BACKGROUND: The prevalence of youth anxiety and depression has increased globally, with limited causal explanations. Long-term physical health conditions (LTCs) affect 20-40% of youth, with rates also rising. LTCs are associated with higher rates of youth depression and anxiety
however, it is uncertain whether observed associations are causal or explained by unmeasured confounding or reverse causation. METHODS: Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and Norwegian National Patient Registry, we investigated phenotypic associations between childhood LTCs, and depression and anxiety diagnoses in youth (<
19 years), defined using ICD-10 diagnoses and self-rated measures. We then conducted two-sample Mendelian Randomization (MR) analyses using SNPs associated with childhood LTCs from existing genome-wide association studies (GWAS) as instrumental variables. Outcomes were: (i) diagnoses of major depressive disorder (MDD) and anxiety disorders or elevated symptoms in MoBa, and (ii) youth-onset MDD using summary statistics from a GWAS in iPSYCH2015 cohort. RESULTS: Having any childhood LTC phenotype was associated with elevated youth MDD (OR = 1.48 [95% CIs 1.19, 1.85], p = 4.2×10 CONCLUSIONS: Childhood LTCs are associated with depression and anxiety in youth, however, little evidence of causation between LTCs genetic liability and youth depression/anxiety was identified from MR analyses, except for migraine.