Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders

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

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Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Nature Mental Health, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Language: Английский

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Genetic analysis of retinal cell types reveals synaptic pathology in schizophrenia

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

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

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

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