Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography

Komatsu, Hiroshi; Onoguchi, Goh; Silverstein, Steven M.; Jerotic, Stefan; Sakuma, Atsushi; Kanahara, Nobuhisa; Kakuto, Yoshihisa; Ono, Takashi; Yabana, Takeshi; Nakazawa, Toru; Tomita, Hiroaki

doi:10.1038/s41380-023-02340-4

Cited by 3 publications

(3 citation statements)

References 204 publications

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“…To the best of our knowledge, this is the first study to explore the association between genetic risk for schizophrenia and retinal variations within a large population-based sample using the latest GWAS. 11 Moreover, our results extend prior findings of retinal thinning in patients with schizophrenia compared to healthy individuals, 4,5,8,9,37 demonstrating an association between genetic risk for schizophrenia and these retinal phenotypes.…”

Section: Discussionsupporting

confidence: 80%

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Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

Rabe,

Smigielski,

Georgiadis

et al. 2024

Preprint

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The human retina is part of the central nervous system and can be easily and non- invasively imaged through optical coherence tomography. Imaging the retina may provide insights on central nervous system related disorders such as schizophrenia. Here, our objective was to investigate if variations in retinal phenotypes could be at- tributed to common genetic variations conveying a risk of schizophrenia as measured by polygenic risk scores. We used population data from the UK Biobank, including White British and Irish individuals without diagnosed schizoprenia, and estimated a polygenic risk score for schizophrenia based on the newest genome-wide association study (PGC release 2022). We hypothesized that greater genetic susceptibility to schizophrenia is associated with retinal thinning, especially within the macula. To gain additional mechanistic insights, we conducted pathway-specific polygenic risk score associations analyses, focusing on gene pathways that are related to schizophrenia. Of 65484 individuals recruited, 48208 participants with available matching imaging- genetic data were included in the analysis of whom 22427 (53.48%) were female and 25781 (46.52%) were male. 5148 individuals were excluded on the basis of incomplete optical coherence tomog- raphy data (for all phenotypes), 198 individuals based on the use of antipsychotics and 197 individuals with schizophrenia, schizotypal- and delusional disorders. Our robust principal component regression results showed that polygenic risk scores for schizophrenia were associated with retinal thinning while controlling for confounding factors (b = -0.03, p = 0.007). Similarly, we found that polygenic risk for schizophrenia specific to neuroinflammation gene sets revealed significant associations with retinal thinning (b = -0.03, self-contained p = 0.041 (reflecting the level of association), com- petitive p = 0.05 (reflecting the level of enrichment)). These results go beyond previ- ous studies suggesting a relationship between manifested schizophrenia and retinal phenotypes. They indicate that the retina is a mirror reflecting the genetic complex- ities of schizophrenia. These associations also suggest the potential involvement of the neuroinflammatory pathway, with indications of genetic overlap in certain retinal phenotypes. The findings further indicate that this gene pathway in individuals with a high polygenic risk for schizophrenia could contribute through acute-phase proteins to structural changes in the retina.

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Section: Discussionsupporting

confidence: 80%

“…29 In the current study, we focused on the macula as it contains mutiple layers that based on prior investigations show thinning in individuals diagnosed with schizophrenia. 9,30,31…”

Section: Methodsmentioning

confidence: 99%

Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

Rabe,

Smigielski,

Georgiadis

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…7 Another systematic review looked at studies which have reported retinal abnormalities using optical coherence tomography and electroretinography among schizophrenia spectrum patients. 8 This review reported that the retinal changes in these patients can be both trait and state markers. Eye-tracking studies offer an opportunity to understand oculomotor functioning which correlates with various aspects of brain functioning.…”

Section: Introductionmentioning

confidence: 99%

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I

Ritish,

Reddy,

Sreeraj

et al. 2024

Can J Psychiatry

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Background Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. Aim of the study This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. Methods NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM ( n = 31), HR ( n = 31), and HC ( n = 30) subjects, matched for age (years) ( p = 0.44) and sex ( p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. Results Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). Conclusions AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD.

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Multimorbidity in Severe Mental Illness as Part of the Neurodevelopmental Continuum: Physical Health-Related Endophenotypes of Schizophrenia—A Narrative Review

Genkel,

Domozhirova,

Malinina

2024

Brain Sciences

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Background. The majority of deaths in patients with schizophrenia and other severe mental illnesses (SMIs) are caused by natural causes, such as cardiovascular diseases (CVDs). The increased risk of CVD and other somatic diseases in SMIs cannot be fully explained by the contribution of traditional risk factors, behavioral risk factors, patients’ lifestyle peculiarities, and the influence of antipsychotics. The present review has the following main objectives: (1) to aggregate evidence that neurodevelopmental disorders are the basis of SMIs; (2) to provide a review of studies that have addressed the shared genetic architecture of SMI and cardiovascular disease; and (3) to propose and substantiate the consideration of somatic diseases as independent endophenotypes of SMIs, which will make it possible to place the research of somatic diseases in SMIs within the framework of the concepts of the “neurodevelopmental continuum and gradient” and “endophenotype”. Methods. A comprehensive literature search was performed on 1 July 2024. The search was performed using PubMed and Google Scholar databases up to June 2024. Results. The current literature reveals considerable overlap between the genetic susceptibility loci for SMIs and CVDs. We propose that somatic diseases observed in SMIs that have a shared genetic architecture with SMIs can be considered distinct physical health-related endophenotypes. Conclusions. In this narrative review, the results of recent studies of CVDs in SMIs are summarized. Reframing schizophrenia as a multisystem disease should contribute to the activation of new research on somatic diseases in SMIs.

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Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography

Cited by 3 publications

References 204 publications

Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I

Multimorbidity in Severe Mental Illness as Part of the Neurodevelopmental Continuum: Physical Health-Related Endophenotypes of Schizophrenia—A Narrative Review

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