Reduced supraoptic nucleus (SON) volume links to higher autistic and ADHD traits in adults.

The hypothalamus is a critical brain region, orchestrating diverse functions from neuroendocrine regulation to social behavior. Despite its central role in neurodevelopmental disorders like autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), its intricate internal organization has been challenging to study in living humans. Current understanding of these conditions often focuses on synaptic dysfunction, yet neuroendocrine pathways are increasingly recognized as crucial. This study aimed to explore whether specific anterior hypothalamic subunits, particularly those rich in magnocellular neurosecretory nuclei like the paraventricular nucleus (PVN) and supraoptic nucleus (SON), form a structurally coherent axis linked to dimensional traits associated with ASD and ADHD.

Researchers applied a convolutional neural network-based automated segmentation framework to high-resolution T1-weighted MRI data from a non-clinical adult sample (n=23). This allowed for volumetric quantification of ten distinct hypothalamic subunits. The primary endpoints were the associations between these subunit volumes and scores on the Autism-Spectrum Quotient (for autistic traits) and CAARS (for ADHD symptom severity). Statistical analyses included structural covariance, correlation, and bootstrapped path analyses (5,000 iterations), with adjustments for biological sex, age, and total intracranial volume.

Anterior hypothalamic subunits, specifically PVN- and SON-associated volumes, demonstrated a significant positive structural covariance (r=0.51, p=0.022), supporting the hypothesis of a coherent anterior magnocellular-rich network. Crucially, reduced SON-associated volume was significantly associated with higher autistic traits, as measured by the Autism-Spectrum Quotient (r=-0.45, p=0.046). Furthermore, reduced SON-associated volume showed an even stronger association with greater ADHD symptom severity, assessed via CAARS scores (r=-0.59, p=0.006). Bootstrapped path analyses reinforced this network organization, revealing a robust direct association between PVN- and SON-associated volumes (β=0.51, p=0.013).

A significant indirect association was observed between PVN-associated volume and ADHD symptoms via SON-associated volume (β=-0.29, p=0.006), with a marginal indirect association for autistic traits. These findings provide preliminary in vivo evidence linking specific anterior hypothalamic structures to dimensional neurodevelopmental traits.