Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 18, 2024

Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared loci are not well understood. Our study employs Mendelian randomization (MR) colocalization analyses, alongside multi-omics data, to uncover potential targets for these conditions, thereby informing therapeutic drug development strategies.

Language: Английский

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Treatment of a schizophrenia patient on long-term super-dose antipsychotics: a case report

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Introduction Clozapine and chlorpromazine are widely used for treating schizophrenia. However, irregular medical follow-ups common in patients with schizophrenia, potentially leading to long-term super-dose medication. Managing such cases poses significant challenges clinical psychiatrists. Case presentation This report describes a 24-year-old Han Chinese male diagnosed schizophrenia who had been taking super-doses of clozapine (18–107 tablets/day, 25 mg/tablet) (7–40 50 five months due follow-ups. Upon hospitalization, the doses antipsychotic drugs were gradually tapered, medication regimen was adjusted based on patient’s previous treatment history. Comprehensive health education about also provided. The patient followed four years, during which his psychiatric symptoms remained under partial control. Conclusion Clinicians must consider individual differences efficacy adverse effects antipsychotics weigh benefits risks combination therapy. Future efforts should focus strengthening their families improve compliance outcomes.

Language: Английский

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Current Findings and Potential Mechanisms of KarXT (Xanomeline–Trospium) in Schizophrenia Treatment

Clinical Drug Investigation, Journal Year: 2024, Volume and Issue: 44(7), P. 471 - 493

Published: June 21, 2024

Language: Английский

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Role of Glial Cells and Receptors in Schizophrenia Pathogenesis

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Jan. 27, 2025

Language: Английский

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Causal associations between socioeconomic status and prostate cancer using two-sample Mendelian randomization study

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 7, 2025

Prostate cancer (PCa) is a common form of malignancy among men. The associations between socioeconomic status (SES) indicators and PCa risks remain incompletely elucidated. Through two-sample Mendelian randomization (MR), this research seeks to assess the causal links 4 genetically predicted SES indicators-average total household income before tax, Townsend deprivation index at recruitment, unemployed college or university degree in household-and PCa. Genetic variants were extracted from publicly available genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). We employed inverse variance weighted (IVW), median, mode MR-Egger estimate effect, with sensitivity analyses such Cochran's Q tests, MR-Egger, MR-PRESSO leave-one-out performed detect potential heterogeneity pleiotropy. Our MR analysis revealed unemployment prostate (OR: 3.07, 95%CI:1.12-8.42, P = 0.03). No identified other components cancer. suggested 2 outliers cancer, which rendered significant after removed. pleiotropy are unlikely affect our estimate. results indicated that poses risk factor for incidence findings highlight necessity further exploration into underlying etiology

Language: Английский

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Exposotypes in Psychotic Disorders

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

Published: Feb. 18, 2025

Abstract Psychiatry lags in adopting etiological approaches to diagnosis, prognosis, and outcome prediction compared the rest of medicine. Etiological factors such as childhood trauma (CHT), substance use (SU), socioeconomic status (SES) significantly affect psychotic disorder symptoms. This study applied an agnostic clustering approach identify exposome clusters “Exposotypes (ETs)” examine their relationship with clinical, cognitive, functional outcomes. Using data from individuals disorders (n=1,350), controls (n=623), we assessed between exposotypes Four were identified: ET1 characterized by high CHT SU; ET2, CHT; ET3, ET4, low exposure. Compared demonstrated higher positive general symptoms, anxiety, depression, impulsivity, mania; ET2 had impulsivity; ET3 better cognitive outcomes lower negative Intracranial volume was largest smallest ET2. No group differences schizophrenia polygenic risk scores found. The age onset 5 years earlier than ET4. These findings provide insight into complex interplay trauma, SU, well unique effects on clinical cognition, neurobiology, genetic risk, functioning.

Language: Английский

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Identifying the mediating role of inflammation on the relationship between socioeconomic status and Alzheimer’s disease: a Mendelian randomization analysis and mediation analysis

Journal of Neurology, Journal Year: 2024, Volume and Issue: 271(5), P. 2484 - 2493

Published: Jan. 22, 2024

Language: Английский

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Genetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health

Schizophrenia Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

Abstract Background and Hypothesis Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated SCZ. Study Design We investigated genome-wide datasets related SCZ (52 017 cases 75 889 controls) Psychiatric Genomics Consortium, household income (HI; N = 361 687) UK Biobank, 2202 medical endpoints assessed in up 342 499 FinnGen participants. A phenome-wide genetic correlation analysis HI was performed, also assessing whether correlations were influenced by effect on Additionally, direct effects estimated using multivariable Mendelian randomization (MR). Results showed overlapping 70 traits (P < 2.89 × 10−5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, musculoskeletal phenotypes. these not affected Considering Bonferroni multiple testing correction 7.14 10−4), MR indicated may affect abortion (SCZ OR 1.07; 0.78), panic disorder 1.20; 0.60), personality disorders 1.31; 0.67), use 1.2; 0.68), adjustment 1.18; 0.78). Multivariable confirmed independent HI. Conclusions The liability physical be strongly socioeconomic differences. This suggests SCZ-specific strategies are needed affecting patients high-risk individuals.

Language: Английский

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Causal relationships of gray matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization

Brain Communications, Journal Year: 2024, Volume and Issue: 6(5)

Published: Jan. 1, 2024

Abstract Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple in observational studies, it is unclear whether these associations indicate causal relationships between changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis investigate 202 imaging–derived phenotypes (33 224 individuals) (47 429 cases 68 374 controls) as well (215 1244 controls). Our results suggested that genetically predicted was positively associated with surface area left parahippocampal gyrus (β = 0.018, P 2.383 × 10−4) negatively volumes bilateral caudate (left: β −0.020, 7.203 10−5; right: −0.021, 3.274 10−5) putamen nuclei −0.030, 2.175 10−8; −0.024, 1.047 10−5). In addition, increased risk an paracentral 0.023, 1.025 10−4). Conversely, no evidence found for impact on disease opposite direction. We provide suggestive cortical decreased subcortical volume specific regions. findings shed light disorder.

Language: Английский

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Insights into risk factors of the Metabolic Dysfunction-Associated Steatotic Liver Disease development among patients with schizophrenia

Current Problems of Psychiatry, Journal Year: 2024, Volume and Issue: 25, P. 226 - 238

Published: Nov. 29, 2024

Introduction: The global burden of the Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes a significant clinical problem for healthcare systems worldwide. Apparently, subgroup patients diagnosed with schizophrenia appears to be particularly vulnerable MASLD development. However, exact risk factors in subjects remain unclear date. Material and methods: article is literature narrative review concentrating on particular identification development among schizophrenia. Internet scientific bases were searched by three independent investigators throughout February-July 2024 relevant original articles from 2000-2024 using different combinations MeSH terms: “antipsychotics”, “diabetes”, “dietary habits”, “dyslipidemia”, “inflammation”, “intestinal permeability”, “insulin resistance”, “metabolic-associated fatty liver disease”, “metabolic dysfunction-associated steatotic syndrome”, “non-alcoholic “obesity”, “prevention”, “socioeconomic status”, “treatment”. Furthermore, reference search was conducted find other important manuscripts. Articles language than English excluded search. Scale Assessment Narrative Review used ensure appropriate quality this review. Results: Socioeconomic conditions, improper dietary habits, lack physical activity, smoking addiction issue, gut microbiota dysfunction or use antipsychotics may act as trigger points Conclusions: help establish multidisciplinary programme primarily aimed at its complications prevention, early detection proper treatment.

Language: Английский

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