Altered hypothalamus functional connectivity and psychological stress in patients with alopecia areata

Alopecia areata (AA) is a nonscarring chronic inflammatory hair loss disease with a complex etiology. Psychological stress and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis have been strongly linked to the etiology of AA, but the associated changes in intrinsic brain activity remain unknown. We hypothesized that patients with AA exhibit altered hypothalamic activity that is linked to psychological stress. This study aimed to characterize the altered hypothalamic activity in patients with AA and its relationship to psychological stress.

A total of 102 patients with AA and 84 age- and sex-matched healthy controls (HCs) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) to assess brain activity and completed neuropsychological evaluations, including the Hamilton Anxiety Rating Scale (HAM-A) score and the Hamilton Depression Rating Scale (HAM-D). Additionally, patients with AA were assessed using the Dermatology Life Quality Index (DLQI), and blood samples were obtained to measure total serum immunoglobulin E (IgE) levels. We chose the hypothalamus as the region of interest (ROI) to compare alterations in hypothalamic of amplitude of low-frequency fluctuation (ALFF) and whole-brain functional connectivity (FC) between patients with AA and HCs. Analyses of the correlation of brain activity and clinical data were conducted, including neuropsychological tests, DLQI, and blood samples.

The HAM-A score, the HAM-D score, and the altered ALFF in the hypothalamus showed a statistically significant difference between patients with AA and HCs (P<0.05). Patients with AA exhibited increased FC between the hypothalamus, the left postcentral gyrus, and right inferior temporal gyrus (Gaussian random field-corrected: voxel <0.001 and cluster <0.05). Moreover, increased FC between the hypothalamus and left postcentral gyrus was positively correlated with HAM-D score (r=0.296; P=0.020), while increased FC between the hypothalamus and the right inferior temporal gyrus was negatively correlated with both DLQI (r=-0.256; P=0.012) and total serum IgE (r=-0.203; P=0.048).

Patients with AA exhibited altered hypothalamus activity and connectivity. These alterations may underlie the neurophysiological basis of psychological stress experienced by patients with AA.