Altered pupil light and darkness reflex and eye-blink responses in late-life depression

Abstract

Background: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.

Methods: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.

Results: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.

Conclusions: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.

Keywords: Autonomic function; Eye blink rate; Pupil light and darkness reflex; Pupillometry.

Fig. 1

A Experimental paradigm. Each trial started with a central fixation point on a gray background. After a delay, the background luminance either increased (20–15 cd/m²), decreased (5–0.1 cd/m²), or stayed the same (10 cd/m²). Participants were required to maintain steady fixation for an additional 2000–2500 ms. B Measurements of pupil response dynamics. PROL: pupil response onset latency. Peak Velocity: peak pupil response velocity. Amplitude: peak pupil response size. Peak Time: time to peak response. Bkgd: background

Fig. 2

Tonic pupil size and blink rate effects for each experimental group. Dynamics of absolute pupil diameter following background luminance change in different conditions (A). Mean pupil sizes (tonic pupil size) at the baseline epoch (-200 to 0 ms) (B), mean coefficient of variation of tonic pupil size (C), and eye blink rate (D) shown for different experimental groups. In A, the shaded colored regions surrounding the pupil response curves represent the ± standard error range (across participants) for different conditions. The gray area represents the epoch selected for tonic pupil size analyses. In B-D, the large-squares and error-bars represent the mean values ± standard error across participants. The small circles represent the mean value for each participant. White: background luminance 20 cd/m². Bright: background luminance 10 cd/m². NoChange: background luminance 10 cd/m² (stayed the same). Dark: background luminance 5 cd/m². Black: background luminance 0.1 cd/m². healthy younger adults. YOUNG: healthy younger adults. OLD: healthy age-matched older adults. LLD: late-life depression patients. Bkgd: background. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001

Fig. 3

Pupil light and darkness reflex responses for each experimental group. Dynamics of baseline-corrected pupil diameter following background luminance change in different conditions (A). Normalized pupil light and darkness responses (light/darkness responses minus no change responses) (B). Mean pupil sizes at the light (600-900ms) or darkness (1900-2000ms) epoch (C), and mean coefficient of variation of PLR and PDR pupil size (D) shown for different conditions and experimental groups. In A-B, the shaded colored regions surrounding the pupil response curves represent the ± standard error range (across participants) for different conditions. In B, the light and darkness epochs for pupil size are shaded in colors. In C-D, the large-squares and error-bars represent the mean values ± standard error across participants. The small circles represent the mean value for each participant. White: background luminance 20 cd/m². Bright: background luminance 10 cd/m². NoChange: background luminance 10 cd/m². Dark: background luminance 5 cd/m². Black: background luminance 0.1 cd/m². healthy younger adults. YOUNG: healthy younger adults. OLD: healthy age-matched older adults. LLD: late-life depression patients. Bkgd: background. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001

Fig. 4

Pupil metrics for each experimental group. Mean PROL (A), max response amplitude (B), max response peak velocity (C), and time to peak response (D) shown for different conditions and experimental groups. In A-D, the large-squares and error-bars represent the mean values ± standard error across participants. The small circles represent the mean value for each participant. White: background luminance 20 cd/m². Bright: background luminance 10 cd/m². Dark: background luminance 5 cd/m². Black: background luminance 0.1 cd/m². healthy younger adults. YOUNG: healthy younger adults. OLD: healthy age-matched older adults. LLD: late-life depression patients. PROL: pupil response onset latency. Peak Velocity: peak pupil response velocity. Max amplitude: peak pupil response size. Peak Time: time to peak response. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001

Fig. 5

Inter-individual correlations between pupil and blink responses and GDS-15 scores. Correlation between GDS-15 scores and tonic pupil size (A), light reflex responses (B), light reflex responses (C), eye blink rate (D). OLD: healthy age-matched older adults. LLD: late-life depression patients. GDS: Geriatric Depression Scale

Fig. 6

Inter-individual correlations between pupil and blink responses and PHQ-15 scores. Correlation between PHQ-15 scores and tonic pupil size (A), light reflex responses (B), light reflex responses (C), eye blink rate (D). OLD: healthy age-matched older adults. LLD: late-life depression patients. PHQ: Patient Health Questionnaire

Fig. 7

Inter-individual correlations between pupil and blink responses and MoCA scores. Correlation between MoCA scores and tonic pupil size (A), light reflex responses (B), light reflex responses (C), eye blink rate (D). OLD: healthy age-matched older adults. LLD: late-life depression patients. MoCA: Montreal Cognitive Assessment