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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Brain Age Gap Reduction Following Physical Exercise Mirrors Negative Symptom Improvement in Schizophrenia Spectrum Disorders

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Schizophrenia spectrum disorders (SSD) are associated with accelerated brain aging, reflected in an increased age gap. This gap serves as a biomarker, indicating poorer health, cognitive deficits, and greater severity specific symptom domains. Physical exercise holds promise adjunct therapy to mitigate these deficits by potentially promoting recovery. However, the extent of overall improvements health following exercise, along their predictors relationships clusters, yet be determined. study examined metric quantitative indicator recovery response physical exercise. To achieve this, we aggregated data from two randomized controlled trials, analyzing baseline ( n = 134) 3- or 6-month post-exercise 46) individuals SSD. Our findings revealed that patients higher BMI demonstrated recovery, evidenced reduced post-exercise. Furthermore, changes were negative symptoms cognition, suggesting reductions brain-predicted may reflect relief, particularly domains beyond positive symptoms. These results underscore importance support using surrogate marker for tracking clinically relevant highlight need stratified interventions combined lifestyle modifications enhance outcomes Glossary (SSD): Mental conditions characterized psychosis, alteration perception reality. Cardinal include hallucinations (sensory not mirroring reality) delusions (persistent beliefs rooted reality). Positive symptoms: A cluster SSD including complaints distinctively present patiens: hallucinations, delusions, thought disorder (disorganized thinking speech). Negative absent loss interest, motivation, enjoyment, social interactions, flattened affect. Cognitive Another attention, executive function, memory. Biomarker: Objective, quantifiable indicators biological states processes used predict, diagnose, treat illnesses. Brain gap: biomarker aging. Brain-predicted is predicted machine learning algorithm based on imaging data. Subtracting chronological gap, where values indicate aging brain. Neuroplasticity: The brain’s ability reorganize itself through new synaptic connections learning, treatment, injury. Randomized Controlled Trials (RCTs): design randomly assigns participants experimental group control test efficacy intervention.

Language: Английский

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Investigating the association of the plasma lipidomic profile with cognitive performance and genetic risk in the PsyCourse study

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 28, 2025

Abstract Although lipid biology may play a key role in the pathophysiology of mental health disorders such as schizophrenia (SCZ) and bipolar disorder (BD), nature this interplay how it could shape phenotypic presentation, including cognitive performance is still incompletely understood. To address question, we analyzed association plasma level different species with transdiagnostic PsyCourse Study. Plasma lipidomic profiles 623 individuals (188 SCZ, 243 BD, 192 healthy controls) belonging to Study were assessed using liquid chromatography untargeted mass spectrometry. The between 364 annotated from 16 classes six tests was evaluated. Likewise, polygenic risk scores (PRS) for executive function (EF), educational attainment (EA) levels also investigated. In regression analysis, three phosphatidylethanolamine plasmalogen one ceramide class showed significant negative Digit-Symbol test scores. Lipid class-based enrichment analysis LipidR replicated significance phosphatidylethanolamines test, which evaluates processing speed tasks. Polygenic load EF, or EA not associated levels. Our findings suggest link lipids independent disorders. Still, replication warranted better understand if represent an actionable pharmacologic target tackle dysfunction, important unmet clinical need that affects long-term functional outcomes severe

Language: Английский

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The Retinal Age Gap as a Marker of Accelerated Aging in the Early Course of Schizophrenia

Schizophrenia Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Background and Hypothesis Given the available findings confirming accelerated brain aging in schizophrenia (SZ), we conducted a study aimed at verifying whether quantitative retinal morphological data enable age prediction patients present with positive gap (RAG). Study Design Two samples of controls were enrolled: one included 59 SZ 60 controls, all whom underwent optical coherence tomography (OCT) enabling measurement 72 variables. A second sample 65 70 was then combined first sample, to generate database where each subject represented by 28 Four different machine learning (ML) algorithms used for based on z-standardized OCT data. The associations between RAG, demographic, clinical also analyzed. Results Patients from both had significantly higher RAG ranging 5.88 7.44 years depending specific sample. Predictions larger group but fewer variables exhibited relative error. All ML generated similar outcomes regarding age. correlated dose antipsychotic medication severity symptoms. Correlations chronological showed that highest younger patients, about 45 years, it decreased. Conclusions ML-based results corroborated its pharmacological treatment syndrome severity. finding is novel requires replication.

Language: Английский

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Detecting transdiagnostic retinal deviations in mental disorders through normative modeling

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

Published: June 13, 2024

Abstract Objective Several studies have found thinner retinal tissue in mental disorders compared to healthy controls. Because the retina is part of human brain, this suggests that informative brain structure readouts can be obtained efficiently through imaging. Instead focusing on group-level case-control differences, we used normative modeling estimate age-related decline (and its expected variation) and it seen schizophrenia (SZ), bipolar disorder (BD), major depression (MDD). We hypothesized accelerated controls, with SZ being most affected, followed by BD, then MDD. Methods Using UK Biobank data, estimated controls (HC, N = 56,545) for total macular thickness (including coronal subfields) two sublayers (retinal nerve fiber layer; RNFL; ganglion cell-inner plexiform GC-IPL). (N 171), BD 256), MDD 102) HC. Results For HC, pattern thickness, RNFL, GC-IPL was curve-like rather than linear more pronounced males females. disorders, decline-pattern generally faster, driven disorder-specific subfields. There also an enrichment individuals extremely low (infranormal) values. These results were confirmed robustness checks ruled out unspecific confounders. Conclusion findings suggest particularly SZ, involve neurodegenerative detected retina.

Language: Английский

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Contrasting genetic burden for bipolar disorder: Early onset versus late onset in an older adult bipolar disorder sample

European Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 92, P. 29 - 37

Published: Dec. 22, 2024

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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Investigation of choroid plexus variability in schizophrenia-spectrum disorders—insights from a multimodal study

Schizophrenia, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 20, 2024

Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated peripheral inflammation. However, it unclear whether such an delineates a biologically defined subgroup of SSD. Moreover, remains elusive how ChP linked to brain regions inflammation A cross-sectional cohort 132 SSD 107 age-matched healthy controls (HC) underwent cerebral magnetic resonance imaging (MRI) clinical phenotyping investigate the regions. case-control comparison volumes was conducted, structural variance analyzed by employing variability ratio (VR). K-means clustering analysis used identify subgroups distinct patterns ventricular system, clusters were compared terms demographic, clinical, immunological measures. The relationship between regions, previously inflammation, investigated. We did not find significant HC but detected increased VR lateral ventricle volumes. Based on these we identified 3 differences cognitive measures possibly inflammatory markers. Larger volume higher hippocampus, putamen, thalamus HC. This study suggests variability, mean volume, SSD,

Language: Английский

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Multimodal Retinal Imaging Findings in Schizophrenia Spectrum Disorders

Biological Psychiatry, Journal Year: 2024, Volume and Issue: 96(10), P. 769 - 771

Published: Oct. 14, 2024

Language: Английский

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Retinal Optical Coherence Tomography in Bipolar Disorder – A Scoping Review

Neuropsychobiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 23

Published: Dec. 24, 2024

Background: Bipolar disorder (BD) is a psychiatric condition with significant health implications due to its comorbidities, premature mortality, and functional impairments. Despite extensive research on treatment rehabilitation, gaps remain in diagnosis monitoring. Therefore, there need for biomarkers identify individuals at risk disease progression or excacerbation. Developmentally part of the central nervous system, retina represents possible marker observing BD-related structural alterations brain. Summary: The retina's structure can be assessed through optical coherence tomography (OCT), non-invasive cost-effective method. Retinal alterations, particularly retinal nerve fiber layer (RNFL) ganglion cell (GCL), have been associated neurodegenerative disorders cross-sectional OCT studies. This scoping review discusses findings changes BD as well their association characteristics like symptom severity illness duration, highlights potential diagnostic tool treatment. Key Findings: majority studies indicate RNFL GCL thinning patients, which was found correlate clinical some Although data currently limited, possibility that could facilitate monitoring BD, but more needs conducted observe relationship between these parameters BD. Moreover, other factors (e.g., treatment, metabolic inflammatory conditions) may impact changes, longitudinal clarify relationships. Further should focus replicating current findings, understanding role inflammation, differentiating regions affected by

Language: Английский

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