Activity In Posttraumatic Stress Disorder Research Articles

The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees

BackgroundExposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AimThe aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. MethodsAdult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. Results115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. ConclusionsThis study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. EthicsThe study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder.

Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11–16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls. Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which the profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle analysis seems a promising tool to detect aberrant spindling in psychiatric disorders.

Sex differences in post-traumatic stress disorder risk: autonomic control and inflammation.

Over 7 million U.S. adults and about 20% of the military population have post-traumatic stress disorder (PTSD), a debilitating condition that is independently linked to a significantly greater risk of developing cardiovascular disease (CVD). Women have twice the probability of developing PTSD after experiencing a traumatic event compared to men. Existing literatures have reported higher inflammation and autonomic dysfunction including impaired baroreflex sensitivity, increased sympathetic reactivity and decreased parasympathetic activity in PTSD. However, most of these findings stem from studies conducted predominantly in males. We attempt in this narrative review to summarize the mixed literature available on sex differences in autonomic dysfunction and inflammation in PTSD, at rest and in response to stress in PTSD. This review reveals that there is a paucity of research exploring autonomic function in females with PTSD. Recent studies have included female participants without probing for sex differences. A small number of studies have been conducted exclusively in women. Available data suggest that sympathetic nervous system output tends to be heightened, while parasympathetic activity and arterial baroreflex sensitivity appear more blunted in females with PTSD. Although few studies have investigated sex differences in inflammation in PTSD, data within females suggest chronic increases in inflammation with PTSD. This autonomic dysregulation and inflammation have also been described in males with PTSD. In sum, given the inherent biological differences in CVD clinical presentation and characteristics between men and women, human and animal studies aiming at elucidating sex differences in the pathophysiology of PTSD are needed.

Autonomic dysfunction in posttraumatic stress disorder indexed by heart rate variability: a meta-analysis.

Changes in autonomic nervous system (ANS) function have been observed in a variety of psychological disorders, including posttraumatic stress disorder (PTSD). Analysis of heart rate variability (HRV) provides insight into the functioning of the ANS. Previous research on PTSD found lower HRV in PTSD patients compared to controls, indicating altered sympathetic and parasympathetic activity, but findings are inconsistent. The purpose of this meta-analysis was to examine differences in HRV indices between individuals with PTSD and healthy controls at baseline and during stress. The included primary studies present an aggregate of studies analyzing different HRV indices. Examined HRV indices were standard deviation of the normalized NN-intervals (SDNN), root mean square of successive differences (RMSSD), low-frequency (LF) and high-frequency (HF) spectral components, LF/HF ratio, and heart rate (HR). Moderating effects of study design, HRV and PTSD assessment, and sample characteristics were examined via subgroup-analyses and meta-regressions. Random-effects meta-analyses for HRV parameters at rest revealed significant group differences for RMSSD and HF-HRV, suggesting lower parasympathetic activity in PTSD. The aggregated effect size for SDNN was medium, suggesting diminished total variability in PTSD. A small effect was found for LF-HRV. A higher LF/HF ratio was found in the PTSD sample as compared to controls. Individuals with PTSD showed significantly higher HR. During stress, individuals with PTSD showed higher HR and lower HF-HRV, both indicated by small effect sizes. Findings suggest that PTSD is associated with ANS dysfunction.

PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies

Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals—with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology.

The Effects of Traumatic Experience on the Behavior, c‐Fos Expression and Functional Connections in the Mouse Brain Resting State Networks

It is known that the brains of animals and humans is active at resting state. In this paper we investigate how past experience affects characteristics of such resting state networks in animals. To do this we subjected mice to single traumatic experience that induced posttraumatic stress disorder (PTSD) and then analyzed activity of their brain (including cortex; hippocampus; amygdala; basal ganglia; thalamus; hypothalamus and midbrain) by c‐Fos cellular mapping during traumatic memory retrieval and at rest in comparison with non‐stressed animals.PTSD development led to global changes in brain activity: number of c‐Fos‐active neurons was significantly increased in different areas during traumatic memory retrieval. Similarly, at rest PTSD animals showed increased activity in 11 brain regions participating in fear memory.We identified resting state functional connections in PTSD and controls and compared them with model networks: random, scale‐free and small‐world. In both groups of mice clusterization exceeded random level. At the same time, these clusters did not interact well with each other: global efficiency of experimental networks was at the level of random network. Resting state networks of PTSD and control mice differed (Fig. 1): PTSD network was less clustered and longer paths linked the clusters. Induction of PTSD led to global changes in the structure of resting state networks. In naive animals, cortical regions had the most connections, whereas in PTSD thalamus, striatum and amygdala had. PTSD destroyed virtually all functional connections present in naive mice; only fully connected cluster of auditory and visual cortices remained. In addition, if in naive animals the main hubs were cingulate and retrosplenial cortices in PTSD animals paraventricular thalamic nucleus became the hub. In contrast, amygdala functional connectivity was virtually zero in naive animals, whereas in PTSD significant number of connections between amygdala, associative cortices, and striatum were observed.In addition, we have shown that PTSD induction changes spontaneous behavior, causing elevated anxiety and decreased research activity in safe conditions of home cages. Behavior in conditioned fear, EPM and sensitization tests also changed, and these changes could be disrupted by protein synthesis inhibition during traumatic experience, which also returned brain activity and structure of resting networks to normal in PTSD animals.Our findings show that stressful experiences can alter spontaneous behavior, induced and spontaneous brain activity and patterns of functional connections in resting state neuronal networks long after traumatic episode. We assume that these changes reflect replay of neuronal ensembles of the animal’s past subjective experience. This assumption was tested by disrupting the development of PTSD.Support or Funding InformationSupported by RSF 16‐15‐00300, 20‐15‐00187 and RFBR 19‐015‐00534, 20‐015‐00427.Resting state networks of naive mice (A, D) and PTSD animals (B, E), and their interception (C, F). A, B and C are for complete resting state networks, and D, E and À represents only connections of 11 brain areas that significantly change their activity in PTSD compared to naïve mice. Lines are Pearson’s correlations with R>0.5, p<0.05; green lines – naive resting state network; red lines – PTSD resting state network; blue lines – correlations that are present in naive and PTSD mice.Figure 1

Investigating the role of the amygdala orexin receptor 1 in memory acquisition and extinction in a rat model of PTSD

Understanding the mechanisms underlying memory is essential for the treatment of post-traumatic stress disorder (PTSD). Orexin, as a lateral hypothalamic (LH) neuropeptide, interferes with the stages of memory, primarily through the orexin receptor1 (Orx1R). The aim of this study was to evaluate the effects of amygdala Orx1R in the acquisition and extinction processes of PTSD modeled in animals.In three experiments, rats were divided into three groups: control (Naïve), shock (receiving a foot shock), and PTSD (experiencing Single prolonged stress (SPS) method). The first experiment aimed to evaluate LH activity in PTSD modeled rats. The second and third experiments aimed to evaluate the effects of Orx1R in the acquisition and extinction of fear memory in PTSD modeled animals. SB334867 (SB) or its solvent was microinjected into the amygdala and the rats were subjected to conditioning thereafter. In the second group, we used a single injection after conditioning. In the third group, we used three consecutive injections (one after each memory test). Some behaviors and Orx1R expression were evaluated.The freezing response was significantly longer in the PTSD group than on the control. Similarly, anxiety and sensitized fear were also intensified. CFos expression levels in LH was higher in the PTSD group. Inhibition of Orx1R in the amygdala significantly decreased memory acquisition, diminished anxiety, and decreased the sensitized fear in the SB group. Applying SB to the amygdala after each fear memory test significantly decreased freezing. Expression of Orx1R was significantly higher following fear conditioning.These results indicate a likely involvement of the orexin and amygdalar Orx1R in memory acquisition and in extinction of PTSD.

An attempt to identify reproducible high-density EEG markers of PTSD during sleep.

We examined electroencephalogram (EEG) spectral power to study abnormalities in regional brain activity in post-traumatic stress disorder (PTSD) during sleep. We aimed to identify sleep EEG markers of PTSD that were reproducible across nights and subsamples of our study population. Seventy-eight combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive nights of high-density EEG recordings in a laboratory. We performed spectral-topographical EEG analyses on data from both nights. To assess reproducibility, we used the first 47 consecutive participants (18 with PTSD) for initial discovery and the remaining 31 participants (13 with PTSD) for replication. In the discovery analysis, compared with non-PTSD participants, PTSD participants exhibited (1) reduced delta power (1-4 Hz) in the centro-parietal regions during nonrapid eye movement (NREM) sleep and (2) elevated high-frequency power, most prominent in the gamma band (30-40 Hz), in the antero-frontal regions during both NREM and rapid eye movement (REM) sleep. These findings were consistent across the two study nights, with reproducible trends in the replication analysis. We found no significant group differences in theta power (4-8 Hz) during REM sleep and sigma power (12-15 Hz) during N2 sleep. The reduced centro-parietal NREM delta power, indicating reduced sleep depth, and the elevated antero-frontal NREM and REM gamma powers, indicating heightened central arousal, are potential objective sleep markers of PTSD. If independently validated, these putative EEG markers may offer new targets for the development of sleep-specific PTSD diagnostics and interventions.

Strong correlation of novel sleep electroencephalography coherence markers with diagnosis and severity of posttraumatic stress disorder

Objective biomarkers of the presence and severity of posttraumatic stress disorder (PTSD) are elusive, yet badly needed. Electroencephalographic (EEG) coherence represents a promising approach to identifying and understanding brain biomarker activity in PTSD. Overnight polysomnography data containing EEG across sleep and wake states was collected in n = 76 Veterans with and without PTSD from a single site under IRB approval. Brain coherence markers (BCM) were calculated from EEG signals using a novel approach to produce one index for PTSD diagnosis (PTSDdx), and another index for PTSD severity (PTSDsev). PTSDdx showed strong sensitivity to the presence of PTSD in the awake state, during non-rapid eye movement (NREM) stage N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. PTSDsev showed a strong correlation with PTSD symptom severity (using the PTSD Checklist 5, or PCL5 survey) in the awake state, during N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. Thus, sleep EEG-based brain coherence markers can be utilized as an objective means for determining the presence and severity of PTSD. This portable, inexpensive, and non-invasive tool holds promise for better understanding the physiological mechanisms underlying PTSD and for tracking objective responses to treatment.

A review of hippocampal activation in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is often characterized by deficits in memory encoding and retrieval and aberrant fear and extinction learning. The hippocampus plays a critical role in memory and contextual processing and has been implicated in intrinsic functional connectivity networks involved in self-referential thought and memory-related processes. This review focuses on hippocampal activation findings during memory and fear and extinction learning tasks, as well as resting state hippocampal connectivity in individuals with PTSD. A preponderance of functional neuroimaging studies to date, using memory, fear learning, and extinction tasks, report decreased or "controls comparable" hippocampal activation in individuals with PTSD, which is usually associated with poorer performance on the task imaged. Existing evidence thus raises the possibility that greater hippocampal recruitment in PTSD participants may be required for similar performance levels. Studies of resting state functional connectivity in PTSD predominantly report reduced within-network connectivity in the default mode network (DMN), as well as greater coupling between the DMN and salience network (SN) via the hippocampus. Together, these findings suggest that deficient hippocampal activation in PTSD may be associated with poorer performance during memory, extinction recall, and fear renewal tasks. Furthermore, studies of resting state connectivity implicate the hippocampus in decreased within-network DMN connectivity and greater coupling with SN regions characteristic of PTSD.

Characteristics of pro- and anti-inflammatory cytokines alteration in PTSD patients exposed to a deadly earthquake

BackgroundMany studies have shown that the disturbance of pro-inflammatory and/or anti-inflammatory cytokines is involved in the modulation of traumatic stress and related psychiatric disorders, typically posttraumatic stress disorder (PTSD). However, the specific immune alterations associated with PTSD symptoms are still unclear. The present study compared levels of pro- and anti-inflammatory cytokines between PTSD and non-PTSD controls, and investigated the relationships of immune changes with PTSD symptomatology. MethodsIn this study, 51 earthquake-exposed PTSD patients and 136 earthquake-exposed healthy controls were recruited. We assessed trauma exposure, PTSD and depression severity, and quantified a panel of pro- inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), interferon ϒ (IFNϒ), and anti-inflammatory cytokines, including IL-4, IL-10 and IL-13 with enzyme-linked immunosorbent assays. Additionally, total pro-inflammatory cytokines score and total anti-inflammatory cytokines score were calculated to reflect the status of two balance system. ResultsBehavioral data showed that the PTSD group had greater severity of depression, as well as total symptoms and every symptom cluster in the seven-factor model of PTSD compared to the non-PTSD control group. Immune data showed that PTSD subjects had higher levels of IL-1β and TNFα, as well as total pro-inflammatory cytokine scores compared to controls, suggesting an increase of inflammatory activity in PTSD. In all subjects, the IL-1β levels were correlated with PCL scores, after controlling for covariates, including age, education, marital status and gender, trauma exposure severity and depression. LimitationsThe current study did not include a non-traumatized healthy control group, and PTSD was assessed using a self-reported measure. ConclusionsThus, by including a control group comprised entirely of earthquake-exposed individuals as means to discriminate specific alterations of cytokine levels in PTSD, these findings suggest that the increased inflammatory cytokines, especially IL-1β, may play a role in the pathophysiology of PTSD.

The Innate Alarm System and Subliminal Threat Presentation in Posttraumatic Stress Disorder: Neuroimaging of the Midbrain and Cerebellum

Background The innate alarm system, a network of interconnected midbrain, other brainstem, and thalamic structures, serves to rapidly detect stimuli in the environment prior to the onset of conscious awareness. This system is sensitive to threatening stimuli and has evolved to process these stimuli subliminally for hastened responding. Despite the conscious unawareness, the presentation of subliminal threat stimuli generates increased activation of limbic structures, including the amygdala and insula, as well as emotionally evaluative structures, including the cerebellum and orbitofrontal cortex. Posttraumatic stress disorder (PTSD) is associated with an increased startle response and decreased extinction learning to conditioned threat. The role of the innate alarm system in the clinical presentation of PTSD, however, remains poorly understood. Methods Here, we compare midbrain, brainstem, and cerebellar activation in persons with PTSD (n = 26) and matched controls (n = 20) during subliminal threat presentation. Subjects were presented with masked trauma-related and neutral stimuli below conscious threshold. Contrasts of subliminal brain activation for the presentation of neutral stimuli were subtracted from trauma-related brain activation. Group differences in activation, as well as correlations between clinical scores and PTSD activation, were examined. Imaging data were preprocessed utilizing the spatially unbiased infratentorial template toolbox within SPM12. Results Analyses revealed increased midbrain activation in PTSD as compared to controls in the superior colliculus, periaqueductal gray, and midbrain reticular formation during subliminal threat as compared to neutral stimulus presentation. Controls showed increased activation in the right cerebellar lobule V during subliminal threat presentation as compared to PTSD. Finally, a negative correlation emerged between PTSD patient scores on the Multiscale Dissociation Inventory for the Depersonalization/Derealization subscale and activation in the right lobule V of the cerebellum during the presentation of subliminal threat as compared to neutral stimuli. Conclusion We interpret these findings as evidence of innate alarm system overactivation in PTSD and of the prominent role of the cerebellum in the undermodulation of emotion observed in PTSD.

Aberrant regional homogeneity in post-traumatic stress disorder after traffic accident: A resting-state functional MRI study.

ObjectivesThe present study explored the changes in spontaneous regional activity in post-traumatic stress disorder (PTSD) patients, who experienced severe traffic accidents.Methods20 drug-naive PTSD patients and 18 healthy control subjects were imaged using resting-state functional magnetic resonance imaging (rs-fMRI) and analyzed by the algorithm of regional homogeneity (ReHo).ResultsCompared to the healthy control group, the PTSD group showed decreased ReHo values in the right angular gyrus. In addition, a negative correlation was found between the activity level of the angular gyrus and the CAPS score.ConclusionThe dysfunctions were found in the memory- and emotion-related areas, suggested a possible mechanism of memory dysregulation that might be related to the intrusive memory symptoms of PTSD. These results provided imaging evidence that might provide an in-depth understanding of the intrinsic functional architecture of PTSD.

Long-Term Immune Alterations Accompanying Chronic Posttraumatic Stress Disorder following Exposure to Suicide Bomb Terror Incidents during Childhood

Background and Aim: Long-term immune alterations have been proposed to play a mechanistic role in posttraumatic stress disorder (PTSD) as well as in its associated increase in medical morbidity and mortality. Better characterization of altered immune function may help identify diagnostic and prognostic biomarkers and potentially targets for preventive intervention. Methods: As part of an ongoing study, we conducted a preliminary case-control comparison of resting immune inflammatory profiles between terror victims treated in childhood at the emergency department over the previous decade, who developed chronic PTSD upon long-term follow-up, and healthy controls. Results: Our preliminary results in a subsample of this ongoing study support and extend elevated resting levels of granulocyte colony-stimulating factor, interleukin-4, and regulated on activation, normal T cell expressed and secreted in childhood onset chronic PTSD. Conclusion: Chronic immune alterations may participate in inflammatory activation and signal to the CNS through the neurovascular unit, as well as modulate the neuroendocrine axis. Better characterization and understanding of these preliminary findings may point to diagnostic and prognostic biomarkers and potentially elucidate mechanistic involvement of immune activation in PTSD.

Neurotrophic factors and hippocampal activity in PTSD.

Although numerous studies have investigated the neurotrophic factors and hippocampal activity in posttraumatic stress disorder (PTSD) separately each other, it is unclear whether an association between neurotrophic factors and hippocampal activity is present. The aim of this study was to evaluate the functional changes in hippocampus before and after treatment with escitalopram and to associate these changes with peptides related to neuronal growth in patients with chronic PTSD and trauma survivors without PTSD. Fifteen earthquake survivors with chronic PTSD and thirteen drug naïve trauma exposed individuals without PTSD underwent fMRI scans in a block design. Serum levels of Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) were measured before and after 12 weeks treatment with escitalopram. Baseline median serum level of NGF was significantly lower in patients with chronic PTSD than trauma survivors; however, 12 weeks of treatment with escitalopram significantly increased it. Higher activation was found both in left and right hippocampus for chronic PTSD group than trauma survivors. Treatment with escitalopram was significantly associated with suppression of the hyperactivation in left hippocampus in patients with chronic PTSD. Bilateral hyperactivation in hippocampus and lowered NGF may associate with neurobiological disarrangements in chronic PTSD. Treatment with escitalopram was significantly associated with both improvement in the severity of PTSD symptoms and biological alterations. Patients diagnosed with PTSD may have further and complicated deteriorations in hippocampal networks and neurotransmitter systems than individuals who had not been diagnosed with PTSD following the same traumatic experience.

Endogenous salivary α-amylase does not interact with skin conductance response during fear extinction in posttraumatic stress disorder

Posttraumatic Stress Disorder (PTSD) is associated with elevated noradrenergic signaling, which has an impact on emotional learning and memory. Fear extinction is thought to underlie the processes of exposure therapy, however the relationship between noradrenaline and extinction in PTSD is unclear. Participants with PTSD (n = 21), trauma-exposure without PTSD (TC; n = 36), and non-trauma-exposed controls (NTC; n = 27) completed a fear conditioning and extinction paradigm, and conditioned fear was indexed by skin conductance response (SCR). Salivary α-amylase (sAA) collected at baseline and immediately post-fear acquisition was used as an index of noradrenaline, and we examined whether sAA in response to fear acquisition was a moderator between fear extinction and PTSD symptoms. While there was a significant increase in sAA from baseline to post-fear acquisition, this was not modulated by group. Compared to TC and NTC, the PTSD group displayed a slower decline in SCRs during early extinction, which generalized across stimulus type, and was not moderated by sAA. These findings suggest that the relationship between fear extinction and PTSD symptoms does not change as a function of sAA levels; however previous research suggests other processes of fear learning may be associated with noradrenergic activity in PTSD.

Veterans with PTSD demonstrate amygdala hyperactivity while viewing threatening faces: A MEG study

Posttraumatic stress disorder (PTSD) is a major psychiatric disorder that is prevalent in combat veterans. Previous neuroimaging studies have found elevated amygdala activity in PTSD in response to threatening stimuli, but previous work has lacked the temporal specificity to study fast bottom-up fear responses involving the amygdala. Forty-four combat veterans, 28 with PTSD and 16 without, completed psychological testing and then a face-processing task during magnetoencephalography (MEG). The resulting MEG data were pre-processed, transformed into the time-frequency domain, and then imaged using a beamforming approach. We found that veterans with PTSD exhibited significantly stronger oscillatory activity from 50 to 450 ms in the left amygdala compared to veterans without PTSD while processing threatening faces. This group difference was not present while viewing neutral faces. The current study shows that amygdala hyperactivity in response to threatening cues begins quickly in PTSD, which makes theoretical sense as an adaptive bottom-up fear response.

The Psychoactive Agent Crocin Can Regulate Hypothalamic-Pituitary-Adrenal Axis Activity.

Post-traumatic stress disorder (PTSD) occurs following life-threatening events. The activity of the hypothalamic-pituitary-adrenal (HPA) axis, which serves as the first line of defense against stress, is dysfunctional in this disorder. The current study aimed to investigate the role of Crocin in normalizing HPA function in an animal model of PTSD induced by electric foot shock. Rats were treated with Crocin 5 min prior to stress induction. The stimulus was re-introduced after 21 days, and we measured individual behaviors such as sniffing, rearing, grooming, and freezing. Enzyme-linked immunosorbent assays were performed to measure plasma levels of Corticosterone. On day 28, after rats were weighed and sacrificed, the adrenal and thymus glands were removed and subjected to real-time polymerase chain reaction to quantify the gene expression of corticotrophin-releasing hormone (CRH), glucocorticoid receptor (GluR), and arginine vasopressin (AVP). Our results demonstrate that rats re-exposed to a stressor developed characteristic symptoms of PTSD, but these were attenuated by Crocin. Treated rats showed significant changes in CRH expression in the hypothalamus, GluR expression in the pituitary, plasma Corticosterone levels, and freezing behavior. Together, these findings suggest that Crocin can regulate HPA axis activity in PTSD. It may serve an appropriate treatment for subjects who experience a traumatic event.

Spontaneous neural activity differences in posttraumatic stress disorder: A quantitative resting-state meta-analysis and fMRI validation.

Identifying the pathophysiology of posttraumatic stress disorder (PTSD) is a critical step toward reducing its debilitating impact. Spontaneous neural activity, measured at rest using various neuroimaging techniques (e.g., regional homogeneity [ReHo], amplitude of low frequency fluctuations [ALFF]), can provide insight about baseline neurobiological factors influencing sensory, cognitive, or behavioral processes associated with PTSD. The present study used activation likelihood estimation (ALE) to conduct the largest-to-date quantitative meta-analysis of spontaneous neural activity in PTSD, including 457 PTSD cases, 292 trauma-exposed controls (TECs), and 293 non-traumatized controls (NTCs) across 22 published studies. Five regions-of-interest (ROIs) were identified where activity differed between PTSD cases and controls: one when compared to all controls (left globus pallidus), two when compared to TECs (left inferior parietal lobule [IPL] and right lingual gyrus), and two when compared to NTCs (left amygdala and right caudate head). To corroborate these results, a second analysis was conducted using resting-state functional magnetic resonance imaging on an independent sample of 205 previously-deployed US military veterans. In this analysis, converging evidence from ReHo and ALFF showed that spontaneous neural activity in the left IPL alone was positively correlated with PTSD symptom severity. This result is consistent with theoretical accounts that link left IPL activity with PTSD-relevant processes such as processing of emotional stimuli (e.g., fearful faces) and the extent that attention is captured by salient autobiographical memories. By modeling the neurobiological correlates of PTSD, we can increase our understanding of this debilitating disorder and guide the development of future clinical innovations.

Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis.

Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC).