Kenneth S Kendler1,2, Henrik Ohlsson3, Sean Clouston4, Abigail A Fagan5, Jan Sundquist3,6,7, Kristina Sundquist3,6,7. 1. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. 2. Department of Psychiatry, Virginia Commonwealth University, RichmondVA, USA. 3. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 4. Department of Family, Population, and Preventive Medicine, Program in Public Health, Stony Brook University Health Sciences Center, Stony Brook, NY, USA. 5. Department of Sociology, Criminology & Law, University of Florida, Gainesville, FL, USA. 6. Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA. 7. Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Japan.
Abstract
BACKGROUND: We sought to quantify and investigate the causal nature of the association between resilience at age 18 and future drug abuse (DA). METHOD: In a national sample of Swedish men (n = 1 392 800), followed for a mean of 30.3 years, resilience was assessed during military conscription and DA defined from medical, criminal and pharmacy registers. For causal inference, we utilized three methods: (i) instrumental variable analyses with the month of birth as the instrument; (ii) co-relative analyses using the general population, cousins, siblings and monozygotic twins; and (iii) propensity scoring on a subsample (n = 48 548) with strong resilience predictors. Cox proportional hazards models were utilized to examine survival time till DA diagnosis. RESULTS: Low resilience was most robustly predicted from internalizing symptoms. Lower levels of standardized resilience strongly predicted the risk for DA (HR = 2.31, 95% CIs 2.28-2.33). In instrumental, co-relative, and propensity score analyses, the association between resilience and DA was estimated at HR = 3.06 (2.44-3.85), 1.34 (1.28-1.39), and 1.40 (1.28-1.53), respectively. Sensitivity analyses suggested that our instrument was weak and, despite our large sample, likely under-estimated confounding. CONCLUSIONS: Low resilience strongly predicts DA risk. Three different causal analysis methods, with divergent assumptions, concurred in estimating that an appreciable proportion of this association was causal, probably around 40%, with the remainder arising from confounding variables many of which are likely familial. Consistent with prior interventions focused on substance use prevention, our results suggest that prevention programs that increase resilience in adolescence should meaningfully reduce the long-term risk for DA.
BACKGROUND: We sought to quantify and investigate the causal nature of the association between resilience at age 18 and future drug abuse (DA). METHOD: In a national sample of Swedish men (n = 1 392 800), followed for a mean of 30.3 years, resilience was assessed during military conscription and DA defined from medical, criminal and pharmacy registers. For causal inference, we utilized three methods: (i) instrumental variable analyses with the month of birth as the instrument; (ii) co-relative analyses using the general population, cousins, siblings and monozygotic twins; and (iii) propensity scoring on a subsample (n = 48 548) with strong resilience predictors. Cox proportional hazards models were utilized to examine survival time till DA diagnosis. RESULTS: Low resilience was most robustly predicted from internalizing symptoms. Lower levels of standardized resilience strongly predicted the risk for DA (HR = 2.31, 95% CIs 2.28-2.33). In instrumental, co-relative, and propensity score analyses, the association between resilience and DA was estimated at HR = 3.06 (2.44-3.85), 1.34 (1.28-1.39), and 1.40 (1.28-1.53), respectively. Sensitivity analyses suggested that our instrument was weak and, despite our large sample, likely under-estimated confounding. CONCLUSIONS: Low resilience strongly predicts DA risk. Three different causal analysis methods, with divergent assumptions, concurred in estimating that an appreciable proportion of this association was causal, probably around 40%, with the remainder arising from confounding variables many of which are likely familial. Consistent with prior interventions focused on substance use prevention, our results suggest that prevention programs that increase resilience in adolescence should meaningfully reduce the long-term risk for DA.
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