Using endocrine profiles to explore subgroups among transdiagnostic neurodiverse children and adolescents

There is considerable heterogeneity in neurodevelopmental disorders (NDDs) that complicates research and clinical support. Although the biological mechanisms of NDDs remain uncertain, emerging studies suggest potential roles of hormone pathways as gonadal, thyroid, glucocorticoid and growth hormones all contribute to brain development. Alterations to these pathways and imbalances of hormones may modulate neural and behavioural development and contribute to the biology of NDDs. Importantly, the field lacks transdiagnostic investigations of endocrine-related phenotypic characteristics. The present study takes a data-driven, transdiagnostic approach to identify and characterize NDD subgroups with distinct endocrine profiles and explores their differences in behavioural phenotypes. We explored the roles of key endocrine analytes spanning specific hormonal systems including the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-gonadal, as well as growth and metabolic axes. Bio-banked serum samples of 186 young people with and without NDDs, aged 3-19 years, were analyzed. Age- and sex-adjusted z-scores were generated for hormone measurements. After dimensionality reduction using robust principal component analysis, k-means clustering generated three diagnosis-agnostic groups with different sex composition, endocrine profiles, and behavioural associations related to externalizing behaviours and adaptive functioning. This exploratory study highlights the potential for endocrine profiles as stratification markers in identifying biologically homogenous subgroups across individuals with and without NDDs.