The BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene. Among 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions. This is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.

This study investigated internalizing problems, externalizing problems, and polydrug use among African-American youth residing in high-poverty neighborhoods, and tested the potential protective effects of religiosity, parental monitoring, and neighborhood collective efficacy on life stress and behavioral health outcomes (N = 576; 307 females; Mage = 16 years, SD = 1.44 years). A cumulative risk index reflected the combined effects of past year exposure to stressful life events, racial discrimination, and exposure to violence along with poor neighborhood ecology. Structural equation modeling revealed that cumulative risk significantly predicted internalizing problems, externalizing problems, and polydrug use. Interaction tests showed that the association of cumulative risk with internalizing problems was buffered by adolescent religiosity and neighborhood collective efficacy. The association of cumulative risk with externalizing problems was buffered by parental monitoring and collective efficacy. Adolescent sex further moderated these effects. The findings of the present study collectively highlight potential for protective factors to buffer effects of cumulative risk on behavioral health outcomes among youth residing in high-risk neighborhoods.

Comorbidity of internalizing and externalizing problems and its risk and protective factors have not been well incorporated into developmental research, especially among racial minority youth from high-poverty neighborhoods. The present study identified a latent comorbid factor as well as specific factors underlying internalizing and externalizing problems among 592 African American adolescents living in economically disadvantaged neighborhoods (291 male; M age = 15.9 years, SD = 1.43 years). Stressful life events and racial discrimination were associated with higher comorbid problems, whereas stressful life events and exposure to violence were associated with higher specific externalizing problems. Collective efficacy was associated with both lower specific externalizing problems and lower comorbid problems. Moreover, high collective efficacy buffered the risk effects of stressful life events and racial discrimination on comorbid problems. Our results demonstrated the advantages of latent variable modeling to understanding comorbidity by articulating impacts of risk factors on comorbid and specific components underlying internalizing and externalizing problems. They also highlighted the protective effect of collective efficacy in mitigating risks for these problems. These findings broadly call for more studies on comorbidities in developmental psychopathology among youth from diverse sociocultural backgrounds.