Inflammation and post‐traumatic stress disorder

While post‐traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted a link between this disorder and alterations in the immune and inflammatory systems. Epidemiological studies have demonstrated that PTSD is associated with significantly increased rates of physical comorbidities in which immune dysregulation is involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, and autoimmune diseases. In line with this, a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein. Moreover, various lines of animal and human research have suggested that inflammation is not only associated with PTSD but also can play an important role in its pathogenesis and pathophysiology. In this review, we first summarize evidence suggestive of increased inflammation in PTSD. We then examine findings that suggest possible mechanisms of inflammation in this disorder in terms of two different but interrelated perspectives: putative causes of increased proinflammatory activities and potential consequences that inflammation generates. Given that there is currently a dearth of treatment options for PTSD, possibilities of new therapeutic approaches using pharmacological and non‐pharmacological treatments/interventions that have anti‐inflammatory effects are also discussed. Despite the increasing attention given to the inflammatory pathology of PTSD, there remains much to be elucidated, including more detailed mechanisms of inflammation, potential usefulness of inflammatory biomarkers as diagnostic and prognostic markers, and efficacy of novel treatment strategies targeting inflammation.     

Hippocampal subfields alterations in adolescents with post‐traumatic stress disorder

Reexperiencing symptoms in adolescent Post‐Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high‐resolution MRI images in 15 adolescents (13–18 years old) with PTSD and 24 age‐matched healthy controls. The volume of the region CA2‐3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2‐3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale‐Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2‐3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.     

Emotional brain rhythms and their impairment in post‐traumatic patients

Patients with post‐traumatic stress disorder (PTSD) suffer from a failure of cognitive control over emotional distracters. The physiological substrates of cognitive‐emotional interactions and their breakdown in disease are, however, unknown. Here, we studied brain activity in PTSD patients and healthy controls in response to emotion‐provoking pictures using electroencephalography and functional magnetic resonance imaging (fMRI). We demonstrate that in healthy individuals, emotion‐induced frontal theta rhythm modulates activity in the beta rhythm mainly in sensory‐motor regions. In contrast, in PTSD patients, beta activity is elevated irrespective of emotion, and is not modulated by frontal theta activity in response to negative emotion. EEG source localization and fMRI findings suggest that theta activity is localized to the prefrontal and anterior cingulate cortices while beta activity is localized to sensory‐motor regions. We further found that beta activity in sensory‐motor regions is related to the emotion‐induced slowing of the motor response in healthy controls while the excess frontal theta activity in PTSD is related to the intensity of negative emotional experience. These findings reveal for the first time the importance of brain electrical oscillations and coherence in emotional top‐down modulation and point to specific failure of these mechanisms in PTSD. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

White matter integrity alterations in post‐traumatic stress disorder

Post‐traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy‐five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma‐exposed age‐ and gender‐matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non‐trauma‐exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.     

Polysomnography in patients with post‐traumatic stress disorder

Aims: The purpose of the present study was to investigate sleep structure in post‐traumatic stress disorder (PTSD) patients with and without any psychiatric comorbidities. The relationship between sleep variables and measurements of clinical symptom severity were also investigated. Methods: Sleep patterns of 24 non‐medicated male PTSD patients and 16 age‐ and sex‐matched normal controls were investigated on polysomnography on two consecutive nights. Six PTSD‐only patients and 15 PTSD patients with major depressive disorder (MDD) were also compared to normal controls. Sleep variables were correlated with PTSD symptoms. Results: Compared to the normal controls, the PTSD patients with MDD had difficulty initiating sleep, poor sleep efficiency, decreased total sleep time, decreased slow wave sleep (SWS), and a reduced rapid eye movement (REM) sleep latency. The PTSD patients without any comorbid psychiatric disorders had moderately significant disturbances of sleep continuity, and decreased SWS, but no abnormalities of REM sleep. REM sleep latency was inversely proportional to the severity of startle response. SWS was found to be inversely correlated with the severity of psychogenic amnesia. Conclusions: PTSD patients have disturbance of sleep continuity, and SWS deficit, without the impact of comorbid depression on sleep. The relationship between SWS and the inability to recall an important aspect of trauma may indicate the role of sleep in the consolidation of traumatic memories. The relationship between the severity of the startle response and REM latency may suggest that REM sleep physiology shares common substrates with the symptoms of PTSD.     

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.     

Assessing impact of differential symptom functioning on post‐traumatic stress disorder (PTSD) diagnosis

This article explores the generalizability of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnostic criteria for post‐traumatic stress disorder (PTSD) to various subpopulations. Besides identifying the differential symptom functioning (also referred to as differential item functioning [DIF]) related to various background variables such as gender, marital status and educational level, this study emphasizes the importance of evaluating the impact of DIF on population inferences as made in health surveys and clinical trials, and on the diagnosis of individual patients. Using a sample from the National Comorbidity Study‐Replication (NCS‐R), four symptoms for gender, one symptom for marital status, and three symptoms for educational level were significantly flagged as DIF, but their impact on diagnosis was fairly small. We conclude that the DSM‐IV diagnostic criteria for PTSD do not produce substantially biased results in the investigated subpopulations, and there should be few reservations regarding their use. Further, although the impact of DIF (i.e. the influence of differential symptom functioning on diagnostic results) was found to be quite small in the current study, we recommend that diagnosticians always perform a DIF analysis of various subpopulations using the methodology presented here to ensure the diagnostic criteria is valid in their own studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Relationship of alexithymia and temperament and character dimensions with lifetime post‐traumatic stress disorder in male alcohol‐dependent inpatients

Aims: The purpose of the present study was to evaluate the prevalence of lifetime post‐traumatic stress disorder (PTSD) in male alcohol‐dependent inpatients and to investigate the relationship of PTSD with alexithymia and temperament and character dimensions. Methods: Participants were 156 consecutively admitted male alcohol‐dependent subjects. Patients were investigated using the Clinician‐Administered PTSD Scale (CAPS), the Toronto Alexithymia Scale (TAS‐20) and the Temperament and Character Inventory (TCI). Results: Among alcohol‐dependent inpatients 32.1% were considered as having lifetime PTSD. Mean scores of alexithymia, novelty seeking (NS), harm avoidance (HA) and self‐transcendence (ST) were higher in the PTSD group, whereas age and self‐directedness (S) were lower. Among age and other factors of TAS‐20, ‘difficulty in identifying feelings (DIF)’ predicted PTSD in a logistic regression model. When age and personality dimensions of TCI were taken as independent variables, S predicted PTSD in the logistic regression model. Finally, among subscales of TCI, ‘impulsiveness versus reflection’ (NS2) and ‘congruent second nature versus bad habits’ (S5) predicted PTSD. Conclusions: Alexithymia and personality traits, particularly high DIF and S scores are related with lifetime PTSD diagnosis, even when controlling for age among alcohol‐dependent inpatients. Causal relationships between alexithymia, personality dimensions and PTSD, and their implications on treatment are not clear and should be evaluated in longitudinal studies.