Brain Behavior and Immunity, Год журнала: 2018, Номер 74, С. 133 - 142
Опубликована: Сен. 4, 2018
Язык: Английский
Psychiatry and Clinical Neurosciences, Год журнала: 2019, Номер 73(4), С. 143 - 153
Опубликована: Янв. 17, 2019
While post-traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted link between this alterations in the immune inflammatory systems. Epidemiological studies have demonstrated that PTSD associated with significantly increased rates physical comorbidities which dysregulation involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, autoimmune diseases. In line this, number blood biomarker reported compared to healthy controls, individuals exhibit elevated levels proinflammatory markers, interleukin-1β, interleukin-6, tumor necrosis factor-α, C-reactive protein. Moreover, various lines animal human research suggested inflammation not only but also can play an important role its pathogenesis pathophysiology. review, we first summarize suggestive PTSD. We then examine findings suggest possible mechanisms terms two different interrelated perspectives: putative causes activities potential consequences generates. Given there dearth treatment options for PTSD, possibilities new therapeutic approaches using pharmacological non-pharmacological treatments/interventions anti-inflammatory effects are discussed. Despite increasing attention given pathology remains much be elucidated, including more detailed inflammation, usefulness biomarkers diagnostic prognostic efficacy novel strategies targeting inflammation.
Язык: Английский
Процитировано
320
World Psychiatry, Год журнала: 2023, Номер 22(2), С. 236 - 262
Опубликована: Май 9, 2023
The field of psychiatry is hampered by a lack robust, reliable and valid biomarkers that can aid in objectively diagnosing patients providing individualized treatment recommendations. Here we review critically evaluate the evidence for most promising psychiatric neuroscience literature autism spectrum disorder, schizophrenia, anxiety disorders post‐traumatic stress major depression bipolar substance use disorders. Candidate reviewed include various neuroimaging, genetic, molecular peripheral assays, purposes determining susceptibility or presence illness, predicting response safety. This highlights critical gap biomarker validation process. An enormous societal investment over past 50 years has identified numerous candidate biomarkers. However, to date, overwhelming majority these measures have not been proven sufficiently reliable, useful be adopted clinically. It time consider whether strategic investments might break this impasse, focusing on limited number candidates advance through process definitive testing specific indication. Some N170 signal, an event‐related brain potential measured using electroencephalography, subgroup identification within disorder; striatal resting‐state functional magnetic resonance imaging (fMRI) measures, such as connectivity index (SCI) abnormalities (FSA) index, prediction schizophrenia; error‐related negativity (ERN), electrophysiological first onset generalized structural connectomic social disorder. Alternate forms classification may conceptualizing Collaborative efforts allowing inclusion biosystems beyond genetics neuroimaging are needed, online remote acquisition selected naturalistic setting mobile health tools significantly field. Setting benchmarks well‐defined target application, along with development appropriate funding partnership mechanisms, would also crucial. Finally, it should never forgotten that, actionable, will need clinically predictive at individual level viable clinical settings.
Язык: Английский
Процитировано
156
Translational Psychiatry, Год журнала: 2022, Номер 12(1)
Опубликована: Авг. 4, 2022
Abstract Posttraumatic stress disorder (PTSD) develops in a subset of individuals upon exposure to traumatic stress. In addition well-defined psychological and behavioral symptoms, some with PTSD also exhibit elevated concentrations inflammatory markers, including C-reactive protein, interleukin-6, tumor necrosis factor-α. Moreover, is often co-morbid immune-related conditions, such as cardiometabolic autoimmune disorders. Numerous factors, lifetime trauma burden, biological sex, genetic background, metabolic gut microbiota, may contribute inflammation PTSD. Importantly, can influence neural circuits neurotransmitter signaling regions the brain relevant fear, anxiety, emotion regulation. Given link between immune system, current studies are underway evaluate efficacy anti-inflammatory treatments those Understanding complex interactions system essential for future discovery diagnostic therapeutic tools.
Язык: Английский
Процитировано
86
Science, Год журнала: 2024, Номер 384(6698)
Опубликована: Май 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.
Язык: Английский
Процитировано
21
Molecular Psychiatry, Год журнала: 2019, Номер 25(12), С. 3337 - 3349
Опубликована: Сен. 10, 2019
Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, limitations identifying those at risk. Prior studies suggest that PTSD may a systemic illness, affecting not just the brain, entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, organism-level physiological changes. Identification these could aid diagnostics, treatment decision-making, risk evaluation. In search for diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, clinical features from three cohorts male veterans. discovery cohort 83 warzone-related cases 82 warzone-exposed controls, identified set 343 candidate biomarkers. These biomarkers were selected an integrated approach using (1) data-driven methods, Support Vector Machine with Recursive Feature Elimination other standard or published methodologies, (2) hypothesis-driven approaches, previous genetic polygenic risk, PTSD-related literature. After reassessment ~30% participants, refined this markers 28, based on their performance ability track changes phenotype time. The final panel 28 was validated independent (26 cases, 26 controls) good (AUC = 0.80, 81% accuracy, 85% sensitivity, 77% specificity). identification validation diverse represents powerful novel improve accuracy reduce bias diagnosing combat-related PTSD.
Язык: Английский
Процитировано
92
Brain Behavior and Immunity, Год журнала: 2019, Номер 84, С. 180 - 199
Опубликована: Ноя. 27, 2019
Язык: Английский
Процитировано
78
Genes Brain & Behavior, Год журнала: 2020, Номер 19(3)
Опубликована: Янв. 28, 2020
More than two-thirds of patients suffering from stress-related disorders are women but over suicide completers men. These just some examples the many sex differences in prevalence and manifestations disorders, such as major depressive disorder, post-traumatic stress anxiety which have been extensively documented clinical research. Nonetheless, molecular origins this dimorphism still quite obscure. In response to lack knowledge, NIH recently advocated implementing biological variable design preclinical studies across disciplines. As a result, newly emerging field within psychiatry is trying elucidate causes underlying clinically described dimorphism. Several rodents humans already identified genes that regulated by acute chronic sex-specific fashion. Furthermore, current transcriptomic shown pathways networks male female individuals not equally affected exposure. review, we give an overview transcriptional designed understand how influences stress-specific changes rodent models, well human psychiatric patients, highlighting use different methodological techniques. Understanding mechanisms more males, females, may lead identification mechanisms, their selective contribution susceptibility, role development disorders.
Язык: Английский
Процитировано
73
Sleep Medicine Reviews, Год журнала: 2022, Номер 63, С. 101623 - 101623
Опубликована: Март 12, 2022
Язык: Английский
Процитировано
52
Nature Neuroscience, Год журнала: 2022, Номер 25(11), С. 1434 - 1445
Опубликована: Окт. 20, 2022
Abstract Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute individual clinical outcomes is unknown. Here, we compared transcriptional responses hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD ( n = 19 hiPSC 20 PBMC donors) controls donors). In only, observed diagnosis-specific glucocorticoid-induced changes gene expression corresponding PTSD-specific transcriptomic patterns found postmortem brains. We glucocorticoid hypersensitivity neurons, identified genes that this PTSD-dependent response. find evidence of a coregulated network transcription mediates hyper-responsivity PTSD. These findings suggest represent platform for examining molecular mechanisms underlying PTSD, identifying biomarkers response, conducting drug screening identify new therapeutics.
Язык: Английский
Процитировано
41
Neurobiology of Stress, Год журнала: 2022, Номер 18, С. 100455 - 100455
Опубликована: Апрель 23, 2022
'You can't roll the clock back and reverse effects of experiences' Bruce McEwen used to say when explaining how allostasis labels adaptive process. Here we will for once times that science glucocorticoid hormone was honored with a Nobel prize highlight discovery their receptors in hippocampus as inroad its current status master regulator control stress coping adaptation. Glucocorticoids operate concert numerous neurotransmitters, neuropeptides, other hormones aim facilitate processing information neurocircuitry stress, from anticipation perception novel experience behavioral adaptation memory storage. This action, exerted by glucocorticoids, is guided two complementary receptor systems, mineralocorticoid (MR) (GR), need be balanced healthy response pattern. discuss cellular, neuroendocrine, studies underlying MR:GR balance concept, relevance hypothalamic-pituitary-adrenal (HPA) -axis patterns note limited understanding yet sexual dimorphism actions. We conclude prospect (i) genetically epigenetically regulated variants dictate cell-type-specific transcriptome signatures stress-related neuropsychiatric symptoms (ii) selective modulators are becoming available more targeted treatment. These new developments may help 'restart clock' support resilience.
Язык: Английский
Процитировано
38