Study. Fixed effects panel models were fit to assess the effects of PTEs and SU on between-network (FPN-SN rsFC, DMN-SN rsFC, and FPN-DMN rsFC) and within-network (FPN rsFC, SN rsFC, and DMN rsFC) connectivity measured across three timepoints spanning two years. PTEs, SU, and their interaction was not significantly associated with between- and within-network rsFC two years later. No sex specific interactions were observed. Results suggest rsFC changes observed in older adolescents and adults with comorbid PTSD+SUD do not developmentally translate to early adolescents endorsing PTEs+SU. Lack of impact on rsFC may indicate a potential buffer period in which PTEs and SU do not affect rsFC until later in development or after symptom onset following PTEs+SU.