ArticleMolecular psychiatry2024
Association of neurotransmitter pathway polygenic risk with specific symptom profiles in psychosis.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Multi-Trait Genetic Insights Into Schizophrenia Across Ancestries: Genome-Wide Association Meta-Analyses, Machine Learning, and Drug Repurposing Study.Brain and behavior · 2026Pooled it
- Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia.Molecular psychiatry · 2026Article
- Integrating biological pathway polygenic scores and trauma in psychosis: findings from the EU-GEI study.Translational psychiatry · 2026Article
- Brain-targeted epigenetic effects of two emerging psychoplastogens: ketamine & MDMA.Translational psychiatry · 2026Article
- Genetic Pathways Point to the Biology Underlying the Association Between Cannabis Use Disorder and Psychosis.Biological psychiatry global open science · 2026Article
- Shared genetic architecture of psychiatric disorders and ocular diseases: Evidence from genome-wide analyses.IBRO neuroscience reports · 2026Article
- Splitting schizophrenia: divergent cognitive and educational outcomes revealed by genomic structural equation modelling.Molecular psychiatry · 2026Article
- Habenular structural-functional dysconnectivity in bipolar disorder: evidence from multimodal imaging and transcriptomic integration.BMC psychiatry · 2026Article
- Sex differences in AMPA receptor trafficking proteins.Biology of sex differences · 2026Review
- Stage-dependent patterns of cognitive network connectivity in early psychosis.Nature communications · 2025Article
- Glutamate, Contextual Insensitivity, and Disorganized Speech in First-Episode Schizophrenia: A 7T Magnetic Resonance Spectroscopy Study.Biological psychiatry global open science · 2025Article
- Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.Biological psychiatry global open science · 2025Article
- Is There a Natural, Non-addictive, and Non-anti-reward, Safe, Gene-based Solution to Treat Reward Deficiency Syndrome? KB220 Variants vs GLP-1 Analogs.Journal of addiction psychiatry · 2024Article
- Pathway-Specific Polygenic Scores Improve Cross-Ancestry Prediction of Psychosis and Clinical Outcomes.medRxiv : the preprint server for health sciences · 2023Article
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12 authors at 7 institutions in 2 countries.
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Abstract
A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 205 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls. Following genotyping, we calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS summary statistics. To test if overall genetic risk can be partitioned into affected neurotransmitter pathways, we calculated pathway PGSs (pPGSs) for SZ risk affecting each of four major neurotransmitter systems: glutamate, GABA, dopamine, and serotonin. Psychosis subjects had elevated SZ PGS versus controls; cases with SZ or BP diagnoses had stronger SZ or BP risk, respectively. There was no significant association within psychosis cases between individual symptom measures and overall PGS. However, neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes; notably, glutamate was associated with SZ diagnosis and with deficits in cognitive control during task-based fMRI, while dopamine was associated with global functioning. Finally, unbiased endophenotype-driven clustering identified three diagnostically mixed case groups that separated on primary deficits of positive symptoms, negative symptoms, global functioning, and cognitive control. All clusters showed strong genome-wide risk. Cluster 2, characterized by deficits in cognitive control and negative symptoms, additionally showed specific risk concentrated in glutamatergic and GABAergic pathways. Due to the intensive characterization of our subjects, the present study was limited to a relatively small cohort. As such, results should be followed up with additional research at the population and mechanism level. Our study suggests pathway-based PGS analysis may be a powerful path forward to study genetic mechanisms driving psychiatric endophenotypes.
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