Neurovascular correlates of retinal microvascular caliber in adolescent bipolar disorder

The connection between vascular and brain metrics is well-studied in older adults, but neglected in youth and in psychiatric populations at increased cardiovascular risk. We therefore examined the association of retinal vascular caliber with cerebral blood flow (CBF) in adolescents with and without bipolar disorder (BD).

Ninety-four adolescents (n = 48 BD, n = 46 controls) completed retinal fundus imaging, yielding estimates of arteriolar and venular diameter. Arterial spin labelling MRI was performed to measure CBF. We tested for associations between retinal vascular caliber and CBF in regions of interest; anterior cingulate cortex (ACC), middle frontal gyrus, and hippocampus in BD and controls separately. Complementary voxel-wise analyses were also performed.

In the BD group, higher arteriovenous ratio (AVR) was associated with greater ACC CBF (β = 0.34, p_uncorrected = 0.02), after controlling for age, sex, and BMI, however this finding did not survive correction for multiple comparisons. The control group did not show any associations (β = 0.13, p_uncorrected = 0.40). Voxel-wise analyses within the BD group detected a significant positive association between AVR and regional CBF in two distinct clusters: i) left hippocampus (p < 0.0001); ii) right middle temporal gyrus (p = 0.04).

Limited sample size; young, medically healthy sample limits signal detection; cross-sectional design.

This study reveals that higher AVR is associated with higher regional CBF in adolescents with BD. Present findings advance understanding of potential neurofunctional mechanisms linking retinal vascular caliber with psychiatric diagnoses. This proof-of-concept study was designed to generate initial insights to guide future studies focusing on the vascular-brain connection in youth and in psychiatry.