Retinal microvessels reflect familial vulnerability to psychotic symptoms: A comparison of twins discordant for psychotic symptoms and controls

Abstract

Mounting evidence suggests that individuals with schizophrenia have an underlying vulnerability to cardiovascular disease, and a recent study suggested that this vulnerability might be reflected in the retinal microvasculature. The purpose of this study was to test the hypothesis that the retinal microvessels reflect familial vulnerability to psychotic symptoms. Participants were 531 adolescent and young adult twins who took part in the Brisbane Longitudinal Twin Study and the Twins Eye Study in Tasmania. The twins had photographs taken of their retina when they were adolescents or young adults (M age=20.6 years), and retinal vessel diameter was assessed using computer software. The twins completed an assessment of psychosis symptoms approximately six years later. We compared retinal venular diameters of individuals with one or more symptoms of psychosis (n=45), their unaffected co-twins (n=24), and controls (n=462). Individuals with one or more symptoms of psychosis had wider venules (standardized mean=0.29) than controls (standardized mean=-0.04; p=.03), and unaffected co-twins had venular diameters that were intermediate (standardized mean=0.13) between the two groups, suggesting that wide venules may represent a proxy marker of familial vulnerability to psychosis symptoms. Consistent with previous work, there were no differences in arteriolar diameter between individuals with and without symptoms of psychosis. Findings suggest that wide retinal venules may serve as a proxy marker of familial liability to psychosis symptoms. The pathophysiological mechanisms linking psychosis and cardiovascular disease may be operative from early in life, possibly at the level of the microvasculature.

Cerebral ischemia-induced genes are increased in acute schizophrenia: an opportunity for clinical translation of genomic research findings

“…Taken together, nearly all postmortem studies have so far either obtained direct 22,40 or indirect [41][42][43][44] evidence consistent with mild cerebral ischemia in the adult brain of schizophrenic patients. Most importantly, the results presented here are in agreement with established findings from five different fields of schizophrenia research: (1) biochemical, cellular, electroencephalographic, and clinical signs of cerebral hypoxia/ischemia [47][48][49][50] , (2) oxygen insufficiency of the frontal cortex in acute schizophrenic patients detected by near-infrared spectroscopy (NIRS) 51,52 , (3) hypofrontality observed by brain imaging 36 , (4) vascular studies (e.g., 53,54 ), and (5) genetic association studies. 22 For example, Reif et al were able to demonstrate that NOS1, a risk gene for schizophrenia, is involved in reducing brain oxygenation in patients.…”

Evaluation of retinal nerve fiber layer, macular, and choroidal thickness in schizophrenia: spectral optic coherence tomography findings

“…Recently, Meier et al [35] have shown that wider retinal venules were a distinguishing feature of schizophrenia. This finding was also supported by a study on twins that found an association with wider retinal venules and psychosis symptoms [36]. Choroid is the other vascular tissue supplying more than 70% of blood flow in the eye and can also be affected by microvascular changes in schizophrenia.…”

“…The association between microvascular abnormalities and schizophrenia has been an interesting research topic since the 1960s [41]. Demonstration of wider retinal venules in individuals with psychotic symptoms or schizophrenia has drawn attention to the possible role of retinal imaging for clarifying the pathophysiology in these patients [35,36,41]. As a highly vascular tissue supplying oxygen and nutrients to the outer retina, choroid is another candidate for detection of microvascular abnormalities.…”

Retinal vascular abnormalities in schizophrenia and bipolar disorder: A window to the brain

“…2 A related study examined twins discordant for psychotic symptoms with controls, and reported that abnormalities in retinal vessels reflect familial vulnerability to psychotic symptoms. 13 The only study in BD that has examined the retinal microvasculature had adolescent participants, and showed no abnormality. 14 While these studies have provided the first line of evidence for abnormal retinal vessels in SCZ and BD, the findings have not been further replicated.…”