Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood

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

Published: May 23, 2024

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided underlying genomic structure. Single RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) non-neuronal cell types. Analyses brain-blood intersections >50,000 UK Biobank participants were conducted along with fine-mapping results PTSD MDD genome-wide association studies distinguish risk from processes. data suggest shared distinct both propose potential therapeutic targets biomarkers.

Language: Английский

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Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study

Nature Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

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The Landscape of Shared and Divergent Genetic Influences across 14 Psychiatric Disorders

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

Published: Jan. 15, 2025

Abstract Psychiatric disorders display high levels of comorbidity and genetic overlap 1,2 . Genomic methods have shown that even for schizophrenia bipolar disorder, two long-thought to be etiologically distinct 3 , the majority signal is shared 4 Furthermore, recent cross-disorder analyses uncovered over a hundred pleiotropic loci across eight 5 However, full scope disorder-specific basis psychopathology remains largely uncharted. Here, we address this gap by triangulating suite cutting-edge statistical functional genomic applied 14 childhood- adult-onset psychiatric (1,056,201 cases). Our identify characterize five underlying factors 6 explain variance individual (∼66% on average) are associated with 268 loci. We observed particularly polygenic 7 local correlation 8 very few 9 defined by: ( i ) disorder (“SB factor”), ii major depression, PTSD, anxiety (“internalizing factor”). At level, multiple 10–12 which demonstrated SB factor was substantially enriched in genes expressed excitatory neurons, whereas internalizing oligodendrocyte biology. By comparison, all broad biological processes (e.g., transcriptional regulation). These results indicate increasing differentiation function at different risk, from quite general vulnerability more specific pathways subsets disorders. observations may inform neurobiologically valid nosology implicate novel targets therapeutic developments designed treat commonly occurring comorbid presentations.

Language: Английский

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cAMP-PKA signaling pathway and anxiety: Where do we go next?

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111311 - 111311

Published: July 24, 2024

Language: Английский

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Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 333, P. 118425 - 118425

Published: June 5, 2024

Language: Английский

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Comprehensive view of suicide: A neuro-immune-endocrine approach

World Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 15(2)

Published: Jan. 14, 2025

Suicide is defined as the act of a person attempting to take their own life by causing death. complex phenomenon that influenced multitude factors, including psychosocial, cultural, and religious aspects, well genetic, biochemical, environmental factors. From biochemical perspective, it crucial consider communication between endocrine, immune, nervous systems when studying etiology suicide. Several pathologies involve bidirectional peripheral activity central system action molecules such cytokines, hormones, neurotransmitters. These humoral signals, present in optimal quantities, are responsible for maintaining physiological homeostasis, mood states. Stress elevates cortisol proinflammatory cytokines levels alter neurotransmitters balance, thereby increasing risk developing psychiatric disorder subsequently suicidal behavior. This review provides an integrative perspective about neurochemical, immunological, endocrinological disturbances associated with behavior, particular focus on those alterations may serve potential markers and/or indicators state preceding tragic act.

Language: Английский

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Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models

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

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Observational and Genetic Analyses of Traumatic Experiences and Endometriosis

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

Published: Feb. 5, 2025

Importance Although psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition. Objective To examine relationship between traumatic experiences endometriosis using observational genetically informed analyses. Design, Setting, Participants For this case-control study, analyses were performed May 13, 2023, September 30, 2024. Genotypic phenotypic was combined from UK Biobank individual-level data (up to 8276 patients 240 117 female controls) genome-wide a large meta-analysis (European ancestry: 21 779 449 087 controls; East Asian 1713 1581 FinnGen cohort (16 588 111 583 controls European descent). Main Outcomes Measures Phenotypic associations via multiple regression; latent-class analysis (LCA) investigate co-occurrence patterns different in cases correlation polygenic risk scoring (PRS) assess pleiotropy linking events endometriosis. Results Up women (mean [SD] age, 53.2 [13.0] years) 56.5 [9.6] investigated study. Women more likely report childhood adulthood stressful (eg, contact odds ratio [OR], 1.28; 95% CI, 1.02-1.26). Our LCA highlighted association emotional physical (225 [8%] vs 3948 [5%]; P < 2.2 × 10 −16 ) sexual (414 [5%] 3158 [4%]; = 2.9 −3 ). Unaffected (controls) assigned “no trauma” latent class (563 [20%] 18 949 [24%]; 7.4 −14 (rg) linked trauma-related outcomes, including posttraumatic stress disorder (meta-analysis rg 0.31, 7.1 ; 0.26, 4.7 −15 maltreatment 0.23, 1.3 −6 0.16, 1 −4 Endometriosis PRS increased disease (β ), but no interaction observed types events. Conclusions Relevance The present study comprehensively impact on In particular, our findings highlight potential which appears be independent

Language: Английский

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The impact of trauma and how to intervene: a narrative review of psychotraumatology over the past 15 years

European journal of psychotraumatology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

To mark 15 years of the European Journal Psychotraumatology, editors reviewed past 15-year research on trauma exposure and its consequences, as well developments in (early) psychological, pharmacological complementary interventions. In all sections this paper, we provide perspectives sex/gender aspects, life course trends, cross-cultural/global systemic societal contexts. Globally, majority people experience stressful events that may be characterized traumatic. However, definitions what is traumatic are not necessarily straightforward or universal. Traumatic have a wide range transdiagnostic mental physical health limited to posttraumatic stress disorder (PTSD). Research genetic, molecular, neurobiological influences show promise for further understanding underlying risk resilience trauma-related consequences. Symptom presentation, prevalence, course, response experiences, differ depending individuals' age developmental phase, sex/gender, sociocultural environmental contexts, socio-political forces. Early interventions potential prevent acute reactions from escalating PTSD diagnosis whether delivered golden hours weeks after trauma. prevention still scarce compared treatment where several evidence-based complementary/ integrative exist, novel forms delivery become available. Here, focus how best address negative outcomes following trauma, serve individuals across spectrum, including very young old, include considerations ethnicity, culture diverse beyond Western, Educated, Industrialized, Rich, Democratic (WEIRD) countries. We conclude with providing directions future aimed at improving well-being impacted by around world. The EJPT webinar provides 90-minute summary paper can downloaded here [http://bit.ly/4jdtx6k].

Language: Английский

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Telomere Dynamics in Post-Traumatic Stress Disorder: A Critical Synthesis

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 507 - 507

Published: Feb. 18, 2025

Post-traumatic stress disorder (PTSD), a mental caused by exposure to traumatic stress, affects 5-10% of the world's population. There is some evidence that PTSD associated with accelerated cellular aging, leading an increased risk medical and neurodegenerative comorbidities. Alterations in telomere length (TL) telomerase enzyme activity have been proposed as biomarkers this process. This hypothesis was seemingly confirmed preliminary research, but more recent studies yielded mixed results. The current narrative review conducted provide critical synthesis existing research on PTSD. Data from 26 clinical suggest TL highly variable may be influenced methodological, demographic, trauma-related, psychosocial factors. no for altered In contrast, animal suggests does lead shortening. Overall, it likely not, itself, reliable biomarker aging Other markers senescence, such epigenetic changes, prove specific measuring process patients

Language: Английский

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