Genetic analysis of retinal cell types reveals synaptic pathology in schizophrenia DOI Open Access
Emanuel Boudriot, Marius Stephan, Finn Rabe

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 12, 2024

Importance: As an accessible part of the central nervous system, retina provides a unique window to study pathophysiological mechanisms brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric neurological disorders. However, it remains largely unclear whether primary disease within contribute observed which specific cell types biological are involved. Objective: To determine affected by genomic risk for explore through converges these types. Design, Setting, Participants: In this study, we combined findings from genome-wide association schizophrenia, bipolar disorder, major depressive multiple sclerosis, Parkinson disease, Alzheimer stroke with single-cell transcriptomic data sets humans, macaques, mice. identify susceptible types, applied MAGMA type enrichment analyses performed subsequent pathway analyses. Furthermore, translated cellular top hit structural level using optical coherence tomography genotyping large population-based UK Biobank cohort (n = 36,349). Main Outcomes Measures: Cell type-specific genetic loading disorder traits gene expression profiles cells. Results: Amacrine cells (interneurons retina) were robustly enriched schizophrenia mammalian species different developmental stages. This was primarily driven genes involved synapse biology. On level, higher polygenic associated thinning ganglion cell-inner plexiform layer, contains dendrites synaptic connections amacrine Moreover, immune populations sclerosis risk. No consistent associations found or stroke. Conclusions Relevance: novel insights into underpinnings highlights as potential proxy pathology schizophrenia.

Language: Английский

Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders DOI
Emanuel Boudriot, Marius Stephan, Finn Rabe

et al.

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: 82(3), P. 285 - 285

Published: Jan. 8, 2025

Importance As an accessible part of the central nervous system, retina provides a unique window to study pathophysiological mechanisms brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric neurological disorders, but it remains largely unclear which specific cell types biological are involved. Objective To determine whether affected by genomic risk for explore through converges these types. Design, Setting, Participants This genetic association combined findings from genome-wide schizophrenia, bipolar disorder, major depressive multiple sclerosis, Parkinson disease, Alzheimer stroke with single-cell transcriptomic datasets humans, macaques, mice. identify susceptible types, Multi-Marker Analysis Genomic Annotation (MAGMA) cell-type enrichment analyses were applied subsequent pathway performed. The cellular top hits translated structural level using optical coherence tomography (acquired between 2009 2010) genotyping data large population-based UK Biobank cohort study. Data analysis was conducted 2022 2024. Main Outcomes Measures Cell type–specific loading disorder traits gene expression profiles cells. Results Expression amacrine cells (interneurons within retina) robustly enriched schizophrenia mammalian species different developmental stages. primarily driven genes involved synapse biology. Moreover, immune populations sclerosis risk. No consistent associations found or stroke. On level, higher polygenic associated thinning ganglion inner plexiform layer, contains dendrites synaptic connections (B, −0.09; 95% CI, −0.16 −0.03; P = .007; n 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher increased thickness nerve fiber layer 0.06; 0.02 0.10; 371; 57.51 843 [54.56%]). Conclusions Relevance novel insights into underpinnings highlights as potential proxy pathology schizophrenia.

Language: Английский

Citations

2
Risk of retinal disease and visual impairment in individuals with psychiatric disorders DOI Creative Commons
Jeffrey Chu, Jacqueline K. Shaia, Hejin Jeong

et al.

Eye, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Abstract Background/Objectives Individuals with a psychiatric disease have been reported to structural variations in the retina, but how this affects retinal risk and vision loss is poorly understood. This study evaluated of visual impairment individuals disorders. Subjects/Methods An exploratory retrospective cohort was conducted through federated health research network that aggregates de-identified EHR data over 95 million across 50 healthcare organizations. ages 50–89 were identified for schizophrenia, bipolar disorder (BD), major depressive (MDD), disease, defined by or blindness using ICD-10 codes. propensity score matched (PSM) on age, sex, race, ethnicity, hypertension, diabetes, dyslipidaemias. Risk ratio calculation statistical analyses network’s analytics tool utilizing 95% confidence intervals. Results After PSM, schizophrenia had 160,414 (average age 65), 391,440 BD (64), 1,962,380 MDD (67). A recorded diagnosis associated decreased likelihood having diagnosis, while diagnoses an increased likelihood. Across all disorders, compared alone. Conclusion Recorded diagnosis. concurrent more likely

Language: Английский

Citations

0
The retina across the psychiatric spectrum: a systematic review and meta-analysis DOI

Nils Kallen,

Giacomo Cecere, Dario Palpella

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract The identification of structural retinal layer differences between patients diagnosed with certain psychiatric disorders and healthy controls has provided a potentially promising route to the biomarkers for these disorders. Optical coherence tomography been used study whether exist in schizophrenia spectrum (SSD), bipolar disorder (BPD), major depressive (MDD), obsessive-compulsive (OCD), attention deficit hyperactivity (ADHD), alcohol opiate use However, there is considerable variation amount available evidence relating each heterogeneity results obtained. We conducted first systematic review meta-analysis across all which data was available. quality graded key confounding variables were accounted for. Of 381 screened articles, 87 included. very low moderate quality. Meta-analyses revealed that compared controls, peripapillary nerve fiber (pRNFL) significantly thinner SSD (SMD = -0.32; p<0.001), BPD -0.4; OCD -0.26; p=0.041), ADHD -0.48; p=0.033). Macular thickness only less -0.59; p<0.001). pRNFL quadrant analyses reduced most prominent superior inferior quadrants. subfield indicated may have region-specific effects on thickness. In conclusion, findings suggest substantial BPD, reinforcing their potential as clinical settings.

Language: Английский

Citations

2
Multimorbidity in Severe Mental Illness as Part of the Neurodevelopmental Continuum: Physical Health-Related Endophenotypes of Schizophrenia—A Narrative Review DOI Creative Commons
V. V. Genkel,

Elena Domozhirova,

Е. В. Малинина

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 725 - 725

Published: July 19, 2024

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

Language: Английский

Citations

0
Genetic analysis of retinal cell types reveals synaptic pathology in schizophrenia DOI Open Access
Emanuel Boudriot, Marius Stephan, Finn Rabe

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 12, 2024

Importance: As an accessible part of the central nervous system, retina provides a unique window to study pathophysiological mechanisms brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric neurological disorders. However, it remains largely unclear whether primary disease within contribute observed which specific cell types biological are involved. Objective: To determine affected by genomic risk for explore through converges these types. Design, Setting, Participants: In this study, we combined findings from genome-wide association schizophrenia, bipolar disorder, major depressive multiple sclerosis, Parkinson disease, Alzheimer stroke with single-cell transcriptomic data sets humans, macaques, mice. identify susceptible types, applied MAGMA type enrichment analyses performed subsequent pathway analyses. Furthermore, translated cellular top hit structural level using optical coherence tomography genotyping large population-based UK Biobank cohort (n = 36,349). Main Outcomes Measures: Cell type-specific genetic loading disorder traits gene expression profiles cells. Results: Amacrine cells (interneurons retina) were robustly enriched schizophrenia mammalian species different developmental stages. This was primarily driven genes involved synapse biology. On level, higher polygenic associated thinning ganglion cell-inner plexiform layer, contains dendrites synaptic connections amacrine Moreover, immune populations sclerosis risk. No consistent associations found or stroke. Conclusions Relevance: novel insights into underpinnings highlights as potential proxy pathology schizophrenia.

Language: Английский

Citations

0