Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder

Nisar, Sabah; Bhat, Ajaz A.; Hashem, Sheema; Syed, Najeeb; Yadav, Santosh K.; Uddin, Shahab; Fakhro, Khalid; Bagga, Puneet; Thompson, Paul M.; Reddy, Ravinder; Frenneaux, Michael; Haris, Mohammad

doi:10.3390/ijms21124503

Cited by 37 publications

(26 citation statements)

References 98 publications

(110 reference statements)

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“…Posttraumatic stress disorder (PTSD) is a complex condition that develops after exposure to a serious and often life-threatening event (Nisar et al, 2020). Core symptoms include avoidance, hyperarousal, reexperiencing, and negative alterations in mood and cognition.…”

Section: Posttraumatic Stress Disordermentioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen

Tubi

Bright

et al. 2021

Human Brain Mapping

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Sex is a biological variable that contributes to individual variability in brain structure and behavior. Neuroimaging studies of population-based samples have identified normative differences in brain structure between males and females, many of which are exacerbated in psychiatric and neurological conditions. Still, sex differences in MRI outcomes are understudied, particularly in clinical samples with known sex differences in disease risk, prevalence, and expression of clinical symptoms. Here we review the existing literature on sex differences in adult brain structure in normative samples and in 14 distinct psychiatric and neurological disorders. We discuss commonalities and sources of variance in study designs, analysis procedures, disease subtype effects, and the impact of these factors on MRI interpretation. Lastly, we identify key problems in the neuroimaging literature on sex differences and offer potential recommendations to address current barriers and optimize rigor and reproducibility. In particular, we emphasize the importance of large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses consortium, the UK Biobank, Human Connectome Project, and others to provide unprecedented power to evaluate sex-specific phenotypes in major brain diseases.

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Section: Posttraumatic Stress Disordermentioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen

Tubi

Bright

et al. 2021

Human Brain Mapping

View full text Add to dashboard Cite

show abstract

“…Post-traumatic stress disorder (PTSD) is a complex condition that develops after exposure to a serious and often life-threatening event [Nisar et al, 2020]. The lifetime prevalence of PTSD is significantly higher for females (2.6%) than males (1.0%) cross-nationally (N=71,083) [Koenen et al, 2017], with around twice the prevalence for females (lifetime=6.1%, 12-month=6.1%) than males (lifetime=4.1%, 12-month=3.2%) in the US [Goldstein et al 2016], despite experiencing similar numbers of traumatic events [Lehavot et al, 2018].…”

Section: Post-traumatic Stress Disordermentioning

confidence: 99%

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Salminen¹,

Tubi²,

Bright³

et al. 2020

Preprint

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Sex differences are found in the incidence and expression of psychiatric and neurodegenerative conditions, and many studies suggest these differences are influenced by innate biological differences between males and females and risk factors that interact with these differences. However, few studies have used neuroimaging to examine brain signatures of disease separately by sex, and many studies of sex differences have been based on small samples and their findings have not been replicated in larger cohorts. Large-scale neuroimaging initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analyses (ENIGMA) consortium, the UK Biobank, Human Connectome Project, and others offer an unprecedented source of power to address important questions about the role of sex as a risk or protective factor for suboptimal brain health, as well as sex-specific neuroimaging phenotypes in brain-related illnesses. Here we review the existing neuroimaging literature on sex differences in the human brain in healthy adults and those with the most common and debilitating psychiatric and age-related neurodegenerative conditions. Finally, we discuss key gaps in this literature and opportunities of large-scale collaborative efforts to identify, characterize, and explain how biological sex influences the humanbrain in health and disease.

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“…Although the understanding of the molecular mechanism of PTSD has made great progress over the years, the exact pathogenesis is still unclear. MRI examination of PTSD patients showed that the hippocampus volume decreased (Milani et al 2017;Moyer 2016;Nisar et al 2020), animal experiments also found that the hippocampus of PTSD was closely related to the memory loss after a long delay (Joshi et al 2020; Shan et al 2020). The above results show that the abnormality of hippocampus were the important pathogenesis of PTSD.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuron Apoptosis in SPS Rats

han¹,

Xu²,

Shi

2021

Preprint

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Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also one of the important reasons of memory disorder in PTSD patients. The endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α(ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. The PTSD rat model was constructed by the single-prolonged stress (SPS) method. The experiment was divided into two parts: (1) Control group, SPS 1d group, SPS 7d group, SPS 14d group. (2) Control group, SPS 7d group, SPS 7d+AEBSF group, control+AEBSF group. 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor. The expression of ATF6α, glucose regulated protein (GRP78), S1P, S2, C/EBP homologous protein (CHOP), caspase-12 protein and mRNA in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. The apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α, GRP78 increased gradually in SPS 1d group and SPS 7d group, but decreased in SPS 14d group(P<0.01). In experiment 2, compared with the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly increased in SPS 7d group(P<0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly decreased after AEBSF pretreatment(P<0.01). SPS induces apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.

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Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder

Cited by 37 publications

References 98 publications

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

Molecular Mechanism of ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuron Apoptosis in SPS Rats

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