Background: Autonomic nervous system (ANS) measures, including the pupillary light reflex (PLR), are altered in Major Depressive Disorder (MDD).However, effects of age, biological sex, and depression severity on these measures has not been systematically characterized.The effects of repetitive Transcranial Magnetic Stimulation (rTMS) on PLR measures also remains unclear, though prior work linking specific PLR measures to treatment response. Methods:In 101 individuals receiving rTMS for MDD, PLR measures and the Inventory of Depressive Symptomatology (IDS) scores were collected at baseline and every five sessions.Linear mixed-effect models were generated to characterize the influence of age, sex, baseline depression burden, and single and repeated rTMS sessions on PLR.Results: Initial pupil diameter (D0), maximally-constricted diameter (D1), dilation time (T75), dilation velocity (DV), and constriction amplitude (CA) varied with age, sex, and depressive burden, indicating demographic and baseline influences on autonomic tone.IDS scores significantly improved during rTMS treatment (mean 36.31%,p<0.001).After the first session, J o u r n a l P r e -p r o o f D0, D1, T75, and nMCV showed significant pre-to-post changes.Repeated rTMS was associated with modest changes in D0, D1, DV, and latency, while CA and nMCV were unchanged.Baseline-related PLR differences were unaffected by single or repeated sessions.Signal-to-noise ratios showed greater noise than signal.Conclusions: PLR metrics vary with depressive burden, age, and sex, and show acute and cumulative changes across rTMS treatment.These analyses build on our prior work showing PLR metrics are a potential marker of rTMS response.Refinement of these descriptive models may support treatment optimization and outcome prediction.
Leuchter et al. (Sun,) studied this question.