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Background Depression and obesity are common chronic conditions in adolescence, each carrying significant short- and long-term health risks. Their co-occurrence has garnered growing attention due to its strong propensity to persist into adulthood. While previous research separately identified adverse childhood experiences (ACEs), socioeconomic position, and sexual identity as key predictors of MH-OB comorbidity in adolescence, little is known about the longitudinal predictors of comorbidity transitions—whether persistence, remission, or new onset—through late adolescence. This study builds on earlier findings by examining socio-demographic and ACE-related factors associated with these transitions.Methods This longitudinal study analysed data from 10,353 adolescents (49% male at birth, 80.9% non-White) in the MCS. Co-morbidity status was defined using validated measures: obesity/overweight was classified based on International Obesity Task Force (IOTF) criteria, while mental health difficulties (symptoms of depression/anxiety) were assessed using the self-reported SDQ emotional symptoms subscale. Comorbidity status was categorized as no comorbidity, persistent comorbidity, resolved comorbidity newly developed comorbidity. Predictors included sex at birth, ethnicity, sexual identity, parental education, household income quintiles, and cumulative ACEs like parental problem drinking be- haviour, drug use, maternal psychological distress etc. Multinomial logistic regression models including all predictors estimated relative risk ratios (RRR) for associations between predictors and change in comorbidity status between ages 14 and 17.Results At age 14, 7.7% of adolescents were classified as obese, while 19.5% were overweight, 27.8% had poor mental health, and 88% had comorbidity. By age 17, obesity increased to 11.1%, with 19.4% overweight. Comorbidity status changes were: 88.3% no comorbidity, 2.5% persistent co-morbidity, 6.2% new onset comorbidity and 2.8% resolved comorbidity.Lower income, sexual minority identity, sex, and cumulative adverse childhood experiences (ACEs) increased risk for persistent and new onset comorbidity. Adolescents in the lowest income quintile had higher risk for persistent (adjusted RRR=1.55 CI: 0.92–2.60) and new onset comorbidity (aRRR=1.91 CI:1.25–2.92).Sexual minorities, particularly bisexual (aRRR=4.02 CI:2.85–5.67) and gay/lesbian adolescents (aRRR=5.93 CI: 3.62–9.72), had higher risk for persistent comorbidity. Female adolescents were more likely to experience persistent comorbidity (aRRR 4.15 CI: 3.04–5.67). Cumulative ACEs further amplified risks (≥3 ACEs: 1.53 CI: 1.01–2.33, p=0.03). These findings highlight the influence of structural inequities and early-life adversity on adolescent health trajectories.Conclusion Disadvantaged groups across all predictors of interest had higher risk for persistent and newly developed comorbidity, highlighting the cumulative impact of socioeconomic disadvantage, sex at birth disparities, sexual minority identity, and ACEs. While some subgroups also exhibited comorbidity remission, these patterns warrant further exploration. Findings emphasize the need for equitable interventions addressing structural inequities among high-risk subgroups.