A Network Approach to Studying the Associations Between Posttraumatic Stress Disorder Symptoms and Dissociative Experiences.

In recent years, there has been a growing recognition of a dissociative subtype of posttraumatic stress disorder (D-PTSD), characterized by experiences of depersonalization (DP) and derealization (DR), among individuals with PTSD. Little is known, however, about how experiences of DP and/or DR are associated with the experience of other PTSD symptoms. The central aim of the present paper was to explore the associations among DP, DR, and other PTSD symptoms by means of a network analysis of cross-sectional data for 557 participants whose overall self-reported PTSD symptom severity warranted a probable PTSD diagnosis. Three notable findings emerged: (a) a strong association between DP and DR, (b) the identification of DP as the most central symptom in the network, and (c) the discovery that clusters of symptoms in the network were roughly consistent with DSM-5 PTSD criteria. We discuss these findings in light of some considerations, including the nature of our sample and the limits of interpreting cross-sectional network models.

Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.

Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs.

Structural brain aberrations associated with the dissociative subtype of post-traumatic stress disorder.

OBJECTIVE: One factor potentially contributing to the heterogeneity of previous results on structural grey matter alterations in adult participants suffering from post-traumatic stress disorder (PTSD) is the varying levels of dissociative symptomatology. The aim of this study was therefore to test whether the recently defined dissociative subtype of PTSD characterized by symptoms of depersonalization and derealization is characterized by specific differences in volumetric brain morphology. METHOD: Whole-brain MRI data were acquired for 59 patients with PTSD. Voxel-based morphometry was carried out to test for group differences between patients classified as belonging (n = 15) vs. not belonging (n = 44) to the dissociative subtype of PTSD. The correlation between dissociation (depersonalization/derealization) severity and grey matter volume was computed. RESULTS: Patients with PTSD classified as belonging to the dissociative subtype exhibited greater grey matter volume in the right precentral and fusiform gyri as well as less volume in the right inferior temporal gyrus. Greater dissociation severity was associated with greater volume in the right middle frontal gyrus. CONCLUSION: The results of this first whole-brain investigation of specific grey matter volume in dissociative subtype PTSD indentified structural aberrations in regions subserving the processing and regulation of emotional arousal. These might constitute characteristic biomarkers for the dissociative subtype PTSD.

Intrinsic Connectivity Networks in post-traumatic stress disorder during sub- and supraliminal processing of threat-related stimuli.

OBJECTIVE: To investigate the functional connectivity of large-scale intrinsic connectivity networks (ICNs) in post-traumatic stress disorder (PTSD) during subliminal and supraliminal presentation of threat-related stimuli. METHOD: Group independent component analysis was utilized to study functional connectivity within the ICNs most correlated with the Default-mode Network (DMN), Salience Network (SN), and Central Executive Network (CEN) in PTSD participants (n = 26) as compared to healthy controls (n = 20) during sub- and supraliminal processing of threat-related stimuli. RESULTS: Comparing patients with PTSD with healthy participants, prefrontal and anterior cingulate cortex involved in top-down regulation showed increased integration during subliminal threat processing within the CEN and SN and during supraliminal threat processing within the DMN. The right amygdala showed increased connectivity with the DMN during subliminal processing in PTSD as compared to controls. Brain regions associated with self-awareness and consciousness exhibited decreased connectivity during subliminal threat processing in PTSD as compared to controls: the claustrum within the SN and the precuneus within the DMN. CONCLUSION: Key nodes of the ICNs showed altered functional connectivity in PTSD as compared to controls, and differential results characterized sub- and supraliminal processing of threat-related stimuli. These findings enhance our understanding of ICNs underlying PTSD at different levels of conscious threat perception.

Role of morality in the experience of guilt and shame within the armed forces.

OBJECTIVE: Despite advances in our understanding of mental health issues among military forces, a large proportion of military personnel continue to exhibit deployment-related psychological issues. Recent work has identified symptoms of guilt and shame related to moral injury as contributing significantly to combat-related mental health issues. This systematic scoping review explores the association between morality and symptoms of guilt and shame within military forces. METHOD: A search of the literature pertaining to guilt, shame and morality within military samples was conducted. RESULTS: Nineteen articles were selected for review. There is strong evidence linking exposure to and the perceived perpetration of moral transgressions with experiences of guilt and shame. Critically, symptoms of guilt and shame were related to adverse mental health outcomes, particularly the onset of post-traumatic stress disorder (PTSD). No studies have explored moral judgment in conjunction with assessments of guilt or moral injury. CONCLUSION: These findings have important implications for the prevention and treatment of PTSD-related symptoms in military samples. By measuring moral judgment prior to deployment, it may be possible to predict the likelihood of incurring moral injuries and the development of associated symptoms. Early intervention programmes aimed at ameliorating guilt and shame are required to prevent the long-term development of deployment-related psychological distress.

Distinct intrinsic network connectivity patterns of post-traumatic stress disorder symptom clusters.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is considered a multidimensional disorder, with distinct symptom clusters including re-experiencing, avoidance/numbing, hyperarousal, and most recently depersonalization/derealization. However, the extent of differing intrinsic network connectivity underlying these symptoms has not been fully investigated. We therefore investigated the degree of association between resting connectivity of the salience (SN), default mode (DMN), and central executive (CEN) networks and PTSD symptom severity. METHOD: Using resting-state functional MRI data from PTSD participants (n = 21), we conducted multivariate analyses to test whether connectivity of extracted independent components varied as a function of re-experiencing, avoidance/numbing, hyperarousal, and depersonalization/derealization. RESULTS: Hyperarousal symptoms were associated with reduced connectivity of posterior insula/superior temporal gyrus within SN [peak Montréal Neurological Institute (MNI): -44, -8, 0, t = -4.2512, k = 40]. Depersonalization/derealization severity was associated with decreased connectivity of perigenual anterior cingulate/ventromedial prefrontal cortex within ventral anterior DMN (peak MNI: 8, 40, -4; t = -3.8501; k = 15) and altered synchrony between two DMN components and between DMN and CEN. CONCLUSION: Our results are consistent with prior research showing intrinsic network disruptions in PTSD and imply heterogeneous connectivity patterns underlying PTSD symptom dimensions. These findings suggest possible biomarkers for PTSD and its dissociative subtype.

Comprehension of affective prosody in women with post-traumatic stress disorder related to childhood abuse.

OBJECTIVE: Although deficits in memory and cognitive processing are evident in post-traumatic stress disorder (PTSD), difficulties with social cognition and the impact of such difficulties on interpersonal functioning are poorly understood. Here, we examined the ability of women diagnosed with PTSD related to childhood abuse to discriminate affective prosody, a central component of social cognition. METHOD: Women with PTSD and healthy controls (HCs) completed two computer-based tasks assessing affective prosody: (i) recognition (categorizing foreign-language excerpts as angry, fearful, sad, or happy) and (ii) discrimination (identifying whether two excerpts played consecutively had the 'same' or 'different' emotion). The association of performance with symptom presentation, trauma history, and interpersonal functioning was also explored. RESULTS: Women with PTSD were slower than HCs at identifying happiness, sadness, and fear, but not anger in the speech excerpts. The presence of dissociative symptoms was related to reduced accuracy on the discrimination task. An increased severity of childhood trauma was associated with reduced accuracy on the discrimination task and with slower identification of emotional prosody. CONCLUSION: Exposure to childhood trauma is associated with long-term, atypical development in the interpretation of prosodic cues in speech. The findings have implications for the intergenerational transmission of trauma.

Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis.

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. Across k=36 independent samples and n=14,991 participants, trauma exposure was positively associated with C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α (mean rs =0.2455, 0.3067, 0.2890, and 0.2998, respectively). No significant relationships were noted with fibrinogen, IL-2, IL-4, IL-8, or IL-10. In meta-regression models, the presence of psychiatric symptoms was a significant predictor of increased effect sizes for IL-1ß and IL-6 (ß=1.0175 and 0.3568, respectively), whereas study quality assessment scores were associated with increased effect sizes for IL-6 (ß=0.3812). Positive correlations between inflammation and trauma exposure across a range of sample types and diagnoses were found. Although reviewed studies spanned an array of populations, research on any one specific psychiatric diagnosis was generally limited to one or two studies. The results suggest that chronic inflammation likely represents one potential mechanism underlying risk of health problems in trauma survivors.

Theory of mind performance in women with posttraumatic stress disorder related to childhood abuse.

OBJECTIVE: Key questions remain unaddressed concerning the nature of interpersonal functioning in trauma survivors, including the ability to understand and interpret other people's thoughts and feelings. Here, we investigate theory of mind (ToM) performance of women with PTSD related to childhood abuse in comparison to healthy controls. METHOD: Participants completed two ToM tasks, the Interpersonal Perception Task-15 (IPT-15) and the Reading the Mind in the Eyes Task - Revised (RMET). RESULTS: Relative to controls, women with a history of childhood trauma had difficulty recognizing familial relationships depicted in the IPT-15 (P = 0.005). No other category of the IPT-15 showed significant group differences. In addition, while healthy women displayed faster RMET reaction times to emotionally valenced mental states (positive: P = 0.003; negative: P = 0.016) compared with neutral mental states, the PTSD group showed similar reaction times across all valences. The presence of dissociative symptoms (e.g., disengagement, amnesia, identity dissociation) was strongly associated with hindered accuracy of complex mental state identification and altered perception of kinship interactions. CONCLUSION: Women with PTSD stemming from childhood trauma show changes in ToM abilities particularly those often involved in the interpretation of family interactions. In addition, individuals with PTSD showed slower reaction times during the recognition of complex mental states from emotionally salient facial/eye expressions in comparison with healthy subjects.

Plastic modulation of PTSD resting-state networks and subjective wellbeing by EEG neurofeedback.

OBJECTIVE: Electroencephalographic (EEG) neurofeedback training has been shown to produce plastic modulations in salience network and default mode network functional connectivity in healthy individuals. In this study, we investigated whether a single session of neurofeedback training aimed at the voluntary reduction of alpha rhythm (8-12 Hz) amplitude would be related to differences in EEG network oscillations, functional MRI (fMRI) connectivity, and subjective measures of state anxiety and arousal in a group of individuals with post-traumatic stress disorder (PTSD). METHOD: Twenty-one individuals with PTSD related to childhood abuse underwent 30 min of EEG neurofeedback training preceded and followed by a resting-state fMRI scan. RESULTS: Alpha desynchronizing neurofeedback was associated with decreased alpha amplitude during training, followed by a significant increase ('rebound') in resting-state alpha synchronization. This rebound was linked to increased calmness, greater salience network connectivity with the right insula, and enhanced default mode network connectivity with bilateral posterior cingulate, right middle frontal gyrus, and left medial prefrontal cortex. CONCLUSION: Our study represents a first step in elucidating the potential neurobehavioural mechanisms mediating the effects of neurofeedback treatment on regulatory systems in PTSD. Moreover, it documents for the first time a spontaneous EEG 'rebound' after neurofeedback, pointing to homeostatic/compensatory mechanisms operating in the brain.

Gray matter volume alterations related to trait dissociation in PTSD and traumatized controls.

OBJECTIVE: This study used voxel-based morphometry (VBM) to investigate brain structural alterations related to trait dissociation and its relationship with post-traumatic stress disorder (PTSD). METHOD: Thirty-two subjects either developing (N = 15) or non-developing (N = 17) PTSD underwent MRI scanning and were assessed with the Dissociative Experience Scale (DES), subscales for pathological (DES-T) and non-pathological trait (DES-A) dissociation, and other clinical measures. Gray matter volume (GMV) was analyzed using VBM as implemented in SPM. PTSD and non-PTSD subjects were compared to assess brain alterations related to PTSD pathology, whereas correlation analyses between dissociation measures and GMV were performed on the whole sample (N = 32), irrespective of PTSD diagnosis, to identify alterations related to trait dissociation. RESULTS: As compared to traumatized controls, PTSD subjects showed reduced GMV in the prefrontal cortex, hippocampus and lingual gyrus. Correlations with dissociation measures (DES, DES-T, and DES-A) consistently showed increased GMV in the medial and lateral prefrontal, orbitofrontal, parahippocampal, temporal polar, and inferior parietal cortices. CONCLUSION: PTSD and dissociation seem to be associated with opposite volumetric patterns in the prefrontal cortex. Trait dissociation appears to involve increased GMV in prefrontal, paralimbic, and parietal cortices, with negligible differences between pathological and non-pathological dissociation.

Neural correlates of self-reflection in post-traumatic stress disorder.

OBJECTIVE: Disturbances in self-referential processing (SRP) are increasingly recognized in post-traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP. METHOD: We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T. RESULTS: Controls made faster responses to the self-relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self-relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self-relevance of personal characteristics relative to general facts. CONCLUSIONS: These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self-referential cognition and identity-existential disturbance as diagnostically relevant to PTSD.

How understanding the neurobiology of complex post-traumatic stress disorder can inform clinical practice: a social cognitive and affective neuroscience approach.

OBJECTIVE: In this review, we examine the relevance of the social cognitive and affective neuroscience (SCAN) paradigm for an understanding of the psychology and neurobiology of complex post-traumatic stress disorder (PTSD) and its effective treatment. METHOD: The relevant literature pertaining to SCAN and PTSD was reviewed. RESULTS: We suggest that SCAN offers a novel theoretical paradigm for understanding psychological trauma and its numerous clinical outcomes, most notably problems in emotional/self-awareness, emotion regulation, social emotional processing and self-referential processing. A core set of brain regions appear to mediate these collective psychological functions, most notably the cortical midline structures, the amygdala, the insula, posterior parietal cortex and temporal poles, suggesting that problems in one area (e.g. emotional awareness) may relate to difficulties in another (e.g. self-referential processing). We further propose, drawing on clinical research, that the experiences of individuals with PTSD related to chronic trauma often reflect impairments in multiple social cognitive and affective functions. CONCLUSION: It is important that the assessment and treatment of individuals with complex PTSD not only addresses traumatic memories but also takes a SCAN-informed approach that focuses on the underlying deficits in emotional/self-awareness, emotion regulation, social emotional processing and self-referential processing.

Cognitive distortions in an acutely traumatized sample: an investigation of predictive power and neural correlates.

BACKGROUND: Current theories of post-traumatic stress disorder (PTSD) place considerable emphasis on the role cognitive distortions such as self-blame, hopelessness or preoccupation with danger play in the etiology and maintenance of the disorder. Previous studies have shown that cognitive distortions in the early aftermath of traumatic events can predict future PTSD severity but, to date, no studies have investigated the neural correlates of this association. METHOD: We conducted a prospective study with 106 acutely traumatized subjects, assessing symptom severity at three time points within the first 3 months post-trauma. A subsample of 20 subjects additionally underwent a functional 4-T magnetic resonance imaging (MRI) scan at 2 to 4 months post-trauma. RESULTS: Cognitive distortions proved to be a significant predictor of concurrent symptom severity in addition to diagnostic status, but did not predict future symptom severity or diagnostic status over and above the initial symptom severity. Cognitive distortions were correlated with blood oxygen level-dependent (BOLD) signal strength in brain regions previously implicated in visual processing, imagery and autobiographic memory recall. Intrusion characteristics accounted for most of these correlations. CONCLUSIONS: This investigation revealed significant predictive value of cognitive distortions concerning concurrent PTSD severity and also established a significant relationship between cognitive distortions and neural activations during trauma recall in an acutely traumatized sample. These data indicate a direct link between the extent of cognitive distortions and the intrusive nature of trauma memories.

Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects.

OBJECTIVE: The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in a sample of eleven acutely traumatized subjects. METHOD: Participants underwent a 5.5 min resting functional magnetic resonance imaging scan. Brain areas whose activity positively correlated with that of the posterior cingulate/precuneus (PCC) were assessed. To assess the relationship between severity of PTSD symptoms and PCC connectivity, the contrast image representing areas positively correlated with the PCC was correlated with the subjects' Clinician Administered PTSD Scale scores. RESULTS: Results suggest that resting state connectivity of the PCC with the perigenual anterior cingulate and the right amygdala is associated with current PTSD symptoms and that correlation with the right amygdala predicts future PTSD symptoms. CONCLUSION: These results may contribute to the development of prognostic tools to distinguish between those who will and those who will not develop PTSD.

The role of beta-endorphin in the pathophysiology of major depression.

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta-END in the pathophysiology of MDD must be paralleled by consensus building within the research community around the heterogeneity inherent in mood disorders, standardization of experimental protocols, improved discrimination of POMC products in analytical techniques and consistent attention paid to important confounds like age and gender.

A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation.

Different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation in posttraumatic stress disorder (PTSD) have been reported in the literature. Two subtypes of trauma response have been hypothesized, one characterized predominantly by hyperarousal and the other primarily dissociative, each one representing unique pathways to chronic stress-related psychopathology. Recent PTSD neuroimaging findings in our own laboratory support this notion and are consistent with the view that grouping all PTSD subjects, regardless of their different symptom patterns, in the same diagnostic category may interfere with our understanding of posttrauma psychopathology. This review will integrate findings of different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation with the clinical symptomatology and the neurobiology of PTSD.

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Protein kinase C activity and protein levels in Alzheimer's disease.

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in the levels and activities of protein kinase C (PKC) in brain and other tissues. We have measured Ca2+-activated, phospholipid-dependent PKC activities and levels in cerebral cortex from frontal, motor, temporal and parietal regions, as well as in leukocytes and platelets from AD patients and controls. No significant differences in PKC histone H1 phosphotransferase activity were seen in frontal, motor, temporal or parietal cortex, or in leukocytes and platelets from AD patients and controls. Elevated PKC protein was present in cytosolic fractions from frontal cortex, but not in other brain regions, or in leukocytes and platelets. These data suggest that abnormalities of PKC phosphorylating activity are absent in AD.