Structural and functional alterations in hypothalamic subregions in male patients with alcohol use disorder

Background: The hypothalamus is involved in stress regulation and reward processing, with its various nuclei exhibiting unique functions and connections. However, human neuroimaging studies on the hypothalamic subregions are limited in drug addiction. This study examined the volumes and functional connectivity of hypothalamic subregions in individuals with alcohol use disorder (AUD). Method: The study included 24 male patients with AUD who had maintained abstinence and 24 healthy male controls, all of whom underwent brain structural and resting-state functional magnetic resonance imaging. The hypothalamus was segmented into five subunits using a deep learning-based algorithm, with comparisons of volumes and functional connectivity (FC) between the two groups. The relationships between these measures and alcohol-related characteristics were examined in the AUD group. Results: Findings indicated lower volumes in the anterior-superior (corrected-p < 0.001) and tuberal-superior subunits (corrected-p = 0.002) and altered FC of these and the anterior-inferior subunit among AUD patients (corrected-p < 0.05). Moreover, greater disease severity and a longer history of heavy drinking correlated with lower volumes in the anterior-superior (r = -0.42, p = 0.045) and tuberal-superior subregions (r = -0.61, p = 0.013), respectively. Conversely, a longer abstinence duration was associated with larger volumes in the anterior-superior (r = 0.56, p = 0.008) and tuberal-superior subunits (r = 0.40, p = 0.048) and with higher FC between the tuberal-superior hypothalamus and the thalamus, caudate, and anterior cingulate cortex (r = 0.55, p = 0.014). Conclusions: Our results suggest that specific regional alterations within the hypothalamus, particularly the superior subregions, are associated with AUD, and more importantly, that these alterations may be reversible with prolonged abstinence.