Eye Movement Abnormalities in Major Depressive Disorder

Junichi Takahashi; Yoji Hirano; Kenichiro Miura; Kentaro Morita; Michiko Fujimoto; Hidenaga Yamamori; Yuka Yasuda; Noriko Kudo; Emiko Shishido; Kosuke Okazaki; Tomoko Shiino; Tomohiro Nakao; Kiyoto Kasai; Ryota Hashimoto; Toshiaki Onitsuka

doi:10.3389/fpsyt.2021.673443

Eye Movement Abnormalities in Major Depressive Disorder

Front Psychiatry. 2021 Aug 10:12:673443. doi: 10.3389/fpsyt.2021.673443. eCollection 2021.

Authors

Junichi Takahashi¹, Yoji Hirano^{1

2}, Kenichiro Miura³, Kentaro Morita^{4

5}, Michiko Fujimoto^{3

6}, Hidenaga Yamamori^{3

6

7}, Yuka Yasuda^{3

8}, Noriko Kudo^{3

9}, Emiko Shishido¹⁰, Kosuke Okazaki¹¹, Tomoko Shiino^{12

13}, Tomohiro Nakao¹, Kiyoto Kasai^{5

14}, Ryota Hashimoto^{3

6}, Toshiaki Onitsuka¹

Affiliations

¹ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
³ Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
⁴ Department of Rehabilitation, The University of Tokyo Hospital, Tokyo, Japan.
⁵ Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁶ Department of Psychiatry, Graduate School of Medicine, Osaka University, Suita, Japan.
⁷ Japan Community Health Care Organization Osaka Hospital, Osaka, Japan.
⁸ Life Grow Brilliant Mental Clinic, Osaka, Japan.
⁹ Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
¹⁰ Division of Cerebral Integration, Department of System Neuroscience, National Institute for Physiological Sciences, Okazaki, Japan.
¹¹ Department of Psychiatry, Nara Medical University, Kashihara, Japan.
¹² Division of Developmental Emotional Intelligence, Research Center for Child Mental Development, University of Fukui, Fukui, Japan.
¹³ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan.
¹⁴ The International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, Tokyo, Japan.

Abstract

Background: Despite their high lifetime prevalence, major depressive disorder (MDD) is often difficult to diagnose, and there is a need for useful biomarkers for the diagnosis of MDD. Eye movements are considered a non-invasive potential biomarker for the diagnosis of psychiatric disorders such as schizophrenia. However, eye movement deficits in MDD remain unclear. Thus, we evaluated detailed eye movement measurements to validate its usefulness as a biomarker in MDD. Methods: Eye movements were recorded from 37 patients with MDD and 400 healthy controls (HCs) using the same system at five University hospitals. We administered free-viewing, fixation stability, and smooth pursuit tests, and obtained 35 eye movement measurements. We performed analyses of covariance with group as an independent variable and age as a covariate. In 4 out of 35 measurements with significant group-by-age interactions, we evaluated aging effects. Discriminant analysis and receiver operating characteristic (ROC) analysis were conducted. Results: In the free-viewing test, scanpath length was significantly shorter in MDD (p = 4.2 × 10^-3). In the smooth pursuit test, duration of saccades was significantly shorter and peak saccade velocity was significantly lower in MDD (p = 3.7 × 10^-3, p = 3.9 × 10^-3, respectively). In the fixation stability test, there were no significant group differences. There were significant group differences in the older cohort, but not in the younger cohort, for the number of fixations, duration of fixation, number of saccades, and fixation density in the free-viewing test. A discriminant analysis using scanpath length in the free-viewing test and peak saccade velocity in the smooth pursuit showed MDD could be distinguished from HCs with 72.1% accuracy. In the ROC analysis, the area under the curve was 0.76 (standard error = 0.05, p = 1.2 × 10^-7, 95% confidence interval = 0.67-0.85). Conclusion: These results suggest that detailed eye movement tests can assist in differentiating MDD from HCs, especially in older subjects.

Keywords: alerted aging effect; discriminant analysis; eye movements; fixation stability test and smooth pursuit test; free-viewing test; major depressive disorder.