New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

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Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders

JAMA Psychiatry, Journal Year: 2023, Volume and Issue: 80(4), P. 360 - 360

Published: Feb. 8, 2023

Importance Comorbidities and genetic correlations between gastrointestinal tract diseases psychiatric disorders have been widely reported, with the gut-brain axis (GBA) hypothesized as a potential biological basis. However, degree to which shared determinants are involved in these associations underlying GBA is unclear. Objective To investigate etiology identify genomic loci, genes, pathways. Design, Setting, Participants This genome-wide pleiotropic association study using summary statistics from publicly available data sources was performed various statistical approaches sequentially single-nucleotide variation (SNV; formerly polymorphism [SNP]), gene levels pathways disentangle 4 (inflammatory bowel disease, irritable syndrome, peptic ulcer gastroesophageal reflux disease) 6 (schizophrenia, bipolar disorder, major depressive attention-deficit/hyperactivity posttraumatic stress anorexia nervosa). Data were collected March 10, 2021, August 25, analysis January 8 through May 30, 2022. Main Outcomes Measures The primary outcomes consisted of list disorders. Results Extensive overlaps found among 22 24 trait pairs. Pleiotropic under composite null hypothesis identified 2910 significant SNVs 19 pairs, 83 loci colocalized detected. Gene-based 158 unique candidate highly enriched certain GBA-related phenotypes tissues, whereas pathway enrichment further highlighted primarily involving cell adhesion, synaptic structure function, immune differentiation. Several also causal variants gut microbiomes. Mendelian randomization illustrated vertical pleiotropy across pairwise traits. Notably, many for multiple traits, such 1q32.1 ( INAVA ), 19q13.33 FUT2 11q23.2 NCAM1 1p32.3 LRP8 ). Conclusions Relevance These findings suggest that extensively distributed genome. not only support basis but important implications intervention treatment targets simultaneously.

Language: Английский

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Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(3), P. 366 - 387

Published: Sept. 15, 2023

Populations with common physical diseases – such as cardiovascular diseases, cancer and neurodegenerative disorders experience substantially higher rates of major depressive disorder (MDD) than the general population. On other hand, people living MDD have a greater risk for many diseases. This high level comorbidity is associated worse outcomes, reduced adherence to treatment, increased mortality, health care utilization costs. Comorbidity can also result in range clinical challenges, more complicated therapeutic alliance, issues pertaining adaptive behaviors, drug‐drug interactions adverse events induced by medications used mental disorders. Potential explanations prevalence above involve shared genetic biological pathways. These latter include inflammation, gut microbiome, mitochondrial function energy metabolism, hypothalamic‐pituitary‐adrenal axis dysregulation, brain structure function. Furthermore, several antecedents related social factors (e.g., socioeconomic status), lifestyle variables activity, diet, sleep), stressful live childhood trauma). Pharmacotherapies psychotherapies are effective treatments comorbid MDD, introduction interventions well collaborative models digital technologies provide promising strategies improving management. paper aims detailed overview epidemiology specific including bidirectional risk; pathways potentially implicated pathogenesis diseases; socio‐environmental that serve both protective factors; management prevention treatment. We conclude future directions emerging research optimal

Language: Английский

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Evaluation of Brain-Body Health in Individuals With Common Neuropsychiatric Disorders

JAMA Psychiatry, Journal Year: 2023, Volume and Issue: 80(6), P. 567 - 567

Published: April 26, 2023

Physical health and chronic medical comorbidities are underestimated, inadequately treated, often overlooked in psychiatry. A multiorgan, systemwide characterization of brain body neuropsychiatric disorders may enable systematic evaluation brain-body status patients potentially identify new therapeutic targets.

Language: Английский

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Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 1, 2024

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD co-morbid conditions. We investigated the genetic contributions PTSD, 18 diseases, 3 immune/inflammatory biomarkers. Univariate MiXeR was used contrast architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) performed independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted median MR estimates evaluated. Sensitivity analyses uncorrelated (MR PRESSO) correlated horizontal pleiotropy (CAUSE) also performed. considerably more polygenic (10,863 influential variants) than (median 255 variants). However, evidenced correlation with nine three inflammatory had putative effects on thyroid disease (p = 0.00009) C-reactive protein (CRP) 4.3 × 10-7). Inferences not substantially altered by sensitivity analyses. Additionally, PTSD-autoimmune association remained in multivariable analysis adjusted genetically predicted biomarkers as potential mechanistic pathway variables. No a effect (all p values > 0.05). Although models supported associations CRP, adequate explain CRP 0.18). In summary, our results overlap inflammation. has disease, consistent existing epidemiologic evidence. A previously reported is potentially confounded genetics. Together, highlight nuanced links disorders, associated signatures, importance targeting related pathways protect against disability.

Language: Английский

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The Microbiota–Gut–Brain Axis and Neurological Disorders: A Comprehensive Review

Life, Journal Year: 2024, Volume and Issue: 14(10), P. 1234 - 1234

Published: Sept. 26, 2024

Microbes have inhabited the earth for hundreds of millions years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between central nervous system (CNS), enteric (ENS), and emotional cognitive centres brain. field research on gut-brain has grown significantly during past two decades. Signalling occurs gut microbiota brain through neural, endocrine, immune, humoral pathways. A substantial body evidence indicates that MGBA plays pivotal role in various neurological diseases. include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity (ADHD), non-Alzheimer's neurodegeneration dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), temporal epilepsy (TLE), depression, schizophrenia (SCZ). Furthermore, correlation therapeutics will be discussed. Conversely, mood delivery, exercise, psychotropic agents, stress, neurologic drugs can influence MGBA. By understanding MGBA, it may possible to facilitate into microbial-based interventions therapeutic strategies

Language: Английский

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Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis

Psychological Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: April 2, 2024

Background The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared components causality relationship them remains unclear. Methods By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), Crohn's (CD), we conducted a comprehensive pleiotropic analysis uncover loci, genes, or biological processes SCZ each UC, CD, independently. Univariable multivariable Mendelian randomization (MR) analyses were applied assess across these two disorders. Results genetically correlated with IBD ( r g = 0.14, p 3.65 × 10 −9 ), UC 0.15, 4.88 −8 CD 0.12, 2.27 −6 all surpassed Bonferroni correction. Cross-trait meta-analysis identified 64, 52, 66 significantly independent loci associated respectively. Follow-up gene-based found 11 novel genes KAT5 , RABEP1 ELP5 CSNK1G1 etc) joint phenotypes. Co-expression pathway enrichment illustrated those mainly involved core immune-related signal transduction cerebral disorder-related pathways. In univariable MR, predisposition was an increased risk (OR 1.11, 95% CI 1.07–1.15, 1.85 ). Multivariable MR indicated causal effect liability on Actinobacteria 1.06–1.16, 1.34 ) BMI 1.04–1.18, 1.84 −3 Conclusions We confirmed basis, loci/genes, providing insights into mechanism therapeutic targets underlying

Language: Английский

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Biological pathways underlying the relationship between childhood maltreatment and Multimorbidity: A Two-Step, multivariable Mendelian randomisation study

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Polygenic Resilience Scores are Associated With Lower Penetrance of Schizophrenia Risk Genes, Protection Against Psychiatric and Medical Disorders, and Enhanced Mental Well-Being and Cognition

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

Published: Feb. 26, 2025

In the past decade, significant advances have been made in finding genomic risk loci for schizophrenia (SCZ). This, turn, has enabled search SCZ resilience that mitigate impact of genes. We identified first profile SCZ, completely independent from known though it remains unclear whether foster protection against adverse states associated with involving clinical, cognitive, and brain-structural phenotypes. analyzed phenotypic data 459 784 participants UK Biobank, using regression models to estimate interaction effects scores on phenotypes spanning multiple scales. found afforded lifetime psychiatric (schizophrenia, bipolar disorder, anxiety, depression) medical disorders (such as type 2 diabetes, cardiovascular, digestive metabolic disorders). Resilience also moderated loci, self-harm behavior greater fluid intelligence scores. The main are observed absence a moderating effect some instances, such associations larger brain structures. Overall, this study highlights wide range significantly within general population, revealing distinct patterns separate those loci. may protect serious outcomes, comorbidities, cognitive impairment. Therefore, is conceivable facilitate adaptive processes linked improved health life expectancy.

Language: Английский

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Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 119, P. 767 - 780

Published: April 25, 2024

Language: Английский

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