Retinal photography: A window into the cardiovascular-brain link in adolescent bipolar disorder

Objective: The burden of cardiovascular disease in bipolar disorder (BD) exceeds what can be explained by traditional cardiovascular risk factors (CVRFs), lifestyle, and/or medications. Moreover, neurocognitive deficits are a core feature of BD, and are also related to CVRFs. We examined retinal vascular photography, a proxy for cerebral microvasculature, in relation to CVRFs, peripheral microvascular function, and neurocognition among BD adolescents. Methods: Subjects were 30 adolescents with BD and 32 healthy controls (HC). Retinal photography was conducted using a Topcon TRC 50 DX, Type IA camera, following pupil dilation. Retinal arteriolar and venular caliber was measured, from which the arterio-venular ratio (AVR) was computed. All measures were conducted masked to participant diagnosis. Peripheral arterial tonometry measured endothelial function. Neurocognition was assessed using the Cambridge Neuropsychological Tests Automated Battery. Results: AVR was not significantly different between groups (Cohen's d= 0.18, p = 0.103). Higher diastolic blood pressure (BP) was associated with lower (worse) AVR in BD (r = -0.441, p = 0.015) but not HC (r = -0.192, p = 0.293). Similarly, in the BD group only, higher (better) endothelial function was associated with higher AVR (r = 0.375, p = 0.041). Hierarchical regression models confirmed that, independent of covariates, retinal vascular caliber was significantly associated with diastolic BP and endothelial function in BD. Within the BD group, mood scores were significantly negatively correlated with AVR (beta = -0.451, p = 0.044). Limitations: This study's limitations include a small sample size, a cross-sectional study design, and a heterogeneous sample. Conclusion: Retinal photography may offer unique insights regarding the cardiovascular and neurocognitive burden of BD. Larger longitudinal studies are warranted.