A pair of recently published studies from researchers at UCLA Health suggest that measuring changes in how pupils react to light could help predict recovery from depression and personalise transcranial magnetic stimulation (TMS) treatment of major depressive disorder.
TMS is a safe, non-invasive therapy that uses magnetic fields to stimulate parts of the brain involved in mood regulation. While TMS is proven effective, not all patients respond equally well to the therapy. The ability to predict who will benefit most could allow doctors to better customise and target treatments.
In two recent studies, UCLA scientists found that the pupil’s response to light before treatment correlated with improvements in depression symptoms over the course of therapy. Pupil size reflects activation of the autonomic nervous system, which controls involuntary functions and is negatively impacted in people with depression.
The first study, appearing in the Journal of Affective Disorders, reports on outcomes for 51 patients who underwent daily TMS sessions. Before receiving treatment, researchers measured the patients’ baseline pupillary constriction amplitude, or CA: how much the pupil shrinks when exposed to light. The pupil’s constriction is an indicator of parasympathetic nervous system function. The researchers found a significant association between baseline pupil constriction amplitude and symptom improvement, indicating that a greater constriction amplitude at baseline was associated with a better outcome. In other words, those with larger pupil constriction in response to light at baseline showed greater symptom improvement over their full treatment.
The second study, published in Brain Stimulation, went further and compared patients who were treated for depression with one of two common TMS protocols: 10Hz stimulation and intermittent theta burst stimulation (iTBS). In 10Hz stimulation, magnetic pulses are delivered in a continuous and relatively high-frequency stimulation. iTBS is a faster form of stimulation with bursts of three pulses at 50Hz, repeated with short breaks between bursts. This pattern is thought to mimic the natural rhythm of certain brain activities.
The researchers found that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10Hz treatment.
“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,” said researcher Cole Citrenbaum, lead author of both studies.
Tailored TMS treatments
The researchers propose that measuring pupillary reactivity before starting TMS could guide treatment selection. “Additionally, we may be able to tailor the frequency of stimulation to the individual patient to maximise their benefit from treatment,” Citrenbaum said.
“At the present time, about 65% of patients treated with TMS have a substantial improvement in their depression,” said Dr Andrew F. Leuchter, senior author of both studies. “Our goal is to have more than 85% of patients fully recover from depression. As we better understand the complex brain activity underlying depression, we move closer to matching patients with the treatments that ensure their full recovery. Pupil testing may be one useful tool in reaching this goal.”
The studies add to growing evidence on the benefits of biologically-based personalization in treating major depression. UCLA researchers plan further trials to confirm the value of pupillometry in optimizing transcranial magnetic stimulation.
Source: University of California – Los Angeles Health Sciences
