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Highlights • Longitudinal effect of individual variability at pubertal progression on depressive trajectory was examined. • Accelerated breast development with heightened stress reactivity associates with increased risk of depressive symptoms. • HPA axis reactivity plays a key role in the association between accelerated pubertal progression and depressive symptoms. Abstract Pubertal timing has been suggested as biological factors implicated in the onset of depression in girls. This study aims to examine the prospective association between accelerated pubertal progression with depressive symptoms, and to further explore the possible role of individual reactivity to social stress in this association. A total of 56 girls with early puberty timing (assessed through breast Tanner stage) and 56 age-matched normal breast development girls were recruited at Wave 1 (grade 3) and followed for 4 years biennially. Hypothalamic-pituitary-adrenal axis stress reactivity was indexed by four cortisol samples collected before, during and after the Groningen Social Stress Test (GSST) at Wave 1. Depressive symptoms were interviewed through Mood & Feeling Questionnaire (MFQ) at each wave. About 42.9% (24/56) from early pubertal timing group and 19.6% (11/56) from normal control group were found accelerated breast development during 4-year follow-up. Mixed effects linear models illustrated that among accelerated breast development girls, those with heightened stress reactivity is likely to have a 6.62 (95% CI, 1.14–12.11)-point higher MFQ scores, and 41.9% (95% CI : 25.2 to 58.6%) higher probability for depressive symptoms, compared with girls with persistent normal breast development and moderate stress reactivity. However, no similar effects were found in girls with accelerated breast development but attenuated stress reactivity. The finding suggests that heightened cortisol reactivity to social stress may represent a useful biomarker in identifying girls at greatest risk of development of depressive symptoms following accelerated pubertal progression. [ABSTRACT FROM AUTHOR]