The neurodevelopmental spectrum: phenotypic architecture, etiology, predictive utility, and specificity across development

Neurodevelopmental conditions are highly heritable, heterogeneous, and frequently co-occur. Transdiagnostic dimensional approaches have advanced understanding and classification of psychiatric disorders, but have largely omitted neurodevelopmental conditions. Using longitudinal data for >10,000 children from the Twins Early Development Study, we investigated the structure of a transdiagnostic “neurodevelopmental spectrum” across development, its etiology, its ability to predict functional outcomes, and the specificity of these associations. Hierarchical exploratory factor modeling of a broad set of traits/symptoms delineated a neurodevelopmental spectrum encompassing neurodevelopmental traits at ages 7, 12, and 16. This spectrum emerged as a distinct dimension alongside separable dimensions of internalizing, externalizing, and psychosis symptoms. The neurodevelopmental spectrum was highly heritable across development in twin analyses (h2=0.60-0.82) and predicted by polygenic scores (PGS) for neurodevelopmental, cognitive, and educational phenotypes (R2 up to 2.30% in single-PGS analyses, 3.36% in multi-PGS analyses). Perinatal and early developmental factors (e.g., low birth weight, language delays) were also associated with this spectrum (R2 up to 8.65%). Individual differences in the neurodevelopmental spectrum predicted cognitive and educational outcomes both concurrently and longitudinally (R2 up to 20.61%), largely due to overlapping genetic effects. Associations with predictors and outcomes remained largely unchanged after adjusting for internalizing, externalizing, and psychosis dimensions, indicating they were specific to the neurodevelopmental spectrum and not attributable to shared variance with other co-occurring symptoms. Our novel results on the phenotypic architecture, etiological validity, predictive utility, and specificity of the neurodevelopmental spectrum across development support its integration into transdiagnostic frameworks, with important implications for advancing research, psychiatric classification, and clinical care.