Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD DOI Creative Commons
Mark W. Logue, Zhenwei Zhou, Filomene G. Morrison

и другие.

Neurobiology of Stress, Год журнала: 2021, Номер 15, С. 100398 - 100398

Опубликована: Сен. 20, 2021

Studies evaluating neuroimaging, genetically predicted gene expression, and pre-clinical genetic models of PTSD, have identified PTSD-related abnormalities in the prefrontal cortex (PFC) brain, particularly dorsolateral ventromedial PFC (dlPFC vmPFC). In this study, RNA sequencing was used to examine expression dlPFC vmPFC using tissue from VA National PTSD Brain Bank donors with histories or without depression n = 38, 35), cases (n 32), psychopathology-free controls 24, 20). Analyses compared controls. Follow-up analyses contrasted Twenty-one genes were differentially expressed after strict multiple testing correction. PTSD-associated roles learning memory (FOS, NR4A1), immune regulation (CFH, KPNA1) myelination (MBP, MOBP, ERMN) identified. partially overlapped depression-associated genes. Co-expression network networks enriched for immune-related across two brain regions. However, association patterns distinct. The IL1B significantly associated candidate-gene analysis an upstream regulator both There evidence replication associations independent cohort a recent strong correlation between effect sizes significant studies (r 0.66, p < 2.2 × 10−16). conclusion, study several novel region specific networks.

Язык: Английский

Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits DOI
Kerry J. Ressler, Sabina Berretta, Vadim Y. Bolshakov

и другие.

Nature Reviews Neurology, Год журнала: 2022, Номер 18(5), С. 273 - 288

Опубликована: Март 29, 2022

Язык: Английский

Процитировано

251
Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program DOI
Murray B. Stein, Daniel F. Levey, Zhongshan Cheng

и другие.

Nature Genetics, Год журнала: 2021, Номер 53(2), С. 174 - 184

Опубликована: Янв. 28, 2021

Язык: Английский

Процитировано

195
The role of the immune system in posttraumatic stress disorder DOI Creative Commons
Şeyma Katrinli, Nayara Cristina dos Santos Oliveira, Jennifer C. Felger

и другие.

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

84
Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder DOI
Caroline M. Nievergelt, Adam X. Maihofer, Elizabeth G. Atkinson

и другие.

Nature Genetics, Год журнала: 2024, Номер 56(5), С. 792 - 808

Опубликована: Апрель 18, 2024

Язык: Английский

Процитировано

49
Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood DOI
Nikolaos P. Daskalakis, Artemis Iatrou, Chris Chatzinakos

и другие.

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
Beyond the neuron: Role of non-neuronal cells in stress disorders DOI Creative Commons
Flurin Cathomas, Leanne M. Holt, Eric M. Parise

и другие.

Neuron, Год журнала: 2022, Номер 110(7), С. 1116 - 1138

Опубликована: Фев. 18, 2022

Язык: Английский

Процитировано

46
Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression DOI Creative Commons
Carina Seah, Michael S. Breen,

Tom Rusielewicz

и другие.

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

40
Mineralocorticoid receptor and glucocorticoid receptor work alone and together in cell-type-specific manner: Implications for resilience prediction and targeted therapy DOI Creative Commons
Nikolaos P. Daskalakis, Onno C. Meijer, E. R. de Kloet

и другие.

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
Genetic insights into the neurobiology of anxiety DOI Creative Commons
Maija-Kreetta Koskinen, Iiris Hovatta

Trends in Neurosciences, Год журнала: 2023, Номер 46(4), С. 318 - 331

Опубликована: Фев. 22, 2023

Anxiety and fear are evolutionarily conserved emotions that increase the likelihood of an organism surviving threatening situations. vigilance states regulated by neural networks involving multiple brain regions. In anxiety disorders, this intricate regulatory system is disturbed, leading to excessive or prolonged fear. disorders have both genetic environmental risk factors. Genetic research has potential identify specific variants causally associated with phenotypes. recent decades, genome-wide association studies (GWASs) revealed predisposing neuropsychiatric suggesting novel neurobiological pathways in etiology these disorders. Here, we review human GWASs anxiety-like behavior rodent models. These paving way for a better understanding mechanisms underlying

Язык: Английский

Процитировано

32
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments DOI Creative Commons
John H. Krystal, Alfred P. Kaye, Sarah Jefferson

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(49)

Опубликована: Ноя. 27, 2023

Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy treatment-resistant symptoms, protection against relapse distinguish it from prior antidepressants. discovery reconceptualization the neurobiology depression and, in turn, insights elaboration its mechanisms action inform studies pathophysiology related disorders. It been 25 y since we first presented our ketamine findings Thus, is timely this review to consider what have learned suggest future directions optimization rapid-acting antidepressant treatment.

Язык: Английский

Процитировано

30