Adverse Childhood Experiences and the Consequences on Neurobiological, Psychosocial, and Somatic Conditions Across the Lifespan

Introduction: Adverse childhood experiences (ACE) such as sexual and physical abuse or neglect are frequent in childhood and constitute a massive stressor with long-lasting adverse effects on the brain, mental and physical health.The aim of this qualitative review is to present a concise overview of the present literature on the impact of ACE on neurobiology, mental and somatic health in later adulthood.Methods: The authors reviewed the existing literature on the impact of ACE on neurobiology, mental and somatic health in later adulthood and summarized the results for a concise qualitative overview.Results: In adulthood, the history of ACE can result in complex clinical profiles with several co-occurring mental and somatic disorders such as posttraumatic stress disorder, depression, borderline personality disorder, obesity and diabetes. Although a general stress effect in the development of the disorders and neural alterations can be assumed, the role of type and timing of ACE is of particular interest in terms of prevention and treatment of ACE-related mental and somatic conditions. It has been suggested that during certain vulnerable developmental phases the risk for subsequent ACE-related disorders is increased. Moreover, emerging evidence points to sensitive periods and specificity of ACE-subtypes in the development of neurobiological alterations, e.g., volumetric and functional changes in the amygdala and hippocampus.Conclusion: Longitudinal studies are needed to investigate complex ACE-related characteristics and mechanisms relevant for mental and somatic disorders by integrating state of the art knowledge and methods. By identifying and validating psychosocial and somatic risk factors and diagnostic markers one might improve the development of innovative somatic and psychological treatment options for individuals suffering from ACE-related disorders

Disgust and implicit self-concept in women with borderline personality disorder and posttraumatic stress disorder

Disgust may be a key emotion and target for psychotherapeutic interventions in borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) at explicit and implicit-automatic levels. However, automatically activated disgust reactions in individuals with these disorders have not been studied. Disgust and its correlation with childhood abuse were assessed in women with BPD, but without PTSD; women with PTSD, but without BPD; women with BPD and PTSD; and healthy women. Disgust sensitivity, anxiety and depression were measured by self-report. Implicit disgust-prone (relative to anxiety-prone) self-concept was assessed using the Implicit Association Test. Women with BPD and/or PTSD reported more disgust sensitivity than controls. The implicit self-concept among patients was more disgust-prone (relative to anxiety-prone) than in controls. Women with BPD, with PTSD, or BPD and PTSD did not differ significantly in self-reported disgust levels or implicit disgust-related self-concept. Among women with BPD and/or PTSD, current psychiatric comorbidity (major depression, anxiety disorder, eating disorder, or substance-related disorder) did not affect disgust-related variables. More severe physical abuse in childhood was associated with a more anxiety-prone (less disgust-prone) implicit self-concept. Independent of psychiatric comorbidity, disgust appears to be elevated at implicit and explicit levels in trauma-related disorders. Psychotherapeutic approaches to address disgust should take implicit processes into accoun

Behavioral and neurophysiological correlates of emotional face processing in borderline personality disorder: are there differences between men and women?

Emotional dysregulation is a core feature of borderline personality disorder (BPD);it is, for example, known to influence one's ability to read other people's facial expressions. We investigated behavioral and neurophysiological foundations of emotional face processing in individuals with BPD and in healthy controls, taking participants' sex into account. 62 individuals with BPD (25 men, 37 women) and 49 healthy controls (20 men, 29 women) completed an emotion classification task with faces depicting blends of angry and happy expressions while the electroencephalogram was recorded. The cortical activity (late positive potential, P3/LPP) was evaluated using source modeling. Compared to healthy controls, individuals with BPD responded slower to happy but not to angry faces;further, they showed more anger ratings in happy but not in angry faces, especially in those with high ambiguity. Men had lower anger ratings than women and responded slower to angry but not happy faces. The P3/LPP was larger in healthy controls than in individuals with BPD, and larger in women than in men;moreover, women but not men produced enlarged P3/LPP responses to angry vs. happy faces. Sex did not interact with behavioral or P3/LPP-related differences between healthy controls and individuals with BPD. Together, BPD-related alterations in behavioral and P3/LPP correlates of emotional face processing exist in both men and women, supposedly without sex-related interactions. Results point to a general 'negativity bias' in women. Source modeling is well suited to investigate effects of participant and stimulus characteristics on the P3/LPP generators

Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis

We report two cases of young men in whom acute heart failure due to myocarditis was diagnosed. The patients had been transferred to the intensive care unit (ICU) with commencing symptoms of acute heart failure and consecutive multiorgan failure for further treatment and to evaluate the indication for implantation of a ventricular assist device or for high urgent orthotopic heart transplantation. In both patients, the If-channel inhibitor ivabradine was administered off-label to provide selective heart rate reduction, and thus support hemodynamic stabilization. Though currently considered off-label use in patients suffering from severe hypotension and acute heart failure, the use of ivabradine may beneficially influence outcome by allowing optimization of the patient's heart rate concomitant to initial measures of clinical stabilization

COMT val158met Polymorphism and Neural Pain Processing

A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant – though moderate - effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing

The ICD-11 classification of personality disorders: a European perspective on challenges and opportunities

The 11th revision of the World Health Organization (WHO) International Classification of Diseases (ICD-11) includes a fundamentally new approach to Personality Disorders (PD). ICD-11 is expected to be implemented first in European countries before other WHO member states. The present paper provides an overview of this new ICD-11 model including PD severity classification, trait domain specifiers, and the additional borderline pattern specifier. We discuss the perceived challenges and opportunities of using the ICD-11 approach with particular focus on its continuity and discontinuity with familiar PD categories such as avoidant PD and narcissistic PD. The advent of the ICD-11 PD classification involves major changes for health care workers, researchers, administrators, and service providers as well as patients and families involved. The anticipated challenges and opportunities are put forward in terms of specific unanswered questions. It is our hope that these questions will stimulate further research and discussion among researchers and clinicians in the coming years

Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback

Background: Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. Methods: We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. Results: Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. Conclusions: This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC

Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

Background: Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods: Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek’s disease virus (MDV). Results: Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelinbound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions: The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift

Mechanisms of disturbed emotion processing and social interaction in borderline personality disorder: state of knowledge and research agenda of the German Clinical Research Unit

The last two decades have seen a strong rise in empirical research in the mechanisms of emotion dysregulation in borderline personality disorder. Major findings comprise structural as well as functional alterations of brain regions involved in emotion processing, such as amygdala, insula, and prefrontal regions. In addition, more specific mechanisms of disturbed emotion regulation, e.g. related to pain and dissociation, have been identified. Most recently, social interaction problems and their underlying neurobiological mechanisms, e.g. disturbed trust or hypersensitivity to social rejection, have become a major focus of BPD research. This article covers the current state of knowledge and related relevant research goals. The first part presents a review of the literature. The second part delineates important open questions to be addressed in future studies. The third part describes the research agenda for a large German center grant focusing on mechanisms of emotion dysregulation in BPD

Effects of aging on the stress-induced martensitic transformation and cyclic superelastic properties in Co-Ni-Ga shape memory alloy single crystals under compression

Co-Ni-Ga shape memory alloys attracted scientific attention as promising candidate materials for damping applications at elevated temperatures, owing to excellent superelastic properties featuring a fully reversible stress-strain response up to temperatures as high as 500 °C. In the present work, the effect of aging treatments conducted in a wide range of aging temperatures and times, i.e. at 300–400 °C for 0.25–8.5 h, was investigated. It is shown that critical features of the martensitic transformation are strongly affected by the heat treatments. In particular, the formation of densely dispersed γ’-nanoparticles has a strong influence on the martensite variant selection and the morphology of martensite during stress-induced martensitic transformation. Relatively large, elongated particles promote irreversibility. In contrast, small spheroidal particles are associated with excellent functional stability during cyclic compression loading of 〈001〉-oriented single crystals. In addition to mechanical experiments, a detailed microstructural analysis was performed using in situ optical microscopy and neutron diffraction. Fundamental differences in microstructural evolution between various material states are documented and the relations between thermal treatment, microstructure and functional properties are explored and rationalized