Retinal ganglion cell complex thinning in bipolar disorder and first-degree relatives: Evidence from optical...

To evaluate retinal structural differences among patients with bipolar disorder (BD), their unaffected first-degree relatives, and healthy controls using optical coherence tomography (OCT), and to explore whether these changes may serve as endophenotypic markers for BD.

This cross-sectional study included 50 patients with BD, 40 of their unaffected first-degree relatives, and 50 healthy controls. Participants underwent detailed ophthalmologic evaluation, including OCT measurements of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) in both eyes. Group comparisons were conducted using ANOVA or Kruskal-Wallis tests, with ANCOVA to adjust for age and gender. Subgroup analyses were performed based on mood stabilizer use.

GCC thickness in the right eye (superior, inferior, and average) and left eye (superior and average) was significantly reduced in BD patients compared to controls (p < 0.01). Unaffected relatives also demonstrated reduced GCC values in several parameters, supporting a potential heritable component. RNFL thickness was largely comparable across groups, except for increased right inferior RNFL thickness among lithium users. Group differences in GCC remained significant after adjusting for covariates. GCC thinning was more prominent in the right eye, consistent with hypotheses of hemispheric asymmetry in BD.

GCC thinning, observed in both BD patients and their unaffected relatives, may reflect a genetically mediated vulnerability and support its role as an endophenotype of bipolar disorder. Retinal imaging via OCT offers a non-invasive, scalable method for identifying trait-level neurobiological alterations and may aid in early detection of at-risk individuals.