Association of Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration, With Depressive Symptoms Over Time

Frank Van De Baan ,Indra L M Steens,Coen D A Stehouwer,Miranda T Schram,Carla Kallen ,Abraham A Kroon,Tos T J M Berendschot,Yuri D Foreman,Simone J P M Eussen,Pieter C Dagnelie,Jan S.a.g Schouten ,Carroll A.b Webers ,Marleen M.j Van Greevenbroek ,Thomas T Van Sloten,Anke Wesselius,Annemarie Koster,Nicolaas C Schaper,Anouk F J Geraets ,M.c.j.m Van Dongen ,S.e Köhler ,Ronald M.a Henry

doi:10.1001/jamanetworkopen.2021.34753

Frank Van De Baan , Indra L M Steens + Show 19 more

Open Access

https://doi.org/10.1001/jamanetworkopen.2021.34753

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Abstract

Whether neurodegeneration contributes to the early pathobiology of late-life depression remains incompletely understood. To investigate whether lower retinal nerve fiber layer (RNFL) thickness, a marker of neurodegeneration, is associated with the incidence of clinically relevant depressive symptoms and depressive symptoms over time. This is a population-based cohort study from the Netherlands (The Maastricht Study) with baseline examination between 2010 and 2020 and median (IQR) follow-up of 5.0 (3.0-6.0) years. Participants were recruited from the general population. Individuals with type 2 diabetes were oversampled by design. Data analysis was performed from September 2020 to January 2021. RNFL, an index of neurodegeneration, assessed with optical coherence tomography. Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9 (continuous score, 0-27) at baseline and over time via annual assessments. The presence of clinically relevant depressive symptoms was defined as a PHQ-9 score of 10 or higher. We used data from 4934 participants with depressive symptoms over time (mean [SD] age, 59.7 [8.4] years; 2159 women [50.8%]; 870 had type 2 diabetes [20.5%]). Lower RNFL thickness was associated with higher incidence of clinically relevant depressive symptoms (per 1 SD, hazard ratio 1.11; 95% CI, 1.01-1.23) and more depressive symptoms over time (per 1 SD, rate ratio, 1.04; 95% CI, 1.01-1.06), after adjustment for demographic, cardiovascular, and lifestyle factors. The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time. Hence, neurodegeneration may be associated with the early pathobiology of late-life depression.

Highlights

Late-life depression is a debilitating disease that may be caused by neurodegeneration.[1,2] Clinically, late-life depression is associated with a high comorbidity of psychiatric and physical diseases including neurodegenerative diseases such as Alzheimer disease.[3]
Lower retinal nerve fiber layer (RNFL) thickness was associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time, after adjustment for demographic, cardiovascular, and lifestyle factors
The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time

Summary

Introduction

Late-life depression is a debilitating disease that may be caused by neurodegeneration.[1,2] Clinically, late-life depression is associated with a high comorbidity of psychiatric and physical diseases including neurodegenerative diseases such as Alzheimer disease.[3]. Long-term exposure to stress, microvascular dysfunction, amyloid accumulation, and exposure to adverse risk factors such as hyperglycemia are all thought to contribute to deterioration of cerebral neurodegeneration.[1,4]

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