Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Boosting oxytocin after trauma: Effects of oxytocin on fear neurocircuitry in patients with post-traumatic stress disorder

The neuropeptide oxytocin has been suggested as promising pharmacological agent to boost treatment response in post-traumatic stress disorder (PTSD). As first step to investigate the clinical potential of oxytocin in PTSD, a randomized placebo-controlled cross-over fMRI study was conducted in police officers with and without PTSD. In this PhD thesis, the effects of a single oxytocin administration on fear neurocircuitry were investigated in male and female PTSD patients. Potential anxiolytic effects of oxytocin administration were observed in PTSD patients: oxytocin resulted in decreased subjective anxiety and nervousness, dampened amygdala activity towards emotional faces and normalized aberrant amygdala functional connectivity with prefrontal areas. Additionally, oxytocin altered neural processing of negative stimuli during distraction as emotion regulation strategy in PTSD patients in as sex-dependent manner. The effects of oxytocine were dependent on baseline neural fear regulation abilities, which were related to sex and (severity of) PTSD symptoms. Therefore, investigating the effects of oxytocin on psychotherapy, while elucidating potential contextual and inter-individual moderators, is a promising avenue for future clinical research. Additionally, functional and structural connectivity alterations were investigated in PTSD patients: a meta-analysis and systematic review were performed on all currently available resting-state studies in PTSD and a diffusion tensor imaging (DTI) was conducted to investigate white matter integrity of major white matter tracts in PTSD. In line with the predominant neurocircuitry model of PTSD, findings suggested diminished functional and structural connectivity between the amygdala and prefrontal cortex in PTSD, possibly underlying diminished prefrontal top-down control over the fear response

The role of the dentate gyrus in stress-related disorders

Contains fulltext : 219508.pdf (Publisher’s version ) (Closed access)3 p

Acute stress alters the 'default' brain processing

Contains fulltext : 201213.pdf (publisher's version ) (Open Access)Active adaptation to acute stress is essential for coping with daily life challenges. The stress hormone cortisol, as well as large scale re-allocations of brain resources have been implicated in this adaptation. Stress-induced shifts between large-scale brain networks, including salience (SN), central executive (CEN) and default mode networks (DMN), have however been demonstrated mainly under task-conditions. It remains unclear whether such network shifts also occur in the absence of ongoing task-demands, and most critically, whether these network shifts are predictive of individual variation in the magnitude of cortisol stress-responses. In a sample of 335 healthy participants, we investigated stress-induced functional connectivity changes (delta-FC) of the SN, CEN and DMN, using resting-state fMRI data acquired before and after a socially evaluated cold-pressor test and a mental arithmetic task. To investigate which network changes are associated with acute stress, we evaluated the association between cortisol increase and delta-FC of each network. Stress-induced cortisol increase was associated with increased connectivity within the SN, but with decreased coupling of DMN at both local (within network) and global (synchronization with brain regions also outside the network) levels. These findings indicate that acute stress prompts immediate connectivity changes in large-scale resting-state networks, including the SN and DMN in the absence of explicit ongoing task-demands. Most interestingly, this brain reorganization is coupled with individuals’ cortisol stress-responsiveness. These results suggest that the observed stress-induced network reorganization might function as a neural mechanism determining individual stress reactivity and, therefore, it could serve as a promising marker for future studies on stress resilience and vulnerability.8 p

Emotional Control, reappraised

We are frequently challenged with situations requiring the control of our emotions, often under substantial time-pressure and rapidly changing contextual demands. Coping with those demands requires the ability to flexibly and rapidly switch between different emotional control strategies. However, this ability has been largely neglected by current neurocognitive models on emotional control. Drawing on the decision-making literature, we propose that rapid switching between alternative emotional control strategies requires the concurrent evaluation of unchosen (counterfactual) options. This model explains how an individual can adaptively change emotional control behavior to meet contextual demands and shifting goals. We propose that the neural implementation of this emotional control mechanism relies on the anterior prefrontal cortex (aPFC/lateral frontal pole), given its known role in monitoring alternative options during cognitive decision-making tasks. We reappraise meta-analytic evidence showing consistent aPFC involvement during emotional control when monitoring of alternative emotional control strategies is required, and when alternative emotional actions have high value. We conclude with emphasizing the clinical and evolutionary implications of this new framework on emotional control

Emotional Control, reappraised

Item does not contain fulltextWe are frequently challenged with situations requiring the control of our emotions, often under substantial time-pressure and rapidly changing contextual demands. Coping with those demands requires the ability to flexibly and rapidly switch between different emotional control strategies. However, this ability has been largely neglected by current neurocognitive models on emotional control. Drawing on the decision-making literature, we propose that rapid switching between alternative emotional control strategies requires the concurrent evaluation of unchosen (counterfactual) options. This model explains how an individual can adaptively change emotional control behavior to meet contextual demands and shifting goals. We propose that the neural implementation of this emotional control mechanism relies on the anterior prefrontal cortex (aPFC/lateral frontal pole), given its known role in monitoring alternative options during cognitive decision-making tasks. We reappraise meta-analytic evidence showing consistent aPFC involvement during emotional control when monitoring of alternative emotional control strategies is required, and when alternative emotional actions have high value. We conclude with emphasizing the clinical and evolutionary implications of this new framework on emotional control

The role of automatic defensive responses in the development of posttraumatic stress symptoms in police recruits: Protocol of a prospective study

Contains fulltext : 180875.pdf (publisher's version ) (Open Access)Background: Control over automatic tendencies is often compromised in challenging situations when people fall back on automatic defensive reactions, such as freeze-fight-flight responses. Stress-induced lack of control over automatic defensive responses constitutes a problem endemic to high-risk professions, such as the police. Difficulties controlling automatic defensive responses may not only impair split-second decisions under threat, but also increase the risk for and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the significance of these automatic defensive responses in the development and maintenance of trauma-related symptoms remains unclear due to a shortage of large-scale prospective studies. Objective: The 'Police-in-Action' study is conducted to investigate the role of automatic defensive responses in the development and maintenance of PTSD symptomatology after trauma exposure. Methods: In this prospective study, 340 police recruits from the Dutch Police Academy are tested before (wave 1; pre-exposure) and after (wave 2; post-exposure) their first emergency aid experiences as police officers. The two waves of data assessment are separated by approximately 15 months. To control for unspecific time effects, a well-matched control group of civilians (n = 85) is also tested twice, approximately 15 months apart, but without being frequently exposed to potentially traumatic events. Main outcomes are associations between (changes in) behavioural, psychophysiological, endocrine and neural markers of automatic defensive responses and development of trauma-related symptoms after trauma exposure in police recruits. Discussion: This prospective study in a large group of primary responders enables us to distinguish predisposing from acquired neurobiological abnormalities in automatic defensive responses, associated with the development of trauma-related symptoms. Identifying neurobiological correlates of (vulnerability for) trauma-related psychopathology may greatly improve screening for individuals at risk for developing PTSD symptomatology and offer valuable targets for (early preventive) interventions for PTSD.12 p

On the control of social approach-avoidance behavior: Neural and endocrine mechanisms

The ability to control our automatic action tendencies is crucial for adequate social interactions. Emotional events trigger automatic approach and avoidance tendencies. Although these actions may be generally adaptive, the capacity to override these emotional reactions may be key to flexible behavior during social interaction. The present chapter provides a review of the neuroendocrine mechanisms underlying this ability and their relation to social psychopathologies. Aberrant social behavior, such as observed in social anxiety or psychopathy, is marked by abnormalities in approach-avoidance tendencies and the ability to control them. Key neural regions involved in the regulation of approach-avoidance behavior are the amygdala, widely implicated in automatic emotional processing, and the anterior prefrontal cortex, which exerts control over the amygdala. Hormones, especially testosterone and cortisol, have been shown to affect approach-avoidance behavior and the associated neural mechanisms. The present chapter also discusses ways to directly influence social approach and avoidance behavior and will end with a research agenda to further advance this important research field. Control over approach-avoidance tendencies may serve as an exemplar of emotional action regulation and might have a great value in understanding the underlying mechanisms of the development of affective disorders

Individual differences in defensive freezing reactions link to anxiety, cortisol and performance under threatening situations

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