RNA Editing Signatures Powered by Artificial Intelligence: A New Frontier in Differentiating Schizophrenia, Bipolar, and Schizoaffective Disorders DOI Open Access

Francisco Jesus Checa-Robles,

Nicolas Salvetat,

Christopher Cayzac

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12981 - 12981

Published: Dec. 3, 2024

Mental health disorders are devastating illnesses, often misdiagnosed due to overlapping clinical symptoms. Among these conditions, bipolar disorder, schizophrenia, and schizoaffective disorder particularly difficult distinguish, as they share alternating positive negative mood Accurate timely diagnosis of diseases is crucial ensure effective treatment tailor therapeutic management each individual patient. In this context, it essential move beyond standard assessment employ innovative approaches identify new biomarkers that can be reliably quantified. We previously identified a panel RNA editing capable differentiating healthy controls from depressed patients and, among patients, those with major depressive disorder. study, we integrated Adenosine-to-Inosine blood data through machine learning algorithms establish specific signatures for schizophrenia spectrum disorders. This groundbreaking study paves the way application in other psychiatric disorders, such It represents first proof-of-concept provides compelling evidence establishment an signature conditions.

Language: Английский

Neurobehavioral dysfunction in a mouse model of Down syndrome: upregulation of cystathionine β-synthase, H2S overproduction, altered protein persulfidation, synaptic dysfunction, endoplasmic reticulum stress, and autophagy DOI Creative Commons

Theodora Panagaki,

Lucia Janickova,

Dunja Petrovic

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 4275 - 4314

Published: April 1, 2024

Down syndrome (DS) is a genetic condition where the person born with an extra chromosome 21. DS associated accelerated aging; people are prone to age-related neurological conditions including early-onset Alzheimer's disease. Using Dp(17)3Yey/ + mice, which overexpresses portion of mouse 17, encodes for transsulfuration enzyme cystathionine β-synthase (CBS), we investigated functional role CBS/hydrogen sulfide (H

Language: Английский

Citations

8
The effects of childhood adversity on twenty-five disease biomarkers and twenty health conditions in adulthood: Differences by sex and stressor type DOI Creative Commons
Jenna Alley, Jeffrey Gassen, George M. Slavich

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 123, P. 164 - 176

Published: July 25, 2024

Although early adversity is now recognized as a major public health concern, it remains unclear if the effects of early-life stressors on disease biology and differ by sex or stressor type. Because childhood often covary, examining whether such typically occur together (e.g., cumulative adversity) in distinct multivariate patterns needed to determine how different life uniquely affect health. To investigate, we conducted latent class analyses (LCA) identify clusters adults experiencing multiple (N=2,111, Mage = 53.04, 54.8 % female) Midlife United States (MIDUS) Study. We then tested exposure groups, individual stressors, related 25 biomarkers inflammation, metabolism, stress, 20 conditions. Multivariate effect sizes were estimated using Mahalanobis's D. Optimal LCA models yielded three female (Low-, Moderate-, High-Stress) two male (Low- classes. The High-Stress classes had greater inflammation (male: D=0.43; female: D=0.59) poorer metabolic D=0.32–0.33; D=0.32–0.47). They also more cardiovascular HR=1.56 [1.17, 2.07]; HR=1.97 [1.50, 2.58]), cancer HR=2.41 [1.52, 3.84]; HR=2.51 [1.45, 4.35]), HR=1.54 [1.16, 2.03]; HR=2.01 [1.43, 2.83]), thyroid HR=3.65 [1.87, 7.12]; HR=2.25 [1.36, 3.74]), arthritis HR=1.81 [1.30, 2.54]; [1.41, 2.74]), mental/behavioral problems HR=2.62 [1.90, 3.62]; female; HR=3.67 [2.72, 4.94]). Moreover, these outcomes sex- stressor-specific manner. Childhood portends worse biological elevated risk for many These findings advance stress theory may help inform precision interventions managing stress.

Language: Английский

Citations

6
Dynamic Lipidome Reorganization in Response to Heat Shock Stress DOI Creative Commons
Luis E. Solano, Uri Keshet,

Andrew Reinschmidt

et al.

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

Published: Feb. 23, 2025

Abstract The heat shock response (HSR) is a conserved cellular mechanism critical for adaptation to environmental and physiological stressors, with broad implications cell survival, immune responses, cancer biology. While the HSR has been extensively studied at proteomic transcriptomic levels, role of lipid metabolism membrane reorganization remains underexplored. Here, we integrate mass spectrometry-based lipidomics RNA sequencing characterize global lipidomic changes in HeLa cells exposed three conditions: control, (HS), HS eight hours recovery. Heat shock-induced extensive remodeling, including significant increases fatty acids, glycerophospholipids, sphingolipids, partial normalization during Transcriptomic analysis identified over 2,700 upregulated 2,300 downregulated genes under shock, GO enrichment suggesting potential transcriptional contributions metabolism. However, alone did not fully explain observed shifts, additional layers regulation. Joint pathway revealed glycerophospholipid sphingolipid metabolism, while network transport regulators (STAB2, APOB), stress-linked metabolic nodes (KNG1), persistent These findings provide comprehensive framework understanding lipid-mediated mechanisms highlight importance multi-omics integration stress disease

Language: Английский

Citations

0
Rethinking Depression—Beyond Neurotransmitters: An Integrated Psychoneuroendocrineimmunology Framework for Depression’s Pathophysiology and Tailored Treatment DOI Open Access
Anna Giulia Bottaccioli, Mauro Bologna, Francesco Bottaccioli

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2759 - 2759

Published: March 19, 2025

It is known that the effectiveness of drug treatment for depression, ammine deficit based, largely unsatisfactory. In this review, we examine proposal a precision therapy has emerged and received strong push by identification role inflammation in depression. However, psychiatry risks being caught reductionist trap searching molecular switch resets whole system switches off disease. This an illusion since human complex depression systemic variable disorder. study, show inadequacy paradigm, and, at same time, illustrate superiority paradigm centered on psychoneuroendocrineimmunology (PNEI). According to PNEI disease being, caused different sources working together: psychological, biological, behavioral. means knowing biological psychological history subject, identifying relational crisis factors, building personalized treatments targeting those factors with tools medicine psychology, which are not reducible combination drugs psychotherapy. Our presents shift both theoretical practical, enables clinicians assess patients experiencing unified way treat them integrated manner.

Language: Английский

Citations

0
Dynamic Lipidome Reorganization in Response to Heat Shock Stress DOI Open Access
Luis E. Solano, Uri Keshet,

Andrew Reinschmidt

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2843 - 2843

Published: March 21, 2025

The heat shock response (HSR) is a conserved cellular mechanism critical for adaptation to environmental and physiological stressors, with broad implications cell survival, immune responses, cancer biology. While the HSR has been extensively studied at proteomic transcriptomic levels, role of lipid metabolism membrane reorganization remains underexplored. Here, we integrate mass spectrometry-based lipidomics RNA sequencing characterize global lipidomic changes in HeLa cells exposed three conditions: control, (HS), HS eight hours recovery. Heat shock-induced extensive remodeling, including significant increases fatty acids, glycerophospholipids, sphingolipids, partial normalization during Transcriptomic analysis identified over 2700 upregulated 2300 downregulated genes under shock, GO enrichment suggesting potential transcriptional contributions metabolism. However, alone did not fully explain observed shifts, additional layers regulation. Joint pathway revealed glycerophospholipid sphingolipid metabolism, while network transport regulators (STAB2, APOB), stress-linked metabolic nodes (KNG1), persistent These findings provide comprehensive framework understanding lipid-mediated mechanisms highlight importance multi-omics integration stress disease

Language: Английский

Citations

0
Adverse childhood experiences (ACEs) and emotion dysregulation phenotypes: An intersectional analysis of race/ethnicity and gender in a nationally representative U.S. sample DOI
Xiaoyan Zhang, Gabriel J. Merrin, George M. Slavich

et al.

Child Abuse & Neglect, Journal Year: 2024, Volume and Issue: 158, P. 107129 - 107129

Published: Nov. 12, 2024

Language: Английский

Citations

1
California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience DOI Creative Commons
L. Kim, Sophia Miryam Schüssler‐Fiorenza Rose, Summer Mengelkoch

et al.

Stress, Journal Year: 2024, Volume and Issue: 27(1)

Published: Dec. 2, 2024

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes death the United States. Despite this fact, our mechanistic understanding how ACEs impact health is limited. Moreover, interventions for reducing stress use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed combined cross-sectional study randomized controlled trial, called California Stress, Trauma, Resilience Study (CalSTARS), to (a) characterize influence multisystem biological functioning adults with all levels ACE burden current perceived stress, using multiomics other complementary approaches, (b) test efficacy new Precision Intervention Stress (PRECISE) elevated who have experienced full range ACEs. The primary trial outcome secondary outcomes span variety psychological, emotional, biological, behavioral variables, as assessed self-report measures, wearable technologies, extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) will be subjected genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, metagenomic/microbiome analysis. In protocol paper, describe scientific gaps motivating well sample, design, procedures, planned analyses. Ultimately, goal leverage power cutting-edge tools from psychology, multiomics, precision medicine, translational bioinformatics identify social, molecular, immunological processes can targeted reduce stress-related disease risk enhance biopsychosocial resilience individuals communities worldwide.

Language: Английский

Citations

1
James German and the Quest to Understand Human RECQ Helicase Deficiencies DOI Creative Commons
Raymond J. Monnat

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1077 - 1077

Published: June 21, 2024

James German's work to establish the natural history and cancer risk associated with Bloom syndrome (BS) has had a strong influence on generation of scientists clinicians working understand other RECQ deficiencies heritable predisposition syndromes. I summarize by us others below, inspired precedents BS, compare BS deficiency syndromes focus Werner (WS). What we know, unanswered questions new opportunities are discussed, as potential ways treat or modify WS-associated disease mechanisms pathways.

Language: Английский

Citations

0
Stress tests and biomarkers of resilience: Proceedings of the second state of resilience science conference DOI Open Access
Cathleen Colón‐Emeric, Jeremy Walston, Alessandro Bartolomucci

et al.

Journal of the American Geriatrics Society, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

The "Stress Tests and Biomarkers of Resilience" conference, hosted by the American Geriatrics Society National Institute on Aging, marks second in a series aimed at advancing field resilience science. Held March 4-5, 2024, Bethesda, Maryland, this conference built upon foundational work from first which focused defining across various domains-physical, cognitive, psychosocial. This year's gathering centered around three factors: biology that underlies resilient outcomes; social, environmental, genetic, psychosocial factors impact biology; biomarker testing imaging predicts outcomes for older adults. presentations discussions these topics were underscored considerations many impacts social determinants health resiliency interventions, advances modern training research methodologies influence data collection experiment design.

Language: Английский

Citations

0
AMP-Activated Protein Kinase Treatment Ameliorates Chronic Restraint Stress Induced Memory Impairment in Early Adolescent Rat by Restoring Metabolite Profile and Synaptic Proteins DOI
Koilmani Emmanuvel Rajan,

Baskaran Nishanthini,

Swamynathan Sowndharya

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 50(1)

Published: Nov. 18, 2024

Language: Английский

Citations

0