Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex

Wang, Jiawei; Zhao, Hongyu; Girgenti, Matthew J.

doi:10.1016/j.biopsych.2021.02.012

Cited by 7 publications

(6 citation statements)

References 73 publications

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“…While occludin ( OCLN) is significantly increased in the MDD occipital cortex, no significant changes were detected in other TJs such as CLDN12 , tight junction protein 1 (ZO‐1), ZO‐2, and Platelet And Endothelial Cell Adhesion Molecule 1 (PECAM1) (Greene et al., 2020). Transcriptomic studies have looked at the PFC of PTSD patients to discover sex‐specific genomic signatures, but no work seems to include TJ genes specifically (Wang et al., 2021).…”

Section: A Role For Inflammation‐driven Leakiness Of Barriersmentioning

confidence: 99%

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Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Doney

Cadoret

Dion‐Albert

et al. 2021

Eur J of Neuroscience

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Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion‐related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post‐traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%–50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion‐related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation‐related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation‐driven leakiness of the blood–brain and gut barriers in emotion regulation and mood are highlighted. Stress‐induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut–brain axis which is central to production of mood‐related neurotransmitter serotonin. Novel therapeutic approaches such as anti‐inflammatory drugs, the fast‐acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder‐associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.

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Section: A Role For Inflammation‐driven Leakiness Of Barriersmentioning

confidence: 99%

“…Manic phase 1 (PECAM1) (Greene et al, 2020). Transcriptomic studies have looked at the PFC of PTSD patients to discover sexspecific genomic signatures, but no work seems to include TJ genes specifically (Wang et al, 2021).…”

mentioning

confidence: 99%

Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Doney

Cadoret

Dion‐Albert

et al. 2021

Eur J of Neuroscience

View full text Add to dashboard Cite

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“…The sex-specific transcriptional landscape, mainly in the cortex, has been recently reviewed in the context of PTSD [101]. The methodological heterogeneity across the studies selected in this review limited our ability to conduct well-powered region-specific and sex-specific Counts correspond to the number of convergent genes enriched in that pathway.…”

Section: Discussionmentioning

confidence: 99%

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review

Núñez-Rios¹,

Martínez‐Magaña²,

Nagamatsu³

et al. 2023

Complex Psychiatry

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Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly-understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrate brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, 17 of them significantly enriched for PTSD. Chemical-synaptic transmission and signaling by G-protein-coupled receptors (GPCRs) were consistently enriched in across -omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD’s pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

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“…Multiple studies reported PTSD-associated differences in immune markers based on sex (reviewed in ref. [108]). A gene coexpression study showed upregulation of an IL-12 signaling module in men but not women with PTSD [31].…”

Section: Alterations In Peripheral Immune Markers In Ptsdmentioning

confidence: 99%

“…In addition, Kim et al [110] reported sex-specific differences in peripheral blood leukocyte composition, as men but not women with lifetime PTSD have increased monocyte proportions. Evidence from post-mortem brain samples revealed decreased microglia proportions in women with PTSD [108,111]. The key factor underlying the sex-specific immune response in PTSD may be estrogen, as studies showed that lower estrogen levels are associated with increased PTSD symptoms [112,113].…”

Section: Alterations In Peripheral Immune Markers In Ptsdmentioning

confidence: 99%

The role of the immune system in posttraumatic stress disorder

et al. 2022

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Posttraumatic stress disorder (PTSD) develops in a subset of individuals upon exposure to traumatic stress. In addition to well-defined psychological and behavioral symptoms, some individuals with PTSD also exhibit elevated concentrations of inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Moreover, PTSD is often co-morbid with immune-related conditions, such as cardiometabolic and autoimmune disorders. Numerous factors, including lifetime trauma burden, biological sex, genetic background, metabolic conditions, and gut microbiota, may contribute to inflammation in PTSD. Importantly, inflammation can influence neural circuits and neurotransmitter signaling in regions of the brain relevant to fear, anxiety, and emotion regulation. Given the link between PTSD and the immune system, current studies are underway to evaluate the efficacy of anti-inflammatory treatments in those with PTSD. Understanding the complex interactions between PTSD and the immune system is essential for future discovery of diagnostic and therapeutic tools.

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Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex

Cited by 7 publications

References 73 publications

Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review

The role of the immune system in posttraumatic stress disorder

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