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

Abstract

Background: While 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. Methods: Full- 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. Results: ADHD 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. Conclusions: ADHD 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.

Insights into attention-deficit/hyperactivity disorder from recent genetic studies

“…Further, emerging evidence from multivariate twin and family studies suggests that ADHD loads strongly onto a general genetic psychopathology factor. After accounting for this general factor, ADHD remains genetically associated with a specific neurodevelopmental factor, while genetic links to externalizing and internalizing psychopathology are considerably attenuated, supporting the neurodevelopmental etiology of ADHD (Du Rietz et al, 2020;Lahey et al, 2011;Pettersson et al, 2013Pettersson et al, , 2015. Although twin and family studies addressing non-psychiatric comorbidity in ADHD are sparse, genetic correlations with somatic/neurological conditions such as asthma, epilepsy and obesity (twin rg=0.20-0.30) are weaker than between ADHD and other psychiatric disorders Chen et al, 2019;Holmberg et al, 2015;Mogensen et al, 2011).…”

Assessing and managing attention-deficit hyperactivity disorder in people with intellectual disability

“…Studies have shown that nearly 70% of people with intellectual disability and ADHD also meet diagnostic criteria for autism spectrum disorder (ASD) (Perera 2021). Recent evidence points in the direction of genetic links between ADHD and the wider group of neurodevelopmental disorders (Rietz 2020). ASD and ADHD share aetiological factors and create greater morbidity and clinical challenges when they co-occur (Leitner 2014).…”