Intact GR dimerization is critical for restraining plasma ACTH levels during chronic psychosocial stress.

Male C57BL/6N mice exposed to the chronic subordinate colony housing (CSC; 19 days) paradigm, a preclinically validated model of chronic psychosocial stress, are characterized by unaffected basal morning plasma corticosterone (CORT) concentrations despite adrenal and pituitary hyperplasia and increased adrenocorticotropic hormone (ACTH) plasma concentrations, compared with single-housed control (SHC) mice. However, as CSC mice are still able to show an increased CORT secretion towards novel heterotypic stressors, these effects might reflect an adaptation rather than a functional breakdown of general hypothalamus-pituitary-adrenal (HPA) axis functionality. In the present study we used male mice of a genetically modified mouse line, to investigate whether genetically-driven ACTH overexpression compromises adaptational processes occurring at the level of the adrenals during CSC exposure. Experimental mice carried a point mutation in the DNA binding domain of the glucocorticoid (GC) receptor (GR), attenuating dimerization of GR (GRdim), resulting in a congenially compromised negative feedback inhibition at the level of the pituitary. In line with previous studies, CSC mice in both the wild type (WT; GR+/+) and GRdim group developed adrenal enlargement. Moreover, compared with respective SHC and WT mice, CSC GRdim mice show increased basal morning plasma ACTH and CORT concentrations. Quantitative polymerase chain reaction (qPCR) analysis revealed neither a genotype effect, nor a CSC effect on pituitary mRNA expression of the ACTH precursor proopiomelanocortin (POMC). Finally, CSC increased anxiety-related behavior, active coping and splenocyte in vitro (re)activity in both WT and GRdim mice, while a CSC-induced increase in adrenal lipid vesicles and splenic GC resistance was detectable only in WT mice. Of note, lipopolysaccharide (LPS)-stimulated splenocytes of GRdim mice were resistant to the inhibitory effects of CORT. Together our findings support the hypothesis that pituitary ACTH protein concentration is negatively controlled by GR dimerization under conditions of chronic psychosocial stress, while POMC gene transcription is not dependent on intact GR dimerization under both basal and chronic stress conditions. Finally, our data suggest that adrenal adaptations during chronic psychosocial stress (i.e., ACTH desensitization), aiming at the prevention of prolonged hypercorticism, are protective only to a certain threshold of plasma ACTH levels.

Spider Phobia: Neural Networks Informing Diagnosis and (Virtual/Augmented Reality-Based) Cognitive Behavioral Psychotherapy-A Narrative Review.

Recent fMRI studies on specific animal phobias, particularly spider phobia (arachnophobia), have identified a large variety of specific brain regions involved in normal and disturbed fear processing. Both functional and structural brain abnormalities have been identified among phobic patients. Current research suggests that both conscious and subconscious fear processing play a crucial role in phobic disorders. Cognitive behavioral therapy has been identified as an effective treatment for specific phobias and has been associated with neuroplastic effects which can be evaluated using current neuroimaging techniques. Recent research suggests that new approaches using virtual (VR) or augmented reality (AR) tend to be similarly effective as traditional "in vivo" therapy methods and could expand treatment options for different medical or individual scenarios. This narrative review elaborates on neural structures and particularities of arachnophobia. Current treatment options are discussed and future research questions are highlighted.

Transgenerational Transmission of Trauma across Three Generations of Alevi Kurds.

BACKGROUND: Thus far, most researchers on genocide and transgenerational transmissions have focused on the National Socialist Holocaust as the most abhorrent example of this severe human rights violation. Few data have been published on other ethnic or religious groups affected by genocidal actions in this context. METHODOLOGY: Using a mixed-method approach integrating qualitative interviews with standardized instruments (SCID and PDS), this study examines how individual and collective trauma have been handed down across three generations in an Alevi Kurd community whose members (have) suffered genocidal perpetrations over a longer time period (a "genocidal environment"). Qualitative, open-ended interviews with members of three generations answering questions yielded information on (a) how their lives are shaped by the genocidal experiences from the previous generation and related victim experiences, (b) how the genocidal events were communicated in family narratives, and (c) coping strategies used. The first generation is the generation which directly suffered the genocidal actions. The second generation consists of children of those parents who survived the genocidal actions. Together with their family (children, partner, relatives), this generation suffered forced displacement. Members of the third generation were born in the diaspora where they also grew up. RESULTS: Participants reported traumatic memories, presented in examples in this publication. The most severe traumatic memories included the Dersim massacre in 1937-1938 in Turkey, with 70,000-80,000 victims killed, and the enforced resettlement in western Turkey. A content analysis revealed that the transgenerational transmission of trauma continued across three generations. SCID and PDS data indicated high rates of distress in all generations. CONCLUSIONS: Genocidal environments such as that of the Kurdish Alevis lead to transgenerational transmission mediated by complex factors.

Shame, dissociative seizures and their correlation among traumatised female Yazidi with experience of sexual violence.

BACKGROUND: Survivors of Islamic State of Iraq and Syria (ISIS) captivity are at high risk of developing mental disorders such as post-traumatic stress disorder (PTSD). AIMS: This study looks at the correlation between sexual abuse, shame, somatoform or bodily distress disorders, and dissociative seizures (psychogenic non-epileptic seizures). METHOD: The psychological effects of traumatic events and dissociative seizure were assessed in Yazidi women who were held captive by ISIS in Northern Iraq between 2014 and 2018. These effects were examined comparing 64 women who were held captive and sexually abused by ISIS with 60 women suffering from PTSD who were not held captive and sexually abused by ISIS. Structured clinical-psychological interviews and established psychometric questionnaires were used to assess mental disorders especially dissociative seizures and somatoform disorders, and shame related to trauma. RESULTS: Women who were held captive by ISIS showed a significantly higher prevalence of dissociative seizures (43.7%; P = 0.02) and somatisation disorder (38.7%; P = 0.02), as well as depressive (75.0%; P = 0.42) and anxiety disorders (62.5%; P = 0.44), than women who were not held captive and sexually abused by ISIS. Dissociative disorders were identified in 40.6% (P = 0.36) of those female Yazidi who experienced sexual violence while being held captive. CONCLUSIONS: Shame in connection with sexual violence seems to play an important role in negative self-perception after rape. Dissociation not only plays an important role in unprocessed childhood trauma with feelings of shame, but also in more recent trauma experiences with shame.

Self-Contempt as a Predictor of Suicidality: A Longitudinal Study.

People with mental illness can internalize public prejudice and negative emotional reactions to their group, leading to self-contempt. This study examined self-contempt related to having a mental illness as predictor of suicidality among 77 people with mental illness in Southern Germany. Self-contempt, depressive symptoms, hopelessness, and suicidality were assessed at baseline; suicidality was measured again 3 months later. High self-contempt at baseline predicted increased suicidality at follow-up, adjusting for baseline suicidality, symptoms, diagnosis, age, sex, and hopelessness. These results suggest that self-contempt may be a risk factor for suicidality and call for specific interventions targeting self-stigma and its emotional consequences.

The role of hedonics in the Human Affectome.

Experiencing pleasure and displeasure is a fundamental part of life. Hedonics guide behavior, affect decision-making, induce learning, and much more. As the positive and negative valence of feelings, hedonics are core processes that accompany emotion, motivation, and bodily states. Here, the affective neuroscience of pleasure and displeasure that has largely focused on the investigation of reward and pain processing, is reviewed. We describe the neurobiological systems of hedonics and factors that modulate hedonic experiences (e.g., cognition, learning, sensory input). Further, we review maladaptive and adaptive pleasure and displeasure functions in mental disorders and well-being, as well as the experience of aesthetics. As a centerpiece of the Human Affectome Project, language used to express pleasure and displeasure was also analyzed, and showed that most of these analyzed words overlap with expressions of emotions, actions, and bodily states. Our review shows that hedonics are typically investigated as processes that accompany other functions, but the mechanisms of hedonics (as core processes) have not been fully elucidated.

Post-traumatic stress disorder among former Islamic State child soldiers in northern Iraq.

BACKGROUND: Former child soldiers are at high risk of developing mental disorders such as post-traumatic stress disorder (PTSD); however, their comprehensive mental health has yet to be examined.AimsThis study looks at the prevalence of PTSD, depression and associated risk factors such as disturbed self-esteem among former child soldiers of the so-called 'Islamic State'. METHOD: The psychological effect of traumatic events was assessed in 81 Yazidi children who had been child soldiers for the Islamic State in northern Iraq between 2014 and 2017 for at least 6 months. The children were between 8 and 14 years of age. Thirty-two Yazidi boys and 31 Muslim boys who were not child soldiers in Iraq served as control groups. A structured psychological interview and established psychometric questionnaires were used to assess traumatisation and mental disorders. RESULTS: The child soldiers showed a significantly higher prevalence of PTSD (48.3%), depressive disorders (45.6%), anxiety disorders (45.8%) and somatic disturbances (50.6%) than the boys who had not been child soldiers. Developmentally crucial self-esteem was significantly reduced in former child soldiers. No significant differences between the two control groups could be found. CONCLUSIONS: PTSD and other mental disorders are highly present among former child soldiers in northern Iraq. The study highlights the huge and as yet unmet need for psychological services among former child soldiers.Declaration of interestNone.

Cortical Thickness Alterations in Chronic Pain Disorder: An Exploratory MRI Study.

OBJECTIVE: Chronic pain disorder (CPD) has been associated with brain changes, especially in limbic circuits. However, in most patients with chronic pain, depression or anxiety is a common comorbidity. In this exploratory and naturalistic study, we investigated brain cortical thickness (CTh) differences between patients with CPD and healthy controls, with consideration of concurrent psychiatric symptoms. METHODS: Twenty-three patients with CPD and 23 age- and sex-matched healthy volunteers were included in this study. CTh was estimated using Freesurfer on high-resolution three-dimensional T1-weighted images acquired with a 3T scanner. Group differences were investigated using an analysis of covariance model that included age, sex, and Beck Depression Inventory I and Trait Anxiety Inventory scores as covariates. The relationship between CTh and Toronto Alexithymia Scale (TAS-20) scores was also investigated in patients. Data were corrected for multiplicity using the False Discovery Rate approach (q < .05). RESULTS: The comparison between groups using demographics and Beck Depression Inventory I scores as covariates showed thinner cortex in patients compared with controls, after correction for multiplicity in the left precentral (F(1,42) = 21.9, p < .05) and postcentral gyri (F(1,42) = 26.9, p < .05) and in the left inferior temporal sulcus (F(1,42) = 19.6, p < .05). Moreover, using the Trait Anxiety Inventory as covariate, a trend toward significance (p < .001 uncorrected) was seen for the left precentral gyrus (F(1,42) = 13.8), right middle frontal (F(1,42) = 14.3) and inferior parietal gyri (F(1,42) = 13.4), and right anterior temporal pole (F(1,42) = 15.9). CONCLUSIONS: The results indicate that brain morphological differences between patients with chronic pain disorder and healthy controls are localized to regions that correspond to sensory as well as affective dimensions of pain processing.

Bee Stings and Chronic Pain Disorder.

Chronic pain is a major problem of public health, and patients seek manifold forms of help to find relief. Here we present and discuss the case of a middle-aged woman suffering from mental disorders who treated her headache with the self-application of bee stings on her back.

Individual, collective, and transgenerational traumatization in the Yazidi.

In recent years, Islamic terrorism has manifested itself with an unexpectedly destructive force. Despite the fact that Islamic terrorism commences locally in most cases, it has spread its terror worldwide. In August 2014, when troops of the self-proclaimed 'Islamic State' conquered areas of northern Iraq, they turned on the long-established religious minorities in the area with tremendous brutality, especially towards the Yazidis. Vast numbers of men were executed, and women and children were abducted and willfully subjected to sexual violence. With the aim of systematic destruction of the Yazidi community, the religious minority was to be eliminated and the will of the victims broken. The medical and mental health issues arising from the combination of subjective, collective, and cultural traumatization, as well as the subsequent migrant and refugee crisis, are therefore extraordinary and require novel and wise concepts of integrated medical care.

Whiplash Syndrome Reloaded: Digital Echoes of Whiplash Syndrome in the European Internet Search Engine Context.

BACKGROUND: In many Western countries, after a motor vehicle collision, those involved seek health care for the assessment of injuries and for insurance documentation purposes. In contrast, in many less wealthy countries, there may be limited access to care and no insurance or compensation system. OBJECTIVE: The purpose of this infodemiology study was to investigate the global pattern of evolving Internet usage in countries with and without insurance and the corresponding compensation systems for whiplash injury. METHODS: We used the Internet search engine analytics via Google Trends to study the health information-seeking behavior concerning whiplash injury at national population levels in Europe. RESULTS: We found that the search for "whiplash" is strikingly and consistently often associated with the search for "compensation" in countries or cultures with a tort system. Frequent or traumatic painful injuries; diseases or disorders such as arthritis, headache, radius, and hip fracture; depressive disorders; and fibromyalgia were not associated similarly with searches on "compensation." CONCLUSIONS: In this study, we present evidence from the evolving viewpoint of naturalistic Internet search engine analytics that the expectations for receiving compensation may influence Internet search behavior in relation to whiplash injury.

Posttraumatic Stress Disorder and Related Disorders among Female Yazidi Refugees following Islamic State of Iraq and Syria Attacks-A Case Series and Mini-Review.

Following the severe attacks by the so-called "Islamic State of Iraq and Syria" on the Yazidi population, which started in summer 2014, the state government of Baden-Württemberg, Germany, funded a Special-Quota Project to bring 1,000 very ill or left-behind women and children who were being held hostage to 22 cities and towns in Baden-Württemberg to receive integrated care. Here, we report for the first time on the cases of four Yazidi women living in Ulm, Germany, focusing on the clinically observed and psychometrically assessed mental phenomena or disorders. Our primary aim was to explore what International Classification of Diseases, 10th Revision diagnoses are present in this population. Although highly traumatized, these women were suffering primarily from adjustment disorder rather than posttraumatic stress disorder according to official classification systems. Despite their symptoms of depression and anxiety, the women's responses to self-assessment questionnaires provided no evidence of compulsion, somatization, or eating disorders. The results suggest that further investigation of the individual-level effects of rape and torture, as well the historic, systemic, and collective effects, e.g., on families and societies, is required.

[Functional and Somatoform Disorders in the Mirror of ICD-10 Routine Data]. / Funktionelle und somatoforme Störungen im Spiegel von ICD-10-Routinedaten.

The ICD-10 offers the possibility of double coding of diagnoses in functional disorders on the one hand, somatoform disorders on the other side. The current S3 guideline for "dealing with patients with non-specific, functional and somatoform physical complaints" states that "[...] in most cases, the specialty of the (initial) examiner and not the clinical constellation seems to define how a diagnosis is made". Based on selective routine data of the Daimler BKK for the years 2008-2010 frequencies of specific functional diagnoses were compared with those of somatoform disorders, additional diagnoses analyzed and compared with epidemiological data from the Federal Health Monitoring System. The incidence found in epidemiological studies of somatoform disorders cannot be found in present routine data. Functional disorders were more frequently diagnosed than somatoform disorders. Certain additional diagnoses that may provide clues to etiological relations are rarely used. As the validity, reliability and purpose of ICD-10 invoicing diagnoses is debatable, there seems to be an imbalance relevant for the health care system. Non-adherence to the guidelines may prevent adequate quality and quantity of patient care.

Is the Medial Prefrontal Cortex Necessary for Theory of Mind?

BACKGROUND: Successful social interaction relies on the ability to attribute mental states to other people. Previous functional neuroimaging studies have shown that this process, described as Theory of Mind (ToM) or mentalization, is reliably associated with activation of the medial prefrontal cortex (mPFC). However, this study presents a novel and surprising finding that provides new insight into the role of the mPFC in mentalization tasks. METHODOLOGY/PRINCIPAL FINDINGS: Twenty healthy individuals were recruited from a wide range of ages and social backgrounds. Participants underwent functional magnetic resonance imaging (fMRI) while viewing a well-established ToM visual paradigm involving moving triangles. Functional MRI data were analyzed using a classical general linear model. No activation was detected in the medial prefrontal cortex (mPFC) during movement patterns that typically elicit ToM. However, increased activity was observed in the right middle occipital gyrus, right temporoparietal junction (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No correlation was found between participants' age and BOLD response. CONCLUSIONS/SIGNIFICANCE: In contrast with previous neuroimaging research, our findings support the notion that mPFC function is not critical for reasoning about the mental states of others; furthermore, our data indicate that the right TPJ and right inferior frontal gyrus are able to perform mentalization without any contributions from the mPFC.

Caloric vestibular stimulation as a treatment for conversion disorder: a case report and medical hypothesis.

Conversion disorder is a medical condition in which a person has paralysis, blindness, or other neurological symptoms that cannot be clearly explained physiologically. To date, there is neither specific nor conclusive treatment. In this paper, we draw together a number of disparate pieces of knowledge to propose a novel intervention to provide transient alleviation for this condition. As caloric vestibular stimulation has been demonstrated to modulate a variety of cognitive functions associated with brain activations, especially in the temporal-parietal cortex, anterior cingulate cortex, and insular cortex, there is evidence to assume an effect in specific mental disorders. Therefore, we go on to hypothesize that lateralized cold vestibular caloric stimulation will be effective in treating conversion disorder and we present provisional evidence from one patient that supports this conclusion. If our hypothesis is correct, this will be the first time in psychiatry and neurology that a clinically well-known mental disorder, long considered difficult to understand and to treat, is relieved by a simple or common, non-invasive medical procedure.

[The role of stress axes in cancer incidence and proliferation]. / Die Rolle der Stressachsen in der Entstehung und Proliferation einer Krebserkankung.

Psychosocial stressors can modulate the different stages of neoplastic events. It is established that there is activation of 2 well-known stress axes under stress, the hypothalamic-pituitary-adrenal axis and sympatho-adrenal-medullary axis, where especially the proliferating promoting effects on the malignant tumor events are known to depend on ß-adrenergic receptors. A new model focuses on the positive activating stress, which leads through the activation of the sympathetic hypothalamic-adipocyte axis to inhibition of tumor growth and reduction of obesity. This leads in mice to increased gene expression of the neurotrophin BDNF, which activates the sympathetic fibers of the white adipose tissue. Over consecutive stimulation of the ß-adrenergic receptors and thus the release of leptin, its promotional effect on the tumor growth is inhibited. In the clinical context, these results support the role of complex ß-adrenergic signal transduction pathways.