Pupillary response to blue light as a biomarker of seasonal pattern in Major Depressive Episode: A clinical study using pupillometry

Depressive disorders are characterized by disturbances in light signal processing. More specifically, an alteration of the melanopsin response is suggested. The post-illumination pupillary response (PIPR) to blue light (post-blue PIPR) is increasingly used as a marker of the activity of intrinsically photosensitive melanopsin ganglion cells (ipRGCs). We hypothesized that individuals with Major Depressive Episode (MDE) who exhibited a higher vulnerability to season patterns showed a decreased ability to transmit light signals to the brain. We explored the correlation between the post-blue PIPR and the Global Seasonality Score (GSS) in 21 patients with MDE. The GSS was assessed using the Seasonal Pattern Assessment Questionnaire (SPAQ). The results revealed that decreased relative and absolute post-blue PIPR, suggesting a melanopsinergic hyposensitivity, were associated independently and significantly with higher seasonality in the psychological factor including a greater seasonal variation in sleep duration, mood, energy level and social activity, but were not associated with higher seasonality in the dietary factor (including weight and appetite seasonal variations) or with the severity of anxiety, depression, or sleep disturbances. Interestingly, mediation analyses highlight independent bidirectional effects of high vulnerability to season of psychological factors and decreased ipRGC sensitivity. Post-blue PIPR could be an objective marker of seasonal changes in daylight exposure in patients with MDE. Further research could explore post-blue PIPR as a state or trait biomarker for depressive disorders and the seasonal pattern, and its potential role in predicting therapeutic response to light therapy.