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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The collaborative study on the genetics of alcoholism: Genetics

Genes Brain & Behavior, Journal Year: 2023, Volume and Issue: 22(5)

Published: June 30, 2023

Abstract This review describes the genetic approaches and results from family‐based Collaborative Study on Genetics of Alcoholism (COGA). COGA was designed during linkage era to identify genes affecting risk for alcohol use disorder (AUD) related problems, among first AUD‐focused studies subsequently adopt a genome‐wide association (GWAS) approach. COGA's structure, multimodal assessment with gold‐standard clinical neurophysiological data, availability prospective longitudinal phenotyping continues provide insights into etiology AUD disorders. These include investigations trajectories substance disorders, phenome‐wide loci interest, pleiotropy, social genomics, nurture, within‐family comparisons. is one few genetics projects that includes substantial number participants African ancestry. The sharing data biospecimens has been cornerstone project, key contributor large‐scale GWAS consortia. wealth publicly available extensive unique adaptable resource our understanding traits.

Language: Английский

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Whole Genome Sequencing of Pedigrees With High Density of Substance Use and Psychiatric Disorders: A Meeting Report

Genes Brain & Behavior, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 1, 2025

ABSTRACT The National Institute of Drug Abuse convened a panel scientists with expertise in substance use disorders (SUD) and genetic methodologies primarily to determine the feasibility performing whole genome sequencing utilizing existing pedigree collections high density SUD psychiatric disorders. A major focus was on determining if there had been any successes identifying variants for complex traits family‐based designs. Such information could provide assurance that might significant pay‐offs particularly pursuit rare copy number variants. An important goal discuss evaluate optimal strategies studying human samples. Specific topics were (a) consider whether smaller cases typically available family studies versus larger biobanks can reveal unique information; (b) identify potential gaps biobank data be supplemented data; (c) phenotypic definitions (e.g., quantity use, problem‐oriented) collection instruments (self‐report or clinician administered) are both practical efficient collect, likely insights concerning prevention, intervention, medication development. Conclusions reached by included optimism about have occurred ascertained include densely affected pedigrees. Evaluation led, overall, consensus steps should taken utilize conjunction investigations variant discovery.

Language: Английский

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Pleiotropic Effects of Grm7/GRM7 in Shaping Neurodevelopmental Pathways and the Neural Substrate of Complex Behaviors and Disorders

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 392 - 392

Published: March 8, 2025

Natural gene variants of metabotropic glutamate receptor subtype 7 (Grm7), coding for mGluR7, affect individuals’ alcohol-drinking preference. Psychopharmacological investigations have suggested that mGluR7 is also involved in responses to cocaine, morphine, and nicotine exposures. We review the pleiotropic effects Grm7 principle recombinant quantitative trait locus introgression (RQI), which led discovery first mammalian accounting Grm7/GRM7 can play important roles ontogenesis, brain development, predisposition addiction. It other behavioral phenotypes, including emotion, stress, motivated cognition, defensive behavior, pain-related symptoms. This identified pleiotropy modulation neurobehavioral processes by variations Grm7/GRM7. Patterns genes form oligogenic architectures whosecombined additive interaction significantly predispose individuals expressions disorders. Identifying characterizing are necessary understanding complex traits. requires tasks, such as discovering identifying novel genetic elements architecture, unsuitable AI but require classical experimental genetics.

Language: Английский

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A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency

Behavior Genetics, Journal Year: 2023, Volume and Issue: 54(2), P. 151 - 168

Published: Dec. 18, 2023

Language: Английский

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DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8089 - 8089

Published: July 25, 2024

Genetic features of alcohol dependence have been extensively investigated in recent years. A large body studies has underlined the important role genetic variants not only metabolic pathways but also neurobiology dependence, mediated by neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) plays a pivotal serotoninergic transmission; it associated with psychiatric diseases dependence. Transcriptional regulation expression 5-HTT depend on epigenetic modifications, among which DNA methylation (CpG non-CpG) primarily involved, sequence variations occurring intron/exon regions untranslated 5′ 3′, being first sequences for splicing machinery last binding transcription factors micro RNAs. This work intends to shed light known affect or function alcohol-dependent individuals. We found statistically significant difference allelic (p = 0.0083) genotypic 0.0151) frequencies tri-allelic polymorphism, higher alleles genotypes more represented control population. Furthermore, we identified three haplotypes frequent subjects AUD < 0.0001) one population 0.0001). The results obtained polymorphism confirm what already present part literature. requires further be clarified.

Language: Английский

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Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Neurobiology of Stress, Journal Year: 2023, Volume and Issue: 29, P. 100603 - 100603

Published: Dec. 25, 2023

Chronic stress and alcohol (ethanol) use are highly interrelated can change an individual's behavior through molecular adaptations that do not the DNA sequence, but instead gene expression. A recent wealth of research has found these nongenomic changes be transmitted across generations, which could partially account for "missing heritability" observed in genome-wide association studies disorder other stress-related neuropsychiatric disorders. In this review, we summarize behavioral outcomes inheritance chronic ethanol exposure germline mechanisms give rise to heritability. doing so, outline need further to: (1) Investigate individual paternal, maternal, biparental stress- ethanol-related inheritance; (2) Synthesize dissect cross-generational exposure; (3) Determine preconception contribute alcohol-related disease risk, using cancer as example. detailed understanding effects and/or will yield novel insight into impact ancestral perturbations on risk generations uncover actionable targets improve human health.

Language: Английский

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Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

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

Published: Feb. 21, 2024

Abstract Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors AUD pathophysiology. We investigated the interplay between PRS and ethanol human microglia derived from iPSCs individuals with high- or low-PRS (HPRS LPRS) of AUD. Ethanol exposure induced elevated CD68 expression morphological changes differential responses HPRS LPRS microglial cells. Transcriptomic analysis revealed differences MHCII complex phagocytosis-related genes following exposure; cells displayed enhanced phagocytosis increased CLEC7A expression, unlike Synapse numbers co-cultures neurons after alcohol were lower HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into intricate relationship PRS, ethanol, function, potentially influencing neuronal functions developing

Language: Английский

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Another Swim in the Extensive Pool of Zebrafish Research

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 546 - 546

Published: Feb. 29, 2024

The zebrafish has gained utility in modeling biomedical phenomena for discovery research [...]

Language: Английский

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MicroRNAs as Potential Biomarkers of Mental Disorders: Diagnostic and Prognostic Implications

Psikhiatriya, Journal Year: 2024, Volume and Issue: 22(1), P. 68 - 77

Published: March 1, 2024

Background: microRNAs are small non-coding RNAs that play a crucial role in post-transcriptional regulation of gene expression. Recent studies indicate the involvement pathogenesis various psychiatric disorders, which allows to consider them as diagnostic biomarkers and therapeutic targets. The aim this literature review is analyse curren research on formation focusing their potential prognostic biomarkers. Materials methods: find relevant publications, we searched eLibrary PubMed databases using following keywords terms: microRNAs, mental psychological status, biomarkers, diagnosis, prognosis. Conclusion: numerous suggest involved critical molecular pathways associated with including neurotransmission, neurodevelopment, synaptic plasticity. Dysregulation certain has been observed disorders such major depressive disorder, schizophrenia, bipolar anxiety autism spectrum attention-deficit/hyperactivity disorder addictive disorders. It highlighted investigated have high be used opening up possibilities for early detection personalised treatment strategies. identification specific different offers new opportunities develop innovative approaches targeted interventions. However, number challenges remain, differences microRNA expression levels profiles due heterogeneity need standardisation analysis protocols further validation large-scale patient populations. Collaborative efforts between basic genetics researchers clinicians needed harness full diagnosis

Language: Английский

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