Microvascular abnormality in schizophrenia as shown by retinal imaging

Abstract

Objective: Retinal and cerebral microvessels are structurally and functionally homologous, but unlike cerebral microvessels, retinal microvessels can be noninvasively measured in vivo by retinal imaging. The authors tested the hypothesis that individuals with schizophrenia exhibit microvascular abnormality and evaluated the utility of retinal imaging as a tool for schizophrenia research.

Method: Participants were members of the Dunedin Study, a population-representative cohort followed from birth with 95% retention. Study members underwent retinal imaging at age 38. The authors assessed retinal arteriolar and venular caliber for all members of the cohort, including individuals who developed schizophrenia.

Results: Study members who developed schizophrenia were distinguished by wider retinal venules, suggesting microvascular abnormality reflective of insufficient brain oxygen supply. Analyses that controlled for confounding health conditions suggested that wider retinal venules are not simply an artifact of co-occurring health problems in schizophrenia patients. Wider venules were also associated with a dimensional measure of adult psychosis symptoms and with psychosis symptoms reported in childhood.

Conclusions: The findings provide initial support for the hypothesis that individuals with schizophrenia show microvascular abnormality. Moreover, the results suggest that the same vascular mechanisms underlie subthreshold symptoms and clinical disorder and that these associations may begin early in life. These findings highlight the promise of retinal imaging as a tool for understanding the pathogenesis of schizophrenia.

Figure 1

Retinal digital photograph. Measurements were made for the 6 largest arterioles (red) and venules (blue) passing through the region located 0.50–2.00 disk diameters from the optic disk margin.

Figure 2

Distribution of retinal venular caliber for the healthy, hypertension, pre-diabetes/diabetes, persistent tobacco dependence, persistent depression, and schizophrenia groups. Scores were adjusted for arteriolar caliber and sex and standardized (M=0.00, SD=1.00) on the population-representative cohort. The vertical line represents the mean for the healthy group. Both parametric and nonparametric statistical analyses showed that individuals diagnosed with schizophrenia had significantly wider venules – a finding that does not depend on extreme values.

Figure 3

Mean retinal venular caliber at age 38 as a function of childhood psychosis symptoms. Venular caliber values were adjusted for arteriolar caliber and sex and standardized on the population-representative cohort. As previously described,¹³ no symptoms reflects a summed score of ‘0’ [n=673; 50.2% were male]; weak symptoms reflect a score of ‘1’ [n=103; 66.0% male]; strong symptoms reflect a score of ‘2’ [n=13; 61.5% male]. At minimum, study members could enter the strong symptom group by obtaining a score of 1 (yes, likely) for 2 symptoms, or by obtaining a score of 2 (yes, definitely) for 1 symptom. Children who exhibited strong psychosis symptoms had the widest venular calibers as adults. Error bars = standard errors.