BACKGROUND: The synergic interaction of risk genes and environmental factors has been thought to play a critical role in mediating emotion-related brain circuitry function and dysfunction in depression and anxiety disorders. Little, however, is known regarding neurodevelopmental bases underlying how maternal negative parenting affects emotion-related brain circuitry linking to adolescent internalizing symptoms and whether this neurobehavioral association is heritable during adolescence. METHODS: The effects of maternal parenting on amygdala-based emotional circuitry and internalizing symptoms were examined by using longitudinal functional magnetic resonance imaging among 100 monozygotic twins and 78 dizygotic twins from early adolescence (age 13 years) to mid-adolescence (age 16 years). The mediation effects among variables of interest and their heritability were assessed by structural equation modeling and quantitative genetic analysis, respectively. RESULTS: Exposure to maternal negative parenting was positively predictive of stronger functional connectivity of the amygdala with the ventrolateral prefrontal cortex. This neural pathway mediated the association between negative parenting and adolescent depressive symptoms and exhibited moderate heritability (21%). CONCLUSIONS: These findings highlight that maternal negative parenting in early adolescence is associated with the development of atypical amygdala-prefrontal connectivity in relation to internalizing depressive symptoms in midadolescence. Such abnormality of emotion-related brain circuitry is heritable to a moderate degree.