Certain retinal features may be associated with a higher risk of incident depression in a large UK Biobank analysis. Researchers found no independent association between retinal morphologic features and incident anxiety disorders.
In the study, the researchers analyzed data from 36,220 UK Biobank participants aged 40 to 70 years who underwent retinal optical coherence tomography (OCT) imaging and had no diagnosis of depression or anxiety disorders at enrollment. During a median follow-up of 12.5 years, 1,340 of the patients developed depression and 1,373 of them developed anxiety disorders. The researchers evaluated whether baseline retinal layer measurements were associated with subsequent risk of either condition.
In fully adjusted analyses, greater ganglion cell-inner plexiform layer (GCIPL) thickness was associated with an 8% lower likelihood of incident depression, while greater macular thickness was associated with a 9% lower likelihood. Among the retinal measurements examined, GCIPL and macular thickness showed the most consistent associations with depression.
The researchers also observed a dose-response relationship. Compared with the patients in the lowest quartile, those in the highest quartile of GCIPL thickness had a 17% lower risk of depression. Patients in the highest quartile of macular thickness had a 24% lower risk compared with those in the lowest quartile.
The association appeared stronger among female participants. In sex-stratified analyses, each 1–standard deviation increase in GCIPL thickness was associated with a 15% lower likelihood of depression among female participants, while each 1-standard deviation increase in macular thickness was associated with a 16% lower likelihood. The researchers reported statistically significant interactions by sex for both measures.
By contrast, no retinal feature was independently associated with incident anxiety disorders following adjustment for demographic, lifestyle, ocular, and medical factors. Although thicker inner nuclear layer measurements showed an association with anxiety risk in less-adjusted analyses, this finding did not persist in the fully adjusted models. The researchers also identified a potential interaction with body mass index (BMI), with a stronger association observed among participants with lower BMI, but characterized subgroup findings based on sex and BMI as exploratory.
Multiple sensitivity analyses yielded similar results. The findings remained consistent following the exclusion of participants who developed depression or anxiety during the first 4 years of follow-up as well as those with ocular disease, retinal disease, neurologic disorders, or high refractive error. Additional adjustment for physical activity, sleep duration, and mood-affecting medications did not materially change the results.
Several limitations may affect the interpretation of the findings. Because the study was observational, the researchers were unable to establish causality, and reverse causation could not be excluded. Depression and anxiety diagnoses were identified through hospital records, which may have underestimated the true incidence by missing milder cases. The UK Biobank population was predominantly White, which may limit generalizability to other populations.
"Thinner GCIPL and macular thickness were independently associated with increased risk of depression, especially in females," wrote lead study author Yi Li, MMed, of the Department of Ophthalmology and Visual Sciences at The Chinese University of Hong Kong, and colleagues. The researchers added that the findings "highlight a potential role of OCT-detected retinal features as additional biomarkers for at-risk stratification of depression."
The study findings support further investigation of retinal OCT features as potential biomarkers for depression risk stratification, but do not establish whether retinal thinning contributes to the development of depression or reflects underlying processes associated with disease risk.
The study authors reported no competing interests.
Source: BMC Medicine
