Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts DOI Creative Commons
Şeyma Katrinli, Agaz H. Wani, Adam X. Maihofer

et al.

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 18, 2024

Abstract Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, impact trauma, or sequelae PTSD itself. These effects include in DNA methylation (DNAm), an important form epigenetic gene regulation, at multiple CpG loci across genome. Moreover, these be shared specific both central and peripheral tissues. Here, we aim identify blood DNAm characterize underlying mechanisms by examining extent which they mirror associations brain regions. Methods As Psychiatric Genomics Consortium (PGC) Epigenetics Workgroup, conducted largest cross-sectional meta-analysis epigenome-wide association studies (EWASs) date, involving 5077 participants (2156 cases 2921 trauma-exposed controls) from 23 civilian military studies. diagnosis assessments were harmonized standardized guidelines established PGC-PTSD Workgroup. was assayed using Illumina HumanMethylation450 MethylationEPIC (850 K) BeadChips. Within each cohort, regressed on sex (if applicable), age, cell proportions, ancestry. An inverse variance-weighted performed. We replication analyses tissue regions, neuronal nuclei, cellular model prolonged stress. Results identified 11 sites overall (1.44e − 09 < p 5.30e 08), as well 14 strata (military vs sex, ancestry), including CpGs AHRR CDC42BPB . Many exhibit blood–brain correlation levels cross-tissue Out 9 annotated expressed blood, 5 showed significant correlations expression their respective genes. Conclusions This study identifies PTSD-associated leverages data postmortem samples, GWAS, genome-wide interpret biology prioritize genes whose regulation differs those PTSD.

Language: Английский

A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex DOI
Louise A. Huuki-Myers, Abby Spangler, Nicholas J. Eagles

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6698)

Published: May 23, 2024

The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions domains. Using PsychENCODE publicly available data, we mapped enrichment types genes associated neuropsychiatric disorders discrete

Language: Английский

Citations

20
Regulation of Stress-Induced Immunosuppression in the Context of Neuroendocrine, Cytokine, and Cellular Processes DOI Creative Commons
Evgenii I. Balakin, Kseniya A. Yurku, M. V. Ivanov

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(1), P. 76 - 76

Published: Jan. 15, 2025

Understanding the regulatory mechanisms of stress-induced immunosuppression and developing reliable diagnostic methods are important tasks in clinical medicine. This will allow for development effective strategies prevention treatment conditions associated with immune system dysfunction induced by chronic stress. The purpose this review is to conduct a comprehensive analysis synthesis existing data on immunosuppression. aimed at identifying key neuroendocrine, cytokine, cellular processes underlying suppression response under study involved search scientific literature covering cellular, molecular regulation, as well modern its diagnosis. Major international bibliographic databases publications biomedicine, psychophysiology, immunology were selected search. results identified regulating reviewed provided detailed descriptions neuroendocrine cytokine A significant portion confirms that activation hypothalamic-pituitary-adrenal (HPA) axis subsequent elevation cortisol levels exert substantial immunosuppressive effects cells, particularly macrophages lymphocytes, leading innate adaptive responses. also highlight crucial role catecholamines (adrenaline noradrenaline) initiating

Language: Английский

Citations

1
1,2,4-Trimethoxybenzene ameliorates depression-like behaviors by inhibiting the activation of NLRP3 inflammasome DOI
Yang Zhang,

Na Che,

Bo Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114361 - 114361

Published: March 2, 2025

Language: Английский

Citations

1
Psychedelic control of neuroimmune interactions governing fear DOI
Elizabeth N. Chung, Jinsu Lee, Carolina Manganeli Polonio

et al.

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

Published: April 23, 2025

Language: Английский

Citations

1
Transcriptomic analysis of the human habenula in schizophrenia DOI Creative Commons
Ege A Yalcinbas, Bukola Ajanaku, Erik D. Nelson

et al.

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

Published: Feb. 27, 2024

Abstract Pathophysiology of many neuropsychiatric disorders, including schizophrenia (SCZD), is linked to habenula (Hb) function. While pharmacotherapies and deep brain stimulation targeting the Hb are emerging as promising therapeutic treatments, little known about cell type-specific transcriptomic organization human or how it altered in SCZD. Here we define molecular neuroanatomy identify changes individuals with SCZD compared neurotypical controls. Utilizing Hb-enriched postmortem tissue, performed single nucleus RNA-sequencing (snRNA-seq; n=7 donors) identified 17 molecularly defined types across 16,437 nuclei, 3 medial 7 lateral populations, several which were conserved between rodents humans. Single molecule fluorescent situ hybridization (smFISH; n=3 validated snRNA-seq mapped their spatial locations. Bulk type deconvolution tissue from 35 33 controls yielded 45 SCZD-associated differentially expressed genes (DEGs, FDR < 0.05), 32 (71%) unique tissue. eQTL analysis 717 independent SNP-gene pairs (FDR where either SNP a risk variant (16 pairs) gene DEG (7 pairs). colocalization 16 colocalized genes. These results topographically organized distinct signatures demonstrate genetic associated SCZD, thereby providing novel insights into role disorders. One Sentence Summary Transcriptomic identification illness state.

Language: Английский

Citations

4
Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models DOI Creative Commons
Raül Andero

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Most of the fear literature on humans and animals tests healthy individuals. However, memories can differ between individuals those previously exposed to traumatic stress, such as a car accident, sexual abuse, military combat personal assault. Traumatic stress lead post-traumatic disorder (PTSD) which presents alterations in memories, an impairment extinction recall. PTSD-like animal models are single highly stressful experience laboratory, immobilization or single-prolonged stress. Some days later, model be tested procedures that help uncover molecular mechanisms memories. In this review, there discussed stress-induced patients with PTSD models. The focus is effects estradiol cortisol/corticosterone hormones different genes, FKBP prolyl isomerase 5 gene (FKBP5) - FK506 binding protein 51 (FKBP51), pituitary adenylate cyclase-activating peptide (PACAP) polypeptide type I receptor (PAC1R), endocannabinoid (eCB) system tropomyosin kinase B (TrkB) brain-derived neurotrophic factor (BDNF). conclusion greater emphasis should placed investigating PTSD, through direct testing use relevant

Language: Английский

Citations

0
AI as an accelerator for defining new problems that transcends boundaries DOI Creative Commons
Tayo Obafemi-Ajayi,

Steven Jennings,

Yu Zhang

et al.

BioData Mining, Journal Year: 2025, Volume and Issue: 18(1)

Published: Feb. 18, 2025

Interdisciplinary, transdisciplinary, convergence, and No-Boundary Thinking (NBT) research are methodology technology-agnostic approaches to problem solving. The focus is on defining problems informed by access multiple knowledge sources expert perspectives across different domains, with the goal of accessing all available perspectives. While could be seen as a difficult attain objective, recent rise AI we might closer approaching this goal. We review several examples methodologies technologies that have been used put these strategies into action, but primary paper how advances in now enable quantum leap forward new problems. By leveraging capacity synthesize from tools can propose candidate definitions. uniquely able draw upon many more than any individual-or even very large team-could. Coupled human intelligence, better defined address complex scholarly or societal challenges.

Language: Английский

Citations

0
Corticosteroid‐regulated gene transcription in SH‐SY5Y‐derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor‐mediated response DOI Open Access

Justina F. Lugenbühl,

Clara Snijders,

Cameron D. Pernia

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Post‐traumatic stress disorder (PTSD) and major depressive (MDD) are debilitating stress‐related psychiatric disorders that can develop following exposure to traumatic events or chronic in some individuals. The neurobiological processes leading disease remain largely unknown. Among others, these characterized by a dysregulated hypothalamic–pituitary–adrenal axis, which is regulated the glucocorticoid receptor (GR) mineralocorticoid (MR). This leads altered downstream corticosteroid‐induced gene expression. In vitro models promising tools investigate specific underpinnings of response brain. Here, we investigated suitability SH‐SY5Y‐derived neurons as cost‐efficient system study role GR MR neuronal response. were characterized, exposed corticosteroids, analyzed on transcriptomic proteomic levels. We show (i) express sufficient seemingly functional allow transcription, (ii) three corticosteroids cortisol, dexamethasone, aldosterone, induced similar effects, (iii) antagonist spironolactone mildly attenuated effects dexamethasone FKBP5 , DUSP1 SUPV3L1 . Mifepristone did not significantly alter effect aldosterone. (iv) Integrating alterations corticosteroid‐exposed with those iPSC‐derived showed concordant two systems. To determine translational validity, compared expression transcriptome postmortem brain samples from individuals PTSD MDD, yielding stronger negative correlations corticosteroid signatures than MDD signatures. Upon further refinement validation, may serve simplistic tool implicated molecular networks around MR. Strengthening our insight into receptors' functions improves understanding commonly such MDD.

Language: Английский

Citations

0
Epigenetic factors in posttraumatic stress disorder resilience and susceptibility DOI Creative Commons
Majeed M. A. Ali,

Ibrahim El Tantawy El Sayed,

Yuliang Wang

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 20, 2025

Abstract Background Posttraumatic stress disorder (PTSD) affects approximately 8% of the US population, with varying susceptibility among individuals exposed to trauma. While genetic factors contribute PTSD risk, emerging evidence suggests that epigenetic mechanisms play a crucial role in translating environmental exposures into lasting neurobiological changes. Purpose This review provides comprehensive analysis cutting-edge research on PTSD, particular emphasis novel findings regarding resilience and mechanisms. We explore recent technological advances their applications understanding pathophysiology. Main body Advanced epigenomic approaches have revealed complex interactions between DNA methylation, histone modifications, non-coding RNAs PTSD. Novel highlight cell type-specific signatures temporal dynamics following trauma exposure. Single-cell studies identified previously unknown cellular heterogeneity responses. Recent data modifications not only influence individual but may also transgenerational transmission effects. Integrative multi-omics new insights molecular networks underlying vulnerability. Conclusion unprecedented complexity These open avenues for personalized interventions based profiles suggest therapeutic strategies targeting modifications. enhanced has significant implications risk assessment, prevention, treatment. Graphical abstract

Language: Английский

Citations

0
Should Inflammation Be a Specifier for Major Depression in the DSM-6? DOI
Manish K. Jha, Marion Leboyer, Carmine M. Pariante

et al.

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

This Viewpoint discusses the opportunity to include inflammatory biomarkers as specifiers for major depression in upcoming Sixth Edition of Diagnostic and Statistical Manual Mental Disorders ( DSM-6 ).

Language: Английский

Citations

0