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Pupillometry responses may be a valuable biomarker of depression


A collaborative study has found that pupillometry as a clinical test may help identify biomarkers for major depressive disorder. The test identifies a subgroup of patients with anticipatory hypo-arousal subserving anhedonia symptomatology.

Depressed woman sitting on the floor at the foot of a bed with her head in her hands Image Credit: AdobeStock/Kittiphan

Image Credit: AdobeStock/Kittiphan

A collaborative study between investigators at the Max Planck Institute of Psychiatry, Munich and the Department of Cognitive Sciences, University of California, Irvine found that the usefulness of pupillometry as a clinical test may lie in its ability to identify a specific subgroup of patients with anticipatory hypo-arousal subserving anhedonia symptomatology,1 which may serve as a biomarker of depression, according to the authors.

Led by Andy Brendler, a researcher at the Max Planck Institute of Psychiatry, the group of authors pointed out the current absence of biomarkers for major depressive disorder.

In their study, the investigators analyzed a replication sample of 40 unmedicated patients diagnosed with depression that was not treated and 30 healthy controls. The participants performed a reward anticipation task during which their pupillary responses were measured.

Dr. Brendler and associates explained that there has been recent interest in the pupillary response, some of which includes the following studies.“The pupillary light reflex, which is an index of pupil size in response to light, characterized by an immediate constriction followed by a dilation,2 is altered in depression. It was observed that patients with a MDD diagnosis had an attenuated constriction velocity3 and an overall lower constriction change4-6 of the pupil in response to light stimuli relative to control participants,” the authors reported.

Findings associated with changes in pupillometry responses

The investigators identified a negative correlation between pupillary dilation and symptom load during reward anticipation in patients diagnosed with major depressive disorder. When the data were analyzed from all 136 participants, (ie, 81 unmedicated depressed and 55 healthy control participants) they reported that “reduced pupil dilation in anticipation of reward is inversely associated with anhedonia items of the Beck Depression Inventory in particular.”

In addition, functional magnetic resonance imaging performed simultaneously, showed that the right anterior insula as part of the salience network was negatively correlated with depressive symptom load in general and anhedonia items specifically.

This may provide valuable information for treatment allocation and examining the early treatment response.

The finding of less pupillary response in patients with depression has implications in treatment.

“Considering that an estimated 30% of depressive patients do not improve using the currently available medications, understanding the physiological mechanisms behind depression and fine-tuning diagnosis and treatment accordingly [are] urgently required,” the authors said.

In discussing their findings, the investigators expressed confidence that the anticipatory hypo-arousal identified by pupillometry is correlated with the depressive symptom load in patients with major depressive disorder. They also believe the study provided “evidence that certain depressed patients can be characterized by anticipatory hypo-arousal assessed by decreased pupil dilation during reward anticipation, with specificity for anhedonia and lack of energy-related items.”

This led them to conclude that pupillometry has value as a clinical test to identify a specific subgroup of patients with anticipatory hypo-arousal subserving anhedonia symptomatology. In addition, this may be valuable when considering treatments in individual patients.

  1. Brendler A, Schneider M, Elbau IG, et al. Assessing hypo-arousal during reward anticipation with pupillometry in patients with major depressive disorder: replication and correlations with anhedonia. Sci Rep. 2024;14:344; https://doi.org/10.1038/s41598-023-48792-0
  2. Hall CA, Chilcott RP. Eyeing up the future of the pupillary light reflex in neurodiagnostics. Diagnostics. 2018;8.
  3. Mestanikova A, Ondrejka I, M. Mestanik M, et al. Pupillary light reflex is altered in adolescent depression. Physiol Res. 2017;66:S277–S284.
  4. Laurenzo SA, Kardon R, Ledoltr J, et al. Pupillary response abnormalities in depressive disorders. Psychiat Res. 2016;246:492–499.
  5. Wang J, Fan Y, Zhao, X, Chen N. Pupillometry in Chinese female patients with depression: A pilot study. Int J Environ Res Public Health. 2014;11:2236–2243.
  6. Sekaninova N, Ondrejka I, Bona Olexova L, et al. Oculometric behavior assessed by pupil response is altered in adolescent depression. Physiol Res. 2019;68:S325–S338.
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