Recent research from UCLA Health indicates that assessing changes in pupil reactions to light may offer insights into predicting recovery from depression and tailoring transcranial magnetic stimulation (TMS) treatment for major depressive disorder.

TMS is a safe, non-invasive therapy utilizing magnetic fields to stimulate brain regions involved in mood regulation. While TMS has proven effectiveness, not all patients respond equally. Predicting who will benefit most could enable doctors to better customize treatments.

In two recent studies, UCLA scientists discovered a correlation between the pupil’s light response before treatment and improvements in depression symptoms during therapy. Pupil size reflects the activity of the autonomic nervous system, which is affected negatively in individuals with depression.

The first study, published in the Journal of Affective Disorders, analyzed outcomes for 51 patients undergoing daily TMS sessions. Prior to treatment, researchers measured baseline pupillary constriction amplitude (CA) — how much the pupil contracts when exposed to light. The constriction is an indicator of parasympathetic nervous system function. The study found a significant connection between baseline pupil constriction amplitude and symptom improvement, suggesting that a greater constriction at baseline was linked to better outcomes.

The second study, published in Brain Stimulation, compared patients receiving depression treatment through two common TMS protocols: 10 Hz stimulation and intermittent theta burst stimulation (iTBS). The researchers found that individuals with slower pupillary constriction experienced significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10 Hz treatment.

Lead researcher Cole Citrenbaum emphasized, “These results suggest we may be able to use a simple test of the pupil to identify who is most likely to respond to electromagnetic stimulation of the brain to treat their depression.” He also noted that measuring pupillary reactivity before starting TMS could help guide personalized treatment selection, potentially leading to improved outcomes for patients.

Dr. Andrew F. Leuchter, senior author of both studies, expressed the goal of achieving more than 85% of patients fully recovering from depression through better understanding of the complex brain activity underlying the condition. Pupil testing could be a valuable tool in reaching this goal.

These studies contribute to the growing body of evidence supporting biologically-based personalization in major depression treatment. UCLA researchers plan further trials to confirm the value of pupillometry in optimizing transcranial magnetic stimulation.