RESUMEN
Social stress can contribute to the development of substance use disorders (SUDs) and increase the likelihood of relapse. Oxytocin (OT) is a potential pharmacotherapy that may buffer the effects of social stress on arousal and reward neurocircuitry. However, more research is needed to understand how OT moderates the brain's response to social stress in SUDs. The present study examined the effect of intransasal OT (24 IU) versus placebo (PBO) on corticolimbic functional connectivity associated with acute social stress in individuals with cocaine use disorder (CUD; n = 67) and healthy controls (HC; n = 52). Psychophysiological interaction modeling used the left and right amygdala as seed regions with the left and right orbitofrontal and anterior cingulate cortex as a priori regions of interest. Moderators of the OT response included childhood trauma history and biological sex, which were examined in independent analyses. The main finding was that OT normalized corticolimbic connectivity (left amygdala-orbitofrontal and left amygdala-anterior cingulate) as a function of childhood trauma such that connectivity was different between trauma-present and trauma-absent groups on PBO, but not between trauma groups on OT. Effects of OT on corticolimbic connectivity were not different as a function of diagnosis (CUD vs HC) or sex. However, OT reduced subjective anxiety during social stress for CUD participants who reported childhood trauma compared to PBO and normalized craving response as a function of sex in CUD. The present findings add to some prior findings of normalizing effects of OT on corticolimbic circuitry in individuals with trauma histories and provide some initial support that OT can normalize subjective anxiety and craving in CUD.
RESUMEN
BACKGROUND: Childhood socioeconomic disadvantage is a form of adversity associated with alterations in critical frontolimbic circuits involved in the pathophysiology of psychiatric disorders. Most work has focused on individual-level socioeconomic position, yet individuals living in deprived communities typically encounter additional environmental stressors that have unique effects on the brain and health outcomes. Notably, chronic and unpredictable stressors experienced in the everyday lives of youth living in disadvantaged neighborhoods may impact neural responsivity to uncertain threat. METHODS: A community sample of children (N = 254) ages 8 to 15 years (mean = 12.15) completed a picture anticipation task during a functional magnetic resonance imaging scan, during which neutral and negatively valenced photos were presented in a temporally predictable or unpredictable manner. Area Deprivation Index (ADI) scores were derived from participants' home addresses as an index of relative neighborhood disadvantage. Voxelwise analyses examined interactions of ADI, valence, and predictability on neural response to picture presentation. RESULTS: There was a significant ADI × valence interaction in the middle temporal gyrus, anterior cingulate cortex, hippocampus, and amygdala. Higher ADI was associated with less amygdala activation to negatively valenced images. ADI also interacted with predictability. Higher ADI was associated with greater activation of lingual and calcarine gyri for unpredictably presented stimuli. There was no three-way interaction of ADI, valence, and predictability. CONCLUSIONS: Neighborhood disadvantage may impact how the brain perceives and responds to potential threats. Future longitudinal work is critical for delineating how such effects may persist across the life span and how health outcomes may be modifiable with community-based interventions and policies.
