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Pupil response may shed light on who responds to TMS for depression



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, new research suggests.

TMS is a non-invasive therapy that uses magnetic fields to stimulate parts of the brain involved in mood regulation.

While the treatment is proven effective, not all patients respond equally well to the therapy.

The ability to predict which patients will benefit most could allow doctors to better customise and target treatments.

In the 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.

Dr Andrew F. Leuchter, senior author of two new studies and Distinguished Professor of Psychiatry at the Jane and Jerry Semel Institute for Neuroscience and Human Behavior at UCLA, said:

“At the present time, about 65 per cent of patients treated with TMS have a substantial improvement in their depression.

“Our goal is to have more than 85 per cent 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.”

Pupil size reflects the activation of the autonomic nervous system, which controls involuntary functions and is negatively impacted in people with depression.

The first study, reports on outcomes for 51 patients who underwent daily TMS sessions.

Before receiving treatment, researchers measured the participant’ baseline pupillary constriction amplitude, or CA: how much the pupil shrinks when exposed to light.

The pupil’s constriction indicates parasympathetic nervous system function.

The research team 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, the participants with larger pupil constriction in response to light at baseline showed greater symptom improvement over their full treatment.

The second study went further, comparing patients who were treated for depression with one of two common TMS protocols: 10 Hz stimulation and intermittent theta burst stimulation (iTBS).

In 10 Hz stimulation, magnetic pulses are delivered at a fixed rate of 10 pulses per second, or 10 Hz, which is a continuous and relatively high-frequency stimulation.

iTBS is a faster form of stimulation, with bursts of three pulses at 50 Hz, repeated with short breaks between bursts.

The pattern is thought to mimic the natural rhythm of certain brain activities.

The researchers discovered that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10 Hz treatment.

Researcher Cole Citrenbaum, lead author of both studies and a researcher with the TMS Clinical and Research Program at the Semel Institute for Neuroscience and Human Behavior at UCLA, said:

“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.”

The research team proposes that measuring pupillary reactivity before starting TMS could eventually help guide treatment selection on an individual basis.

“Additionally, we may be able to tailor the frequency of stimulation to the individual patient to maximize their benefit from treatment,” Citrenbaum said.

This personalised approach could lead to better outcomes for patients.

The findings 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 optimising transcranial magnetic stimulation.

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