Model Of Posttraumatic Stress Disorder Research Articles

MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans

Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e., the Trier Social Stress Test and the dexamethasone suppression test (DST), in whole blood of two independent cohorts of PTSD patients vs. non-traumatized healthy controls (HC) and, moreover, in a mouse model of PTSD and in dexamethasone-treated mice. Besides MMP9, we quantified mRNA levels of four of its regulators, i.e., interleukin (IL)-1 receptor 1 and 2 (IL1R1, IL1R2), IL-6 receptor and tumor necrosis factor receptor 1 (TNFR1) in 10 patients exposed to the DST before vs. after successful PTSD psychotherapy vs. 13 HC and, except from Il6r, also in different brain regions of the PTSD mouse model. We are the first to show that blood MMP9 mRNA concentrations were elevated after acute dexamethasone in PTSD patients, improved upon partial remission of PTSD and were, furthermore, also elevated, together with its regulator Tnfr1, in the prefrontal cortex of PTSD-like mice. In contrast, blood TNFR1 and IL1R2 were markedly underexpressed in PTSD patients. In conclusion, we found translational evidence supporting that, I, TNFR1 and MMP9 mRNA expression might be involved in PTSD pathobiology, II, might constitute potential diagnostic blood biomarkers for PTSD and, importantly, III, post-dexamethasone blood MMP9 hyperexpression, which speculatively results from post-dexamethasone underexpression of IL1R2, might serve also as potential treatment monitoring biomarker for PTSD.

Dysregulation of miR-15a-5p, miR-497a-5p and miR-511-5p Is Associated with Modulation of BDNF and FKBP5 in Brain Areas of PTSD-Related Susceptible and Resilient Mice.

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder occurring in susceptible individuals following a traumatic event. Understanding the mechanisms subserving trauma susceptibility/resilience is essential to develop new effective treatments. Increasing evidence suggests that non-coding RNAs, such as microRNAs (miRNAs), may play a prominent role in mediating trauma susceptibility/resilience. In this study, we evaluated the transcriptional expression of two key PTSD-related genes (FKBP5 and BDNF) and the relative targeting miRNAs (miR-15a-5p, miR-497a-5p, miR-511-5p, let-7d-5p) in brain areas of PTSD-related susceptible and resilient mice identified through our recently developed mouse model of PTSD (arousal-based individual screening (AIS) model). We observed lower transcript levels of miR-15a-5p, miR-497a-5p, and miR-511a-5p in the hippocampus and hypothalamus of susceptible mice compared to resilient mice, suggesting that the expression of these miRNAs could discriminate the two different phenotypes of stress-exposed mice. These miRNA variations could contribute, individually or synergically, to the inversely correlated transcript levels of FKBP5 and BDNF. Conversely, in the medial prefrontal cortex, downregulation of miR-15a-5p, miR-511-5p, and let-7d-5p was observed both in susceptible and resilient mice, and not accompanied by changes in their mRNA targets. Furthermore, miRNA expression in the different brain areas correlated to stress-induced behavioral scores (arousal score, avoidance-like score, social memory score and PTSD-like score), suggesting a linear connection between miRNA-based epigenetic modulation and stress-induced phenotypes. Pathway analysis of a miRNA network showed a statistically significant enrichment of molecular processes related to PTSD and stress. In conclusion, our results indicate that PTSD susceptibility/resilience might be shaped by brain-area-dependent modulation of miRNAs targeting FKBP5, BDNF, and other stress-related genes.

102 Single-Prolonged Stress as a Model of PTSD in Mice: Effects on Sleep and Anxiety

Abstract Introduction Sleep problems are common in humans with post-traumatic stress disorder (PTSD). Rapid eye movement (REM) sleep is involved in processing emotional memories; it is often disrupted in those with PTSD, and may be related to increased anxiety. Single prolonged stress (SPS) is a protocol used to model PTSD in rats, however little is known about how this model impacts sleep in mice. Prior research suggests SPS produces short term disturbances in REM sleep and increases in anxiety-like behavior, but further validation of this model is needed to understand how SPS impacts sleep and anxiety-like behaviors in mice specifically, as they have greater potential for transgenic manipulation Methods C57BL6/J mice underwent a SPS protocol in which they were tube-restrained for 2 hours, followed by a 15 minute forced swim in a group, ether exposure until loss of consciousness, and 10 days of social isolation. Following SPS, mice were tested for anxiety-like behavior in a light-dark box and sleep was measured from surgically implanted EEG and EMG leads. Time spent in wake, REM sleep, and non-REM sleep was quantified for 24 continuous hours in SPS and Control mice. Results There were no significant effects of SPS on the amount of time spent in any vigilance state, or in sleep-wake transitions. However, SPS-exposed mice showed significantly more anxiety-like behavior. EEG power spectra were analyzed in relevant frequency bands during each sleep state, and exploratory analyses were conducted Conclusion Minimal effects on sleep macroarchitecture were seen in mice 10 days after SPS. It is possible that sleep disturbances seen immediately after trauma exposure (such as in prior studies in rats) may have diminished over time. Further studies will need to include additional timepoints and analysis of sleep microarchitecture following SPS, and in other mouse models of PTSD, in order to more comprehensively examine changes in sleep. Support (if any) VA CDA #IK2 BX002712, Portland VA Research Foundation, Medical Research Foundation

Traumatic memory: Molecular and cellular mechanisms of post‐traumatic stress disorder

The mechanisms of post-traumatic stress disorder (PTSD) have attracted increasing attention in recent years. However, despite the great success in the study of PTSD at the behavioral, psychological and physiological level in humans, as well as large number animal models of PTSD, the phenomenon of PTSD remains largely incomprehensible in theoretical terms. The aim of this project is to establish the neural basis for the pathological stability of traumatic memory that formed when encountering a stressful situation leading to the development of PTSD and to study the differences between the mechanisms of normal and traumatic memory formation at the neural level. First, we subjected mice to single traumatic experience and studied the dependence of PTSD development on protein synthesis during the consolidation and reconsolidation of traumatic memory. Mice injected with protein synthesis inhibitor cycloheximide (90 mg/kg, i.p.) 30 min before PTSD induction retained contextual associative memory but did not show a pronounced contextual fear. The results of elevated plus maze test suggests that the protein synthesis inhibition during the consolidation of traumatic memory can not only prevent the development of PTSD, but also disrupt the natural defensive behavior of animals, making them less anxious than control mice who had no previous negative experience. Than we showed that protein synthesis inhibition during the reconsolidation of traumatic memory almost completely abolish non-specific symptoms of trauma in mice, such as increased sensitization, fear generalization and anxiety. At the same time, however, cycloheximide injection during reminder did not affect the associative fear memory. These results show a dissociation between associative and nonassociative consequences of a traumatic experience in terms of their sensitivity to impairment during memory retrieval. We also studied the dependence of PTSD development on de novo methylation processes. Methyltransferase inhibitors 5-AZA and RG108 injection (0.5 mg/kg, i.p.) 30 min before traumatic episode reduced PTSD symptoms in mice: it decreased the level of conditioned fear and affected the level of behavioral sensitization and anxiety, but not the generalization. The inhibition of methylation processes during the reconsolidation of traumatic memory did not affect the symptoms of PTSD according to our data. We analyzed the c-Fos activity of the brain in the formation of normal contextual fear memory (FC) and traumatic memory in order to answer the second question of this project. The formation of traumatic memory was accompanied by activation of a pattern of brain areas similar to that activated during formation of FC memory. However, in PTSD the activity of amygdala, prelimbic cortex and dentate gyrus was considerably more pronounced. These results show important differences between normal and traumatic forms of memory at the time of their formation. In addition we hypothesize that increased activation of the amygdala and prefrontal cortex in PTSD may be associated with pathological persistence of traumatic memory.

Risk factors for post-traumatic stress disorder in acute trauma patients: A protocol for systematic review and meta-analysis.

Background:Post-traumatic stress disorder (PTSD) is one of the most commonly reported mental health consequences, followed by disasters and traumatic events, either natural or man-made. At present, there are no unified results for the prevalence rate of PTSD in patients suffering from acute trauma and related influencing factors. Therefore, the purpose of this study is to systematically evaluate the existing literatures, thus obtaining a comprehensive estimation of the combined prevalence rate of PTSD and related factors in trauma patients, so as to provide evidence support for clinical disease prediction models and intervention strategies.Methods:Published articles will be retrieved from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Research reports will be searched in March 2021. STATA 14.0 software will be applied for data analysis. Mantel–Haenszel fixed effect model or DerSimonian–Laird random effect model will be selected to estimate the pooled prevalence of PTSD in patients with acute trauma and associated factors.Results:We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.Conclusions:The results of this analysis can be used to establish a risk prediction model of PTSD in patients experiencing acute trauma, so as to provide intervention strategies.OSF Registration Number:DOI 10.17605/OSF.IO/Z275U.

Testing Glucocorticoid Mediated Differential Gene Expression in IPSC Derived Neural Cultures as a Model for PTSD

Posttraumatic Stress Disorder (PTSD) is a common complex psychiatric disorder affecting 6.1% of Americans, and no efficacious cellular models exists for studying the disease. Utilizing a transcriptomic imputation approach with the latest GWAS and TWAS analyses of PTSD, our group has recently predicted DLPFC gene expression, and its constituent cell types, in the disease's pathology.

Repeated Social Defeat Stress Leads to Pro-Inflammatory T-Lymphocytes via Dendritic Cell Priming

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that increases the risk of comorbid inflammatory diseases by >3 fold, but the mechanisms remain elusive. We previously reported elevated levels of mitochondrial superoxide and inflammatory cytokines in T-lymphocytes from mice undergoing repeated social defeat stress (RSDS; a preclinical model of PTSD). These findings suggested T-lymphocyte activation, but the mechanisms underlying this activation remain elusive. Therefore, we hypothesized that RSDS stimulates antigen presenting cells (i.e., dendritic cells), which in turn potentiates T-lymphocyte activation and pro-inflammatory differentiation.

Relational Spirituality and Transgenerational Obligations: The Role of Family in Lay Explanatory Models of Post-traumatic Stress Disorder in Male Cameroonian Asylum Seekers and Undocumented Migrants in Europe.

Context: Diasporic Cameroonians are increasingly leading a transnational life in which family members are sustained through networks of relations and obligations. However, before arriving in Europe, the vast majority of African migrants who take the Mediterranean route are exposed to trauma and hardship. Moreover, the joint occurrence of forced displacement, trauma, and extended separation from families has a significant impact on mental health.Objectives: This study explores the role of culture-specific conceptualizations of family structures and transnationalism in explanatory models of post-traumatic stress disorder (PTSD) among male Cameroonian asylum-seekers and undocumented migrants in Europe.Methods: An in-depth study of two samples of Cameroonian migrants with a precarious residency status in Europe was conducted. Focus group discussions and interviews were carried out with asylum seekers in Germany (n = 8) and undocumented migrants and failed asylum seekers in France (n = 9). The verbatim transcripts of these interviews served as the data for interpretative phenomenological analyses.Results, Analysis, and Discussion: Family was conceptualized in religious and spiritual terms, and relational spirituality appeared to be a crucial element of family cohesion. Explanatory models of PTSD were mainly based on an intersection of family and spirituality. The disrespect of transgenerational, traditional, and spiritual obligations toward parents and ancestral spirits represented a crucial causal attribution for post-traumatic symptoms.Conclusions: Conceptualizations of post-traumatic stress were based on a collective family and spiritual level instead of an individualized illness-centered perception. The Western psychological and psychiatric perspective on post-traumatic stress might conflict with traditional, religious, and spiritual practices in the context of family conceptualizations of Cameroonian forced migrants with a precarious residency status.

Increased Oxidative Stress in the Prefrontal Cortex as a Shared Feature of Depressive- and PTSD-Like Syndromes: Effects of a Standardized Herbal Antioxidant.

Major depression (MD) and posttraumatic stress disorder (PTSD) share common brain mechanisms and treatment strategies. Nowadays, the dramatically developing COVID-19 situation unavoidably results in stress, psychological trauma, and high incidence of MD and PTSD. Hence, the importance of the development of new treatments for these disorders cannot be overstated. Herbal medicine appears to be an effective and safe treatment with fewer side effects than classic pharmaca and that is affordable in low-income countries. Currently, oxidative stress and neuroinflammation attract increasing attention as important mechanisms of MD and PTSD. We investigated the effects of a standardized herbal cocktail (SHC), an extract of clove, bell pepper, basil, pomegranate, nettle, and other plants, that was designed as an antioxidant treatment in mouse models of MD and PTSD. In the MD model of “emotional” ultrasound stress (US), mice were subjected to ultrasound frequencies of 16–20 kHz, mimicking rodent sounds of anxiety/despair and “neutral” frequencies of 25–45 kHz, for three weeks and concomitantly treated with SHC. US-exposed mice showed elevated concentrations of oxidative stress markers malondialdehyde and protein carbonyl, increased gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and other molecular changes in the prefrontal cortex as well as weight loss, helplessness, anxiety-like behavior, and neophobia that were ameliorated by the SHC treatment. In the PTSD model of the modified forced swim test (modFST), in which a 2-day swim is followed by an additional swim on day 5, mice were pretreated with SHC for 16 days. Increases in the floating behavior and oxidative stress markers malondialdehyde and protein carbonyl in the prefrontal cortex of modFST-mice were prevented by the administration of SHC. Chromatography mass spectrometry revealed bioactive constituents of SHC, including D-ribofuranose, beta-D-lactose, malic, glyceric, and citric acids that can modulate oxidative stress, immunity, and gut and microbiome functions and, thus, are likely to be active antistress elements underlying the beneficial effects of SHC. Significant correlations of malondialdehyde concentration in the prefrontal cortex with altered measures of behavioral despair and anxiety-like behavior suggest that the accumulation of oxidative stress markers are a common biological feature of MD and PTSD that can be equally effectively targeted therapeutically with antioxidant therapy, such as the SHC investigated here.

Photobiomodulation prevents PTSD-like memory impairments in rats

A precise fear memory encoding a traumatic event enables an individual to avoid danger and identify safety. An impaired fear memory (contextual amnesia), however, puts the individual at risk of developing posttraumatic stress disorder (PTSD) due to the inability to identify a safe context when encountering trauma-associated cues later in life. Although it is gaining attention that contextual amnesia is a critical etiologic factor for PTSD, there is no treatment currently available that can reverse contextual amnesia, and whether such treatment can prevent the development of PTSD is unknown. Here, we report that (I) a single dose of transcranial photobiomodulation (PBM) applied immediately after tone fear conditioning can reverse contextual amnesia. PBM treatment preserved an appropriately high level of contextual fear memory in rats revisiting the “dangerous” context, while control rats displayed memory impairment. (II) A single dose of PBM applied after memory recall can reduce contextual fear during both contextual and cued memory testing. (III) In a model of complex PTSD with repeated trauma, rats given early PBM interventions efficiently discriminated safety from danger during cued memory testing and, importantly, these rats did not develop PTSD-like symptoms and comorbidities. (IV) Finally, we report that fear extinction was facilitated when PBM was applied in the early intervention window of memory consolidation. Our results demonstrate that PBM treatment applied immediately after a traumatic event or its memory recall can protect contextual fear memory and prevent the development of PTSD-like psychopathological fear in rats.

Efficacy and Underlying Mechanism of Acupuncture in the Treatment of Posttraumatic Stress Disorder: A Systematic Review of Animal Studies.

Acupuncture is a nonpharmacological intervention that can be useful in the clinical management of posttraumatic stress disorder (PTSD), especially in situations with a lack of medical resources, including large-scale PTSD events such as disasters. Some clinical studies have reported the clinical effect of acupuncture in improving PTSD symptoms, but the underlying therapeutic mechanism has yet to be explored. Therefore, this review summarized the underlying therapeutic mechanisms of acupuncture in animal PTSD models. A comprehensive search was conducted in 14 electronic databases, and two independent researchers performed study selection, data extraction, and the methodological quality assessment. Twenty-four relevant studies were included in this review and summarized according to the proposed main mechanisms. In behavioral evaluation, acupuncture, including manual acupuncture and electro-acupuncture, reduced anxiety and fear responses and weakened fear conditioning, improved sleep architecture, reduced depressive symptoms, and alleviated disturbance of spatial learning and memory of PTSD animal models. The therapeutic mechanisms of acupuncture proposed in the included studies could be classified into two categories: (1) regulation of stress responses in the neuroendocrine system and (2) promotion of neuroprotection, neurogenesis, and synaptic plasticity in several brain areas. However, the methodological quality of the included animal studies was not high enough to produce robust evidence. In addition, mechanistic studies on specific aspects of acupuncture that may affect PTSD, including expectancy effects, in human PTSD subjects are also needed.

The administration of sertraline plus naltrexone reduces ethanol consumption and motivation in a long-lasting animal model of post-traumatic stress disorder

This study was aimed to evaluate the effects of sertraline (STR) and/or naltrexone (NTX) on ethanol consumption and motivation in an animal model of post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD).Male C57BL/6J mice were submitted to an intermittent and progressively increasing stressful stimuli simulating PTSD behavioural features. Behavioural alterations were explored by the fear conditioning (FC), novelty suppressed feeding test (NSFT) and acoustic startle response (ASR) paradigms. Afterwards, mice were evaluated in the voluntary ethanol consumption (VC) and the oral ethanol self-administration (OEA) paradigms. The effects of STR (10 mg/kg) and/or NTX (0.7 mg/kg) on ethanol consumption and motivation were analysed in the OEA. Furthermore, relative gene expression analyses of tyrosine hydroxylase (Th), mu-opioid receptor (Oprm1) and 5-hydroxitryptamine transporter (Slc6a4) were performed in the ventral tegmental area (VTA), nucleus accumbens (NAcc) and dorsal raphe nucleus (DR), respectively.PTSD-like mice presented increased fear-related memory, anxiety-like behaviours, and startle response, as well as enhanced ethanol consumption and motivation in the VC and OEA paradigms. Interestingly, STR plus NTX combination significantly reduced ethanol intake and motivation in the OEA. Gene expression analyses revealed reduced Th and Oprm1 whereas Slc6a4 gene expression increased in PTSD-like mice. STR and/or NTX modulated Th and Slc6a4 gene expression changes in PTSD-like mice. Furthermore, NTX increased Oprm1 gene expression revealing a synergistic action when combined with STR.These results provide evidence about the efficacy of the STR plus NTX to attenuate ethanol reinforcement and motivation in an animal model of PTSD and AUD dual pathology.

Vagus nerve stimulation promotes extinction generalization across sensory modalities

Traumatic experiences involve complex sensory information, and individuals with trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD), can exhibit abnormal fear to numerous different stimuli that remind them of the trauma. Vagus nerve stimulation (VNS) enhances extinction of auditory fear conditioning in rat models for PTSD. We recently found that VNS-paired extinction can also promote extinction generalization across different auditory cues. Here we tested whether VNS can enhance extinction of olfactory fear and promote extinction generalization across auditory and olfactory sensory modalities. Male Sprague Dawley rats were implanted with a stimulating cuff on the cervical vagus nerve. Rats then received two days of fear conditioning where olfactory (amyl acetate odor) and auditory (9 kHz tones) stimuli were concomitantly paired with footshock. Twenty-four hours later, rats were given three days of sham or VNS-paired extinction (5 stimulations, 30-sec trains at 0.4 mA) overlapping with presentation of either the olfactory or the auditory stimulus. Two days later, rats were given an extinction retention test where avoidance of the olfactory stimulus or freezing to the auditory stimulus were measured. VNS-paired with exposure to the olfactory stimulus during extinction reduced avoidance of the odor in the retention test. VNS-paired with exposure to the auditory stimulus during extinction also decreased avoidance of the olfactory cue, and VNS paired with exposure to the olfactory stimulus during extinction reduced freezing when the auditory stimulus was presented in the retention test. These results indicate that VNS enhances extinction of olfactory fear and promotes extinction generalization across different sensory modalities. Extinction generalization induced by VNS may therefore improve outcomes of exposure-based therapies.

What's in a name? Comparing alternative conceptualizations of posttraumatic stress disorder among preadolescent children following the Boston Marathon bombing and manhunt

ABSTRACT Background and Objectives New diagnostic criteria for posttraumatic stress disorder (PTSD) were introduced by DSM-5 and ICD-11. It remains unclear how well these new definitions of PTSD capture the posttrauma responses of children, particularly when using parent report. This study compared different conceptual models of PTSD in children following the Boston Marathon bombing and manhunt. Design and Methods Parents/caretakers (N = 254) reported on PTSD symptoms of their children (ages 4–11) following the Boston Marathon bombing and manhunt. Algorithms compared criteria from ICD-11, DSM-IV, and DSM-5 (specifically the “Preschool” criteria). Results DSM-5 Preschool criteria identified twice as many children as ICD-11, and over four times as many as DSM-IV. DSM-5 Preschool criteria identified all cases detected by ICD-11 and DSM-IV. Across models, all identified cases had greater trauma exposure than non-identified children. DSM-5 Preschool and ICD-11 (but not DSM-IV) cases had greater clinical decline than non-identified children. The Avoidance cluster showed the most variability in identifying cases. Conclusions Newer models of PTSD are likely to identify more children than DSM-IV, mostly related to changes in the Avoidance criteria. The DSM-5 Preschool definition is the most inclusive model. ICD-11 may provide a balance between inclusivity and stringency in detecting childhood PTSD.

MiR-132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF

Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF and is regulated by miR-132-3p. In the present study, we explored the possible molecular mechanism of miR-132, focusing on the involvement of MeCP2 and BDNF in the formation of anxiety-like symptoms of PTSD. Single prolonged stress (SPS) was used to establish a model of PTSD in adult rats and the anxiety-like behavior was tested by the elevated plus-maze (EPM). The level of miR-132 in the prefrontal cortex (PFC) was increased and intraventricular injection of anti-miR-132 could significantly improve the anxiety-like behavior of rats exposed to SPS through MeCP2 and the subsequent upregulation of BDNF levels. Then tropomyosin-related kinase B (TrkB) and downstream signals, including MAP kinase ERK1/2 and phosphoinositol 3-kinase (PI3K)/Akt pathways, were activated by BDNF upregulation, and might participate in regulating dendritic complexity and the expression of postsynaptic density-95 (PSD95) and synapsin I in the PFC of SPS rats. Furthermore, we found that the apoptosis of cells in PFC induced by SPS procedure could be alleviated by miR-132 inhibition. Our results suggest that miR-132 might be involved in the formation of anxiety-like symptoms of adult rat PTSD models by targeting MeCP2, and this effect is related to BDNF/TrkB and its downstream ERK and Akt signaling pathways.

Racial and ethnic disparities in posttraumatic psychopathology among postpartum women

People of color in the United States disproportionately bear the burden of trauma and posttraumatic stress disorder (PTSD). Pregnant women of color are at particular risk, as perinatal PTSD is associated with adverse maternal and child health. However, PTSD is a heterogeneous disorder comprising discrete symptom dimensions. Adopting a dimensional understanding of PTSD could aid in identifying women at-risk for the consequences of posttraumatic psychopathology and guide treatment selection. In a large sample of Latina, Black, and non-Hispanic White postpartum women in the United States (N = 1663), we examined racial and ethnic differences in the factors of the dysphoric arousal model—a leading dimensional model of PTSD. This model is characterized by five symptom dimensions: re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal. Past-year trauma in this sample was common, afflicting nearly 70% of women. In unadjusted models, women of color exhibited more severe PTSD symptom levels across dimensions except for dysphoric arousal, with Black mothers particularly affected. In models adjusted for age, education, and poverty, Black women continued to report elevated symptoms of avoidance and, relative to Latina mothers, re-experiencing symptoms. In contrast, White women reported more dysphoric arousal symptoms relative to women of color. Illuminating differential patterns of symptom dimensions across racial and ethnic groups is critical to PTSD assessment and treatment and may shed light on disparities. Perinatal healthcare may be an important opportunity for posttraumatic symptom screening, and greater understanding of racial and ethnic variation in posttraumatic symptom dimensions can guide targeted intervention selection for perinatal women.

Anti-PTSD Effects of Hypidone Hydrochloride (YL-0919): A Novel Combined Selective 5-HT Reuptake Inhibitor/5-HT1A Receptor Partial Agonist/5-HT6 Receptor Full Agonist.

Posttraumatic stress disorder (PTSD) is a debilitating trauma and stressor-related disorder that has become a major neuropsychiatric problem, leading to substantial disruptions in individual health and societal costs. Our previous studies have demonstrated that hypidone hydrochloride (YL-0919), a novel combined selective 5-HT reuptake inhibitor/5-HT1A receptor partial agonist/5-HT6 receptor full agonist, exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 exerts anti-PTSD effects and its underlying mechanisms are still unclear. In the present study, we showed that repeated treatment with YL-0919 caused significant suppression of contextual fear, enhanced anxiety and cognitive dysfunction induced by the time-dependent sensitization (TDS) procedure in rats and by inescapable electric foot-shock in a mouse model of PTSD. Furthermore, we found that repeated treatment with YL-0919 significantly reversed the accompanying decreased expression of the brain-derived neurotrophic factor (BDNF) and the synaptic proteins (synapsin1 and GluA1), and ameliorated the neuroplasticity disruption in the prefrontal cortex (PFC), including the dendritic complexity and spine density of pyramidal neurons. Taken together, the current study indicated that YL-0919 exerts clear anti-PTSD effects, which might be partially mediated by ameliorating the structural neuroplasticity by increasing the expression of BDNF and the formation of synaptic proteins in the PFC.

Behavioral profiling reveals an enhancement of dentate gyrus paired pulse inhibition in a rat model of PTSD

We recently introduced behavioral profiling as a translational approach to increase the validity of animal models of posttraumatic stress disorder (PTSD). Behavioral profiling utilizes the response of a ‘normal population’ of control animals and compares the performance of animals with a history of traumatic stress in different behavioral tests that can capture PTSD-like symptoms. Thus, affected, PTSD-like individuals can be subdivided from resilient trauma-exposed animals.While in our recent study we focused mainly on tests for activity and anxiety, we now expand the behavioral tests battery and include also fear memory and extinction tasks as well as a spatial object recognition test in our behavioral profiling approach. Utilizing underwater trauma as the traumatic event, we found that only a small subset of animals exposed to underwater trauma showed lasting increases in anxiety-like behavior and heightened emotional memory formation. Adding juvenile stress as a model for childhood adversity increased the prevalence of such affected animals and furthermore and induced additional cognitive deficits in a subgroup of such emotionally affected individuals. In addition, multiple affected individual rats displayed increased local circuit activity in the dorsal dentate gyrus, as measured in vivo with paired pulse protocols in anesthetized animals.Together, our findings highlight behavioral profiling, refined by including multiple behavioral tests, as a valid tool to identify PTSD-like vs. resilient individual animals and further suggest that enhanced local inhibition in specific circuits of the dorsal dentate gyrus may be associated with the observed symptoms.

Childhood maltreatment is associated with distrust and negatively biased emotion processing

BackgroundCognitive models of post-traumatic stress disorder (PTSD) propose that trauma entails cognitive alterations of increased distrust and perceived threat from others. We tested whether these predictions also hold in individuals with varying levels of childhood maltreatment (CM), which is much more prevalent than traumatic events as required for a PTSD diagnosis. We hypothesized that higher levels of CM would entail greater distrust and perceived threat, and that distrust would be more change-resistant in participants with more CM.MethodsThe study was pre-registered; the pre-registration protocol, data, and code are available at https://osf.io/pufy2/. We recruited 549 participants (M age = 29.2, 74.5% women) for an online study via websites related to CM, Borderline Personality Disorder, and via snowball method on social media. Participants self-reported their level of CM on the childhood trauma questionnaire (CTQ). Next, they played two rounds of a hypothetical distrust game, indicating the perceived trustworthiness of avatars by way of estimating expected monetary deductions from them (i.e. higher amounts indicating greater distrust). After the first round, we provided participants with the feedback that very little money was taken from them. We expected those with more CM to be less responsive to the positive feedback and to adapt their estimates less in the subsequent round. Following the distrust game, participants completed an emotion rating task in which they rated the emotional expressions of 60 faces on a scale from ‘very negative’ to ‘very positive’. We included angry, fearful, and happy facial expressions, and expected individuals with higher CM levels to provide more negative ratings. We conducted linear mixed effects models with random intercepts for raters and stimuli (crossed), and modelled random slopes for all within-person predictors.ResultsAs hypothesized, higher levels of CM were associated with higher levels of distrust and a weaker decrease in distrust following positive feedback. Further supporting our hypotheses, individuals with higher levels of CM showed more negatively shifted emotion ratings.ConclusionsIncreased distrust and perceived interpersonal threat following trauma, as proposed in cognitive models of PTSD, likely also apply to individuals with CM, following a dose-response relationship. We discuss clinical implications of considering any level of CM as a potentially relevant treatment-factor, even when a trauma-related disorder is not the main diagnosis, and propose future research avenues.

Investigating centrality in PTSD symptoms across diagnostic systems using network analysis*

ABSTRACT Background: The posttraumatic stress disorder (PTSD) diagnosis has been widely debated since it was introduced into the diagnostic nomenclature four decades ago. Recently, the debate has focused on consequences of having two different descriptions of PTSD: 20 symptoms belonging to four symptom clusters in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), and three symptoms clusters in the 11th edition of the International Classification of Diseases (ICD-11) most often operationalized by six symptoms in the International Trauma Questionnaire (ITQ) (2017) and Hansen, Hyland, Armour, Shevlin, & Elklit (2015). Research has provided support for both models of PTSD, but at the same time indicates differences in estimated prevalence rates of PTSD (Hansen et al., 2015, 2017). A growing body of research has modelled PTSD both theoretically and statistically as a network of interacting symptoms (Birkeland, Greene, & Spiller, 2020), yet it remains more unclear how the two diagnostic systems perform regarding which symptoms are more central/interconnected. Objectives and methods: We estimated two 23-item Gaussian Graphical Models to investigate whether ICD-11 or DSM-5 PTSD symptoms are more central in two trauma-exposed samples: a community sample (N = 2,367) and a military veteran sample (N = 657). PTSD DSM-5 was measured with the PTSD checklist-5 (PCL-5) and the PTSD ICD-11 was measure by the ITQ PTSD subscale. Results: Five of the six most central symptoms estimated via the expected influence centrality metric across the two samples were identical and represented symptoms from both diagnostic systems operationalized by the PCL-5 and the ITQ. Conclusions: The results of the present study underline that symptoms from both diagnostic systems hold central positions. The implications of the results are discussed from the perspectives of an indexical (i.e. the diagnostic systems reflect both shared and different aspects of PTSD) and a constitutive view (i.e., the diagnostic systems represent different disorders and the results cannot be reconciled per se) of mental health diagnoses (Kendler, 2017).