Mapping the cellular etiology of schizophrenia and complex brain phenotypes

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Psychiatric disorders are multifactorial and effective treatments lacking. Probable contributing factors to the challenges in therapeutic development include complexity of human brain high polygenicity psychiatric disorders. Combining well-powered genome-wide brain-wide genetics transcriptomics analyses can deepen our understanding etiology Here, we leverage two landmark resources infer cell types involved schizophrenia, other informative comparison phenotypes. We found both cortical subcortical neuronal associations for bipolar disorder depression. These included somatostatin interneurons, excitatory neurons from retrosplenial cortex eccentric medium spiny-like amygdala. In contrast T B with multiple sclerosis microglial Alzheimer’s disease. provide a framework cell-type-based classification system that lead drug repurposing or opportunities personalized treatments. This work formalizes data-driven, cellular molecular model complex

Language: Английский

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Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with an alcohol use disorder

Complex Psychiatry, Journal Year: 2025, Volume and Issue: 11(1), P. 1 - 11

Published: Feb. 13, 2025

Introduction: Research has identified multiple risk factors associated with suicide attempt (SA) among individuals psychiatric illness. However, there is limited research those an alcohol use disorder (AUD), despite their disproportionately higher rates of SA. Methods: We examined lifetime SA in 4,068 AUD from the Collaborative Study on Genetics Alcoholism (23% SA; 53% female; mean age: 38). explored for across other clinical conditions ascertained a interview, polygenic scores comorbid problems, and neurocognitive functioning. Results: Participants who attempted had greater trauma exposure, major depressive disorder, post-traumatic stress substance disorders (SUDs), suicidal ideation. Polygenic SA, depression, PTSD were increased odds reporting (ORs = 1.22–1.44). reported also decreased right hemispheric frontal-parietal theta interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to did not, but differences small. Conclusions: Overall, report experience levels trauma, have more severe comorbidities, carry problems. Our results demonstrate need further investigate SAs presence SUDs.

Language: Английский

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Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 3, 2020

Abstract Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. observe five significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) TENM2 (rs1862416), extend reported other traits dependence. Using heaviness index from UK Biobank ( N = 33,791), rs2714700 consistently associated; rs1862416 not associated, likely reflecting dependence features captured by index. Both variants influence nearby gene expression (rs2714700/ MAGI2-AS3 hippocampus; rs1862416/ lung), genes spanning dependence-associated enriched cerebellum. (SNP-based heritability 8.6%) genetically correlated with 18 r g 0.40–1.09) co-morbidities. Our results highlight dependence-specific emphasizing FTND as composite phenotype that expands genetic knowledge smoking.

Language: Английский

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Posttraumatic Stress Disorder and Inflammation: Untangling Issues of Bidirectionality

Biological Psychiatry, Journal Year: 2019, Volume and Issue: 87(10), P. 885 - 897

Published: Nov. 14, 2019

Language: Английский

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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 91(1), P. 102 - 117

Published: March 23, 2021

Language: Английский

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