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ADHD is more closely linked to neurodevelopmental than externalizing and internalizing disorders: A genetically informed multivariate Swedish population study

By Ebba Du Rietz, Erik Pettersson, Isabell Brikell, Laura Ghirardi, Qi Chen, Catharina Hartman, Paul Lichtenstein, Henrik Larsson, Ralf Kuja-Halkola

Posted 27 Feb 2020
medRxiv DOI: 10.1101/2020.02.26.20028175

BackgroundWhile ADHD is currently classified as a neurodevelopmental disorder in the latest diagnostic manuals, the disorder shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalizing and internalizing disorders. This study aimed to investigate if ADHD is etiologically more closely related to neurodevelopmental than externalizing or internalizing disorder clusters after accounting for a general psychopathology factor. MethodsFull- and maternal half-sibling pairs (N=774,416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD-diagnoses were obtained using the Swedish National Patient Register. A higher-order confirmatory factor analytic model was performed to examine associations between ADHD and a general psychopathology factor as well as a neurodevelopmental, externalizing, and internalizing subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD. ResultsADHD was significantly and strongly associated with all three neurodevelopmental, externalizing and internalizing factors (r=0.67-0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r=0.43, 95%Confidence Interval [CI]=0.42-0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalizing-specific factor was smaller (r=0.25, 95%CI=0.24-0.27), and largely influenced by non-shared environmental effects. There remained no internalizing-specific factor after accounting for a general factor. ConclusionsADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences.

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