Transcriptomic Organization of Human Posttraumatic Stress Disorder

Girgenti, Matthew J.; Wang, Jiawei; Ji, Dingjue; Cruz, Dianne A.; Stein, Murray B.; Young, Keith A.; Huber, Bertrand R.; Williamson, Douglas E.; Friedman, Matthew J.; Krystal, John H.; Zhao, Hongyu; Duman, Ronald S.

doi:10.1101/2020.01.27.921403

Cited by 8 publications

(25 citation statements)

References 81 publications

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“…These data demonstrate that exposure to the predator odor TMT induces both early (6 hours and 2 days) and late (4 weeks) gene expression changes related to stress and excitatory synaptic function. Among other targets, TMT exposure affected brain gene expression of FKPB5, GRM5, and CNR1, which have all been implicated in PTSD 16,20,22 . Furthermore, most differentially expressed genes were observed at late (20.9%) compared to early time points (4.7-7.0%; Figure 6).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, PTSD is associated with altered FKBP5 transcription and functionally relevant changes in FKBP5-GR complex 16,43 . These data suggest that the TMT exposure model of stress could be used to investigate the role of FKBP5 in both early and late effects of traumatic stress.…”

Section: Discussionmentioning

confidence: 99%

“…Sex differences in response to predator odor are documented 60 and women suffer from PTSD at three times the rate of men 3,16 . Therefore, future work should examine sex differences in response to TMT stress.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of cortisol to the GR downregulates corticotropin releasing factor (CRF) expression in the hypothalamus, acting as a negative feedback of HPA-axis activation 13 . Interestingly, in PTSD participants, the FK506 binding protein 5 (FKBP5), a chaperone protein that affects GR and mineralocorticoid receptor (MR) binding sensitivity for glucocorticoids and inhibits cellular translocation, is differentially expressed in several RNA sequencing studies compared to control participants both in peripheral blood cells, and post-mortem PFC brain tissue 14,15,16 . Together, these data provide strong support for the hypothesis that PTSD is associated with a persistent dysregulation in the canonical HPA-axis stress system 4 .…”

Section: The American Psychiatricmentioning

confidence: 99%

“…The goal of the present work was to assess early (6 hours and 2 days) and late (4 weeks) gene expression changes throughout the brain following TMT stress exposure. Gene expression analyses focused on stress/HPA-axis function and excitatory neurotransmission-related targets supported by clinical data 1,16,17,20 . Stress-related genes included NR3C1 (encodes for GR), NR3C2 (encodes for MR), FKBP5, and CRF.…”

Section: The American Psychiatricmentioning

confidence: 99%

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Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

Tyler

Weinberg

Lovelock

et al. 2020

Preprint

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Persistent changes in brain stress and glutamatergic function are associated with post-traumatic stress disorder (PTSD). Rodent exposure to the predator odor trimethylthiazoline (TMT) is an innate stressor that produces lasting behavioral consequences relevant to PTSD. As such, the goal of the present study was to assess early (6 hours and 2 days) and late (4 weeks) changes to gene expression (RT-PCR) related to stress and excitatory function following TMT exposure in male, Long-Evans rats. During TMT exposure, rats engaged in stress reactive behaviors, including digging and immobility. Further, the TMT group displayed enhanced exploration and mobility in the TMT-paired context one week after exposure, suggesting a lasting contextual reactivity. Gene expression analyses revealed upregulated FKBP5 6 hours post-TMT in the hypothalamus and dorsal hippocampus. Two days after TMT, GRM3 was downregulated in the prelimbic cortex and dorsal hippocampus, but upregulated in the nucleus accumbens. This may reflect an early stress response (FKBP5) that resulted in later glutamatergic adaptation (GRM3).Finally, four weeks after TMT exposure, several differentially expressed genes known to mediate excitatory tripartite synaptic function were observed. Specifically in the prelimbic cortex (GRM5, DLG4 and SLC1A3 upregulated), infralimbic cortex (GRM2 downregulated, Homer1 upregulated), nucleus accumbens (GRM7 and SLC1A3 downregulated), dorsal hippocampus (FKBP5 and NR3C2 upregulated, SHANK3 downregulated) and ventral hippocampus (CNR1, GRM7, GRM5, SHANK3, and Homer1 downregulated). These data demonstrate that TMT exposure stress induces early and late stress and excitatory molecular adaptations, which may help us understand the persistent glutamatergic dysfunction observed in PTSD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The American Psychiatricmentioning

confidence: 99%

Section: The American Psychiatricmentioning

confidence: 99%

See 3 more Smart Citations

Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

Tyler

Weinberg

Lovelock

et al. 2020

Preprint

View full text Add to dashboard Cite

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TOXGB: Teamwork Optimization Based XGBoost model for early identification of post-traumatic stress disorder

Gupta

Goel²,

Singh

et al. 2022

Cogn Neurodyn

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Post-traumatic stress (PTSD) is considered a clinical issue that influences numerous people from diverse trades all over the world. Numerous research scholars recorded diverse complexities to estimate the severity of the PTSD symptoms in the patients. But diagnosing PTSD and obtaining accurate diagnosing techniques becomes a more complicated task. Therefore, this paper develops a speech based post-traumatic stress disorder monitoring method and the significant objective of the proposed method is to determine if the patients are affected by PTSD. The proposed approach utilizes three different steps: pre-processing or pre-emphasis, feature extraction as well as classification to evaluate the patients affected by PTSD or not. The input speech signal is initially provided to the pre-processing phase where the speech gets segmented into frames. The speech frame is then extracted and classified using XGBoost based Teamwork optimization (XGB-TWO) algorithm. In addition to this, we utilized two different types of datasets namely TIMIT and FEMH to evaluate and classify the PSTD from the speech signals. Furthermore, based on the evaluation of the proposed model to diagnose PTSD patients, various evaluation metrics namely accuracy, specificity, sensitivity, and recall are evaluated. Finally, the experimental investigation and comparative analysis are carried out and the evaluation results demonstrated that the accuracy rate achieved for the proposed technique is 98.25%.

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Neural Transcriptomic Analysis of Sex Differences in Autism Spectrum Disorder: Current Insights and Future Directions

Kissel

Werling

2022

Biological Psychiatry

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Autism spectrum disorder (ASD) is consistently diagnosed 3 to 5 times more frequently in males than females, a dramatically sex-biased prevalence that suggests the involvement of sex-differential biological factors in modulating risk. The genomic scale of transcriptomic analyses of human brain tissue can provide an unbiased approach for identifying genes and associated functional processes at the intersection of sex-differential and ASD-impacted neurobiology. Several studies characterizing gene expression changes in the ASD brain have been published in recent years with increasing sample size and cellular resolution. These studies report several convergent patterns across data sets and genetically heterogeneous samples in the ASD brain, including elevated expression of gene sets associated with glial and immune function, and reduced expression of gene sets associated with neuronal and synaptic functions. Assessment of neurotypical cortex tissue has reported parallel patterns by sex, with male-elevated expression of overlapping sets of glial/immune-related genes and female-biased expression of neuronassociated genes, suggesting potential roles for these cell types in sex-differential ASD risk mechanisms. However, validating and further exploring these mechanisms is challenged by the available data, as existing studies of ASD brain include a limited number of female ASD donors and focus predominantly on cortex regions not known to show pronounced sex-differential morphology or function. With this review, we summarize convergent findings from several landmark studies of the transcriptome in ASD brain and their relationship to sex-differential gene expression, and we discuss limitations and remaining questions regarding transcriptomic analysis of sex differences in ASD.

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Transcriptomic Organization of Human Posttraumatic Stress Disorder

Cited by 8 publications

References 81 publications

Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

TOXGB: Teamwork Optimization Based XGBoost model for early identification of post-traumatic stress disorder

Neural Transcriptomic Analysis of Sex Differences in Autism Spectrum Disorder: Current Insights and Future Directions

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