The Effects of Prenatal Exposure to Neighborhood Crime on Neonatal Functional Connectivity Rebecca G. Brady, Cynthia E. Rogers, Trinidi Prochaska, Sydney Kaplan, Rachel E. Lean, Tara A. Smyser, Joshua S. Shimony, George M. Slavich, Barbara B. Warner, Deanna M. Barch, Joan L. Luby, and Christopher D. Smyser ABSTRACT BACKGROUND: Maternal exposure to adversity during pregnancy has been found to affect infant brain development; however, the specific effect of prenatal crime exposure on neonatal brain connectivity remains unclear. Based on existing research, we hypothesized that living in a high-crime neighborhood during pregnancy would affect neonatal frontolimbic connectivity over and above other individual- and neighborhood-level adversity and that these associations would be mediated by maternal psychosocial stress. METHODS: Participants included 399 pregnant women, recruited as part of the eLABE (Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders) study. In the neonatal period, 319 healthy, nonsedated infants were scanned using resting-state functional magnetic resonance imaging (repetition time = 800 ms; echo time = 37 ms; voxel size = 2.0 3 2.0 3 2.0 mm3 ; multiband = 8) on a Prisma 3T scanner and had at least 10 minutes of high-quality data. Crime data at the block group level were obtained from Applied Geographic Solution. Linear regressions and mediation models tested associations between crime, frontolimbic connectivity, and psychosocial stress. RESULTS: Living in a neighborhood with high property crime during pregnancy was related to weaker neonatal functional connectivity between the thalamus–anterior default mode network (aDMN) (b = 20.15, 95% CI = 20.25 to 20.04, p = .008). Similarly, high neighborhood violent crime was related to weaker functional connectivity between the thalamus-aDMN (b = 20.16, 95% CI = 20.29 to 20.04, p = .01) and amygdala-hippocampus (b = 20.16, 95% CI = 20.29 to 20.03, p = .02), controlling for other types of adversity. Psychosocial stress partially mediated relationships between the thalamus-aDMN and both violent and property crime. CONCLUSIONS: These findings suggest that prenatal exposure to crime is associated with weaker neonatal limbic and frontal functional brain connections, providing another reason for targeted public policy interventions to reduce crime. crucial time for fetal brain development, beginning with neural tube formation in the first 4 weeks after conception and progressing to the establishment of functional brain connectivity (1). Functional networks, albeit in an immature state, have been observed in the second and third trimesters of pregnancy in studies of fetuses and premature neonates (2–4). By the time of birth, the neonatal brain is organized into a collection of resting-state networks that include thalamocortical, interhemispheric, and intrahemispheric connections (5,6). Prior research has demonstrated associations between prenatal stressor exposure and later functional connectivity in offspring (7,8). Specifically, prenatal depression has been shown to alter connectivity between the amygdala and both subcortical and prefrontal areas (9–12). In addition, increases in the number of stressful life events during pregnancy has been associated with reduced amygdala– medial prefrontal cortex connectivity (13). These associations may be driven by stress- and inflammation-related mediators, including cytokines, tryptophan, catecholamines, and cortisol, which can cross the placenta (14). In fact, cortisol concentrations and interleukin 6 levels have been related to neonatal amygdala connectivity and subsequent psychiatric symptoms at age 24 months (15,16). Preclinical models also indicate that the hippocampus, in addition to the amygdala, is affected by prenatal stress and corticotropin-releasing hormone (17–20). Given the rapid brain development and sensitivity to stress in the prenatal period, neural development in utero may be especially vulnerable to various forms of individual and environmental adversity that increase maternal stress. However, it is unclear whether prenatal exposure to neighborhood crime ª 2022 Society of Biological Psychiatry. 1 www.sobp.org/journal Biological Psychiatry (i.e., levels of crime in a neighborhood even when an individual has not had a personal victimization experience) is a specific form of adversity associated with brain development over and above other stressors. It is plausible that neighborhood crime relates to brain function over and above direct violence exposure, similar to how neighborhood poverty relates to brain structure and function when controlling for personal income (21–23). Furthermore, neighborhood crime may have distinct effects from neighborhood poverty (or other socioeconomic adversity) based on conceptual models that