Signature of altered retinal microstructures and electrophysiology in schizophrenia spectrum disorders is associated with disease severity and polygenic risk.
electroretinography (ERG)
genetics
magnetic resonance imaging (MRI)
optical coherence tomography (OCT)
retina
schizophrenia
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
26 Apr 2024
26 Apr 2024
Historique:
received:
03
08
2023
revised:
30
03
2024
accepted:
14
04
2024
medline:
29
4
2024
pubmed:
29
4
2024
entrez:
28
4
2024
Statut:
aheadofprint
Résumé
Optical coherence tomography (OCT) and electroretinography (ERG) studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSD). However, it remains unclear which specific retinal layers are affected, how the retina, brain, and clinical symptomatology are connected, and how alterations of the visual system are related to genetic disease risk. OCT, ERG, and brain magnetic resonance imaging (MRI) were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSD and 130 healthy control individuals. The sparse partial least squares (SPLS) algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with the individual polygenetic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual OCT and ERG parameter. The SPLS analysis yielded a phenotype-eye-brain signature of SSD in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSD had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSD that are associated with disease severity and individual polygenetic burden.
Sections du résumé
BACKGROUND
BACKGROUND
Optical coherence tomography (OCT) and electroretinography (ERG) studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSD). However, it remains unclear which specific retinal layers are affected, how the retina, brain, and clinical symptomatology are connected, and how alterations of the visual system are related to genetic disease risk.
METHODS
METHODS
OCT, ERG, and brain magnetic resonance imaging (MRI) were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSD and 130 healthy control individuals. The sparse partial least squares (SPLS) algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with the individual polygenetic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual OCT and ERG parameter.
RESULTS
RESULTS
The SPLS analysis yielded a phenotype-eye-brain signature of SSD in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSD had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude.
CONCLUSIONS
CONCLUSIONS
This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSD that are associated with disease severity and individual polygenetic burden.
Identifiants
pubmed: 38679358
pii: S0006-3223(24)01262-9
doi: 10.1016/j.biopsych.2024.04.014
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Valéria de Almeida
(V)
Stephanie Behrens
(S)
Emanuel Boudriot
(E)
Mattia Campana
(M)
Fanny Dengl
(F)
Peter Falkai
(P)
Laura E Fischer
(LE)
Nadja Gabellini
(N)
Vanessa Gabriel
(V)
Thomas Geyer
(T)
Katharina Hanken
(K)
Alkomiet Hasan
(A)
Genc Hasanaj
(G)
Georgios Ioannou
(G)
Iris Jäger
(I)
Sylvia de Jonge
(S)
Temmuz Karali
(T)
Susanne Karch
(S)
Berkhan Karslı
(B)
Daniel Keeser
(D)
Christoph Kern
(C)
Nicole Klimas
(N)
Lenka Krčmář
(L)
Julian Melcher
(J)
Matin Mortazavi
(M)
Joanna Moussiopoulou
(J)
Karin Neumeier
(K)
Frank Padberg
(F)
Boris Papazov
(B)
Sergi Papiol
(S)
Pauline Pingen
(P)
Oliver Pogarell
(O)
Siegfried Priglinger
(S)
Florian J Raabe
(FJ)
Lukas Roell
(L)
Moritz J Rossner
(MJ)
Andrea Schmitt
(A)
Susanne Schmölz
(S)
Enrico Schulz
(E)
Benedikt Schworm
(B)
Elias Wagner
(E)
Sven Wichert
(S)
Vladislav Yakimov
(V)
Peter Zill
(P)
Florian J Raabe
(FJ)
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.