Post-traumatic stress disorder (PTSD) is a prevalent, debilitating and sometimes deadly consequence of exposure to severe psychological trauma. Although effective treatments exist for some ...individuals, they are limited. New approaches to intervention, treatment and prevention are therefore much needed. In the past few years, the field has rapidly developed a greater understanding of the dysfunctional brain circuits underlying PTSD, a shift in understanding that has been made possible by technological revolutions that have allowed the observation and perturbation of the macrocircuits and microcircuits thought to underlie PTSD-related symptoms. These advances have allowed us to gain a more translational knowledge of PTSD, have provided further insights into the mechanisms of risk and resilience and offer promising avenues for therapeutic discovery.
According to grounded cognition, words whose semantics contain sensory‐motor features activate sensory‐motor simulations, which, in turn, interact with spatial responses to produce grounded ...congruency effects (e.g., processing the spatial feature of up for sky should be faster for up vs. down responses). Growing evidence shows these congruency effects do not always occur, suggesting instead that the grounded features in a word's meaning do not become active automatically across contexts. Researchers sometimes use this as evidence that concepts are not grounded, further concluding that grounded information is peripheral to the amodal cores of concepts. We first review broad evidence that words do not have conceptual cores, and that even the most salient features in a word's meaning are not activated automatically. Then, in three experiments, we provide further evidence that grounded congruency effects rely dynamically on context, with the central grounded features in a concept becoming active only when the current context makes them salient. Even when grounded features are central to a word's meaning, their activation depends on task conditions.
Resilience in the face of major life stressors is changeable over time and with experience. Accordingly, differing sets of neurobiological factors may contribute to an adaptive stress response ...before, during, and after the stressor. Longitudinal studies are therefore particularly effective in answering questions about the determinants of resilience. Here we provide an overview of the rapidly-growing body of longitudinal neuroimaging research on stress resilience. Despite lingering gaps and limitations, these studies are beginning to reveal individual differences in neural circuit structure and function that appear protective against the emergence of future psychopathology following a major life stressor. Here we outline a neural circuit model of resilience to trauma. Specifically, pre-trauma biomarkers of resilience show that an ability to modulate activity within threat and salience networks predicts fewer stress-related symptoms. In contrast, early post-trauma biomarkers of subsequent resilience or recovery show a more complex pattern, spanning a number of major circuits including attention and cognitive control networks as well as primary sensory cortices. This novel synthesis suggests stress resilience may be scaffolded by stable individual differences in the processing of threat cues, and further buttressed by post-trauma adaptations to the stressor that encompass multiple mechanisms and circuits. More attention and resources supporting this work will inform the targets and timing of mechanistic resilience-boosting interventions.
Objective:Dissociative experiences commonly occur in response to trauma, and while their presence strongly affects treatment approaches in posttraumatic spectrum disorders, their etiology remains ...poorly understood and their phenomenology incompletely characterized. Methods to reliably assess the severity of dissociation symptoms, without relying solely on self-report, would have tremendous clinical utility. Brain-based measures have the potential to augment symptom reports, although it remains unclear whether brain-based measures of dissociation are sufficiently sensitive and robust to enable individual-level estimation of dissociation severity based on brain function. The authors sought to test the robustness and sensitivity of a brain-based measure of dissociation severity.Methods:An intrinsic network connectivity analysis was applied to functional MRI scans obtained from 65 women with histories of childhood abuse and current posttraumatic stress disorder (PTSD). The authors tested for continuous measures of trauma-related dissociation using the Multidimensional Inventory of Dissociation. Connectivity estimates were derived with a novel machine learning technique using individually defined homologous functional regions for each participant.Results:The models achieved moderate ability to estimate dissociation, after controlling for childhood trauma and PTSD severity. Connections that contributed the most to the estimation mainly involved the default mode and frontoparietal control networks. By contrast, all models performed at chance levels when using a conventional group-based network parcellation.Conclusions:Trauma-related dissociative symptoms, distinct from PTSD and childhood trauma, can be estimated on the basis of network connectivity. Furthermore, between-network brain connectivity may provide an unbiased estimate of symptom severity, paving the way for more objective, clinically useful biomarkers of dissociation and advancing our understanding of its neural mechanisms.
Navitoclax (ABT-263), an inhibitor of the pro-survival BCL-2 family proteins BCL-2, BCL-XL and BCL-W, has shown clinical efficacy in certain BCL-2-dependent haematological cancers, but causes ...dose-limiting thrombocytopaenia. The latter effect is caused by Navitoclax directly inducing the apoptotic death of platelets, which are dependent on BCL-XL for survival. Recently, ABT-199, a selective BCL-2 antagonist, was developed. It has shown promising anti-leukaemia activity in patients whilst sparing platelets, suggesting that the megakaryocyte lineage does not require BCL-2. In order to elucidate the role of BCL-2 in megakaryocyte and platelet survival, we generated mice with a lineage-specific deletion of Bcl2, alone or in combination with loss of Mcl1 or Bclx. Platelet production and platelet survival were analysed. Additionally, we made use of BH3 mimetics that selectively inhibit BCL-2 or BCL-XL. We show that the deletion of BCL-2, on its own or in concert with MCL-1, does not affect platelet production or platelet lifespan. Thrombocytopaenia in Bclx-deficient mice was not affected by additional genetic loss or pharmacological inhibition of BCL-2. Thus, BCL-2 is dispensable for thrombopoiesis and platelet survival in mice.
A new β-decay station, COnversion electrons Chasing at Orsay (COeCO), has been developed at ALTO to perform conversion electron spectroscopy studies of neutron-rich nuclei produced by photo-fission ...of a uranium carbide target. It is based on the collection of a low-energy ISOL beam on a mylar tape, and the transportation of the electrons emitted by the produced radioactive source through a magnetic field induced by two copper coils, towards a cooled Si(Li) detector. In this article, a detailed description of the new decay station and its components is given. The magnetic field induced by the coils was measured and compared to simulations performed with the COMSOL® software. The efficiency of the detection setup was estimated using a 207Bi and a 152Eu source as an off-line commissioning. Finally, the results obtained with a 96Rb radioactive beam for the on-line commissioning are presented.
Voice hearing (VH) can occur in trauma spectrum disorders (TSD) such as posttraumatic stress disorder (PTSD) and dissociative disorders. However, previous estimates of VH among individuals with TSD ...vary widely. In this study, we sought to better characterize the rate and phenomenology of VH in a sample of 70 women with TSD related to childhood abuse who were receiving care in a specialized trauma program. We compared the rate of VH within our sample using two different measures: 1) the auditory hallucination (AH) item in the Structured Clinical Interview for DSM-IV-TR (SCID), and 2) the thirteen questions involving VH in the Multidimensional Inventory of Dissociation (MID), a self-report questionnaire that comprehensively assesses pathological dissociation. We found that 45.7% of our sample met threshold for SCID AH, while 91.4% met criteria for MID VH. Receiver operating characteristics (ROC) analyses showed that while SCID AH and MID VH items have greater than chance agreement, the strength of agreement is only moderate, suggesting that SCID and MID VH items measure related but not identical constructs. Thirty-two patients met criteria for both SCID AH and at least one MID VH item ("unequivocal VH"), 32 for at least one MID VH item but not SCID AH ("ambiguous VH"), and 6 met criteria for neither ("unequivocal non-VH"). Relative to the ambiguous VH group, the unequivocal VH group had higher dissociation scores for child voices, and higher mean frequencies for child voices and Schneiderian voices. Our findings suggest that VH in women with TSD related to childhood abuse is common, but that the rate of VH depends on how the question is asked. We review prior studies examining AH and/or VH in TSD, focusing on the measures used to ascertain these experiences, and conclude that our two estimates are consistent with previous studies that used comparable instruments and patient samples. Our results add to growing evidence that VH-an experience typically considered psychotic or psychotic-like-is not equivalent to having a psychotic disorder. Instruments that assess VH apart from psychotic disorders and that capture their multidimensional nature may improve identification of VH, especially among patients with non-psychotic disorders.
Trauma-related pathological dissociation is characterized by disruptions in one's sense of self, perceptual, and affective experience. Dissociation and its trauma-related antecedents ...disproportionately impact women. However, despite the gender-related prevalence and high individual and societal costs, dissociation remains widely underappreciated in clinical practice. Moreover, dissociation lacks a synthesized neurobiological model across its subtypes. Leveraging the Triple Network Model of psychopathology, we sought to parse heterogeneity in dissociative experience by examining functional connectivity of three core neurocognitive networks as related to: (1) the dimensional dissociation subtypes of depersonalization/derealization and partially-dissociated intrusions; and, (2) the diagnostic category of dissociative identity disorder (DID). Participants were 91 women with and without: a history of childhood trauma, current posttraumatic stress disorder (PTSD), and varied levels of dissociation. Participants provided clinical data about dissociation, PTSD symptoms, childhood maltreatment history, and completed a resting-state functional magnetic resonance imaging scan. We used a novel statistical approach to assess both overlapping and unique contributions of dissociation subtypes. Covarying for age, childhood maltreatment and PTSD severity, we found dissociation was linked to hyperconnectivity within central executive (CEN), default (DN), and salience networks (SN), and decreased connectivity of CEN and SN with other areas. Moreover, we isolated unique connectivity markers associated with depersonalization/derealization in CEN and DN, to partially-dissociated intrusions in CEN, and to DID in CEN. This suggests dissociation subtypes have robust functional connectivity signatures that may serve as targets for PTSD/DID treatment engagement. Our findings underscore dissociation assessment as crucial in clinical care, in particular, to reduce gender-related health disparities.
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