Literature on neighborhood effects on health largely employs non-experimental study designs and does not typically test specific neighborhood mediators that influence health. We address these gaps using the Moving to Opportunity (MTO) housing voucher experiment. Research has documented both beneficial and adverse effects on health in MTO, but mediating mechanisms have not been tested explicitly. We tested mediation of MTO effects on youth asthma (n = 2829). MTO randomized families living in public housing to an experimental group receiving a voucher to subsidize rental housing, or a control group receiving no voucher, and measured outcomes 4-7 years following randomization. MTO had a harmful main effect vs. controls for self-reported asthma diagnosis (b = 0.24, p = 0.06), past-year asthma attack (b = 0.44, p = 0.02), and past-year wheezing (b = 0.17, p = 0.17). Using Inverse Odds Weighting mediation we tested mental health, smoking, and four housing dimensions as potential mediators of the MTO-asthma relationship. We found no significant mediation overall, but mediation may be gender-specific. Gender-stratified models displayed countervailing mediation effects among girls for asthma diagnosis by smoking (p = 0.05) and adult-reported housing quality (p = 0.06), which reduced total effects by 35% and 42% respectively. MTO treatment worsened boys' mental health and mental health reduced treatment effects on asthma diagnosis by 27%. Future research should explore other potential mediators and gender-specific mediators of MTO effects on asthma. Improving measurement of housing conditions and other potential mediators may help elucidate the "black box" of neighborhood effects.
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