Plasma Endocannabinoid Levels in Patients with Borderline Personality Disorder and Healthy Controls.

Borderline personality disorder (BPD) is a highly prevalent psychiatric disorder and presents a complex therapeutic challenge due to limited treatment modalities. Recent focus has converged on the endocannabinoid system (ECS) as a prospective modulator of psychopathological processes in BPD. To address this hypothesis, we analysed plasma endocannabinoid concentrations, specifically anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in a cohort of 49 female BPD patients and 32 matched healthy controls (HC). Additionally, we examined the effect of the FAAH polymorphism rs324420 and correlates with psychopathology. The results indicate heightened AEA levels and, by trend, augmented 2-AG levels within the patient group, as compared to the HC group. Significant between group differences in AEA levels were evident in the CC genotype (FAAH_rs324420) but not in A-allele carriers while the commonly observed difference in AEA levels between A-allele carriers as compared to the CC genotype was not evident in patients. An effect of genotype was found with higher ratings of depression (Beck's depression inventory, BDI-II) in the CC genotype compared to A-allele carriers (FAAH_rs32442), particularly in the patients. Significant alterations in AEA (and by trend in 2-AG) in patients with BPD may relate to compensatory ECS activity. The finding that the effect is most pronounced in CC homozygotes, might point towards a countermeasure to balance physiologically lower baseline AEA levels. The findings warrant further research to develop potentially beneficial psychopharmacological therapies.

FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study.

Gold standard treatments for anxiety- and trauma-related disorders focus on exposure therapy promoting extinction learning and extinction retention. However, its efficacy is limited. Preclinical and particularly animal research has been able to demonstrate that homozygosity for the fatty acid amide hydrolase (FAAH) C385A allele, similar to FAAH inhibition, is associated with elevated concentrations of anandamide (AEA) and facilitates extinction learning and extinction recall. However, in humans, the underlying neurobiological processes are less well understood, and further knowledge might enhance the development of more effective therapies. In this functional magnetic resonance imaging (fMRI) study, a fear conditioning, fear extinction and extinction recall paradigm was conducted with 55 healthy male adults. They were genotyped for the FAAH single-nucleotide polymorphism (SNP) rs324420 to investigate differences related to extinction recall in neural activation and State-Trait Anxiety Inventory (STAI) ratings between AC heterozygotes and CC homozygotes (FAAH C385A SNP). Differential brain activation upon an unextinguished relative to an extinguished stimulus, was greater in AC heterozygotes as compared to CC homozygotes in core neural structures previously related to extinction recall, such as the medial superior frontal gyrus, the dorsal anterior cingulate and the anterior and middle insular cortex. Furthermore, AC heterozygotes displayed higher AEA levels and lower STAI-state ratings. Our data can be interpreted in line with previous suggestions of more successful extinction recall in A-allele carriers with elevated AEA levels. Data corroborate the hypothesis that the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.

First onset of treatment of patients with eating disorders and treatment course: Results of data from a German health insurance company.

OBJECTIVE: This study examines, inpatient treatment costs, and typical treatment courses of patients with an eating disorder using secondary data. METHOD: The data were provided by a German health insurance company (data from 4.2 million members from 2004 to 2010; corresponds to a market share of 6% of all statutorily insured persons in Germany). An age and gender matched control group without an eating disorder diagnosis was assessed for comparisons from the same dataset. RESULTS: Two thousand seven hundred and thirty four cases with an eating disorder diagnosis (anorexia nervosa [AN], bulimia nervosa [BN] or combination [ANBN]) were identified. The inpatient costs of treatment were €5471.15 for BN, €9080.26 for AN, €10,809.16 for ANBN and €339.37 for the control group. Interestingly, there are numerous mild episodes of eating disorders that could be successfully treated solely on an outpatient basis with a short treatment duration. CONCLUSION: Our findings suggest that course and severity of eating disorders can vary from mild to very severe. Data from health insurance companies depict rather different disease and treatment courses than studies on primary data derived from treatment institutions.

The uulmMAC Database-A Multimodal Affective Corpus for Affective Computing in Human-Computer Interaction.

In this paper, we present a multimodal dataset for affective computing research acquired in a human-computer interaction (HCI) setting. An experimental mobile and interactive scenario was designed and implemented based on a gamified generic paradigm for the induction of dialog-based HCI relevant emotional and cognitive load states. It consists of six experimental sequences, inducing Interest, Overload, Normal, Easy, Underload, and Frustration. Each sequence is followed by subjective feedbacks to validate the induction, a respiration baseline to level off the physiological reactions, and a summary of results. Further, prior to the experiment, three questionnaires related to emotion regulation (ERQ), emotional control (TEIQue-SF), and personality traits (TIPI) were collected from each subject to evaluate the stability of the induction paradigm. Based on this HCI scenario, the University of Ulm Multimodal Affective Corpus (uulmMAC), consisting of two homogenous samples of 60 participants and 100 recording sessions was generated. We recorded 16 sensor modalities including 4 × video, 3 × audio, and 7 × biophysiological, depth, and pose streams. Further, additional labels and annotations were also collected. After recording, all data were post-processed and checked for technical and signal quality, resulting in the final uulmMAC dataset of 57 subjects and 95 recording sessions. The evaluation of the reported subjective feedbacks shows significant differences between the sequences, well consistent with the induced states, and the analysis of the questionnaires shows stable results. In summary, our uulmMAC database is a valuable contribution for the field of affective computing and multimodal data analysis: Acquired in a mobile interactive scenario close to real HCI, it consists of a large number of subjects and allows transtemporal investigations. Validated via subjective feedbacks and checked for quality issues, it can be used for affective computing and machine learning applications.

Training approaches for the dissemination of clinical guidelines for NSSI: a quasi-experimental trial.

BACKGROUND: Non-suicidal self-injury (NSSI) is of high clinical relevance due to its high prevalence and negative long-term implications. In 2016, the German consensus-based clinical guidelines for diagnostic, assessment and treatment of NSSI in childhood and adolescence were published. However, research indicates that clinical guidelines are often poorly implemented in clinical practice. One crucial part of this process is the training of healthcare professionals to transfer knowledge and capacities to bring guideline recommendations into clinical practice. METHODS: The effect of three different dissemination strategies (printed educational material, e-learning, and blended-learning) on the NSSI guidelines´ recommendations was examined among 671 physicians and psychotherapists via an online-survey. The quasi-experimental study included three measurement points (before the training, after the training, 3-month follow-up) and mixed effects models were used to test for changes in knowledge, competences and attitudes toward NSSI and treatment. Moreover, the transfer of gained competences to practical work and user satisfaction were reviewed. RESULTS: With all three training formats, the intended changes of the outcome variables could be observed. Hereby, the printed educational material condition showed the lowest improvement in the scores for the 'negative attitudes toward NSSI and those who self-injure'. The training effect remained stable throughout the follow-up measurement. The highest application rate of acquired intervention techniques in clinical practice was reported for the blended-learning condition. For all three training strategies, user satisfaction was high and evaluation of training quality was positive, with printed educational material receiving the lowest and blended-learning the highest evaluations. CONCLUSIONS: In summary, all three training formats were perceived to be of high quality and seem to be suited to cover the needs of a heterogeneous group of physicians and psychotherapists. The choice of training method could be driven by considering which training goals are desired to be achieved and by the benefit-cost ratio allowing for tailored training approaches.

Endocannabinoid system reactivity during stress processing in healthy humans.

Stress underlies the development of various psychiatric disorders. Rodent studies suggest an involvement of the endocannabinoid system in the modulation of the stress response, which needs to be translated to humans. In this study, 22 healthy males (mean age: M = 22.7 years) were exposed to a thermal heat stressor in a fear conditioning paradigm and blood samples of the circulating endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were assessed. Additionally, electrodermal activity (EDA), task-related anxiety ratings and data on critical life experiences (CLE) were recorded. Interestingly, increases in 2-AG from pre-to-post stress correlated with: smaller stress responses (EDA), by trend more CLE, and greater conditioned anxiety. Smaller stress responses correlated with more CLE. We demonstrate a relation between endocannabinoid level changes from pre-to-post acute stress and the stress response. Our results suggest that investigating the role of 2-AG in the response to stress could be promising in finding treatments in the immediate aftermath of traumatic events.

Fear extinction learning and anandamide: an fMRI study in healthy humans.

Anxiety- and trauma-related disorders are severe illnesses with high prevalence. Current treatment options leave room for improvement and the endocannabinoid system (ECS) has become a key target in psychopharmacological research. Rodent models suggest an anxiolytic effect of endocannabinoids and demonstrated that the ECS is involved in the modulation of fear learning and aversive memory consolidation. So far, one prominent target was inhibition of fatty acid amino hydrolase (FAAH), the degrading enzyme of the endocannabinoid anandamide (AEA). Research in humans remains scarce, but genetic studies have found that the single-nucleotide polymorphism (SNP) FAAH C385A (rs324420) is associated with lower catabolic performance of FAAH and increased levels of AEA. Translational research on the ECS in fear learning processes is rare, yet crucial to understand the mechanisms involved. To address this lack of research, we designed a fear conditioning, extinction learning paradigm with 51 healthy, male humans who underwent functional magnetic resonance imaging (fMRI) before analysing baseline and task-related changes of AEA, as well as the FAAH polymorphism (rs324420). The results indicate higher AEA levels in AC-heterozygotes than in CC-individuals (SNP rs324420), but no difference between the groups during extinction learning. However, neural activation of the anterior cingulate cortex and anterior insular cortex during extinction learning correlated positively with AEA baseline levels, and task-related changes in AEA were found particularly during fear extinction, with a modulatory effect on neural activation related to extinction learning. Results indicate a putative role for AEA in fear extinction learning. Pre-treatment with AEA-enhancing drugs could promote extinction learning during psychotherapeutic interventions.

Correlations of the "Work-Family Conflict" With Occupational Stress-A Cross-Sectional Study Among University Employees.

Background: The working conditions at universities and hospitals are reported to be stressful. Several national and international studies have investigated occupational stress in hospitals. However, scientific studies at colleges and universities addressing psycho-social stress factors and their potential consequences are scarce. In this context, the consequences and correlations of the factor of work-family conflict, in particular, are currently uninvestigated. The aim of our study was to assess data on psychosocial stress in the context of the compatibility of work and family. Methods: Data were gathered through a cross-sectional-study, N = 844 (55% female, 41% male), on university staff (42.3% scientists, 14.3% physicians, 19.4% employees in administration, and 19.3% employees in service). Participants filled out questionnaires to provide their personal data and details of their work and private life conditions. For this purpose, we used the Work-Family and Family-Work Conflict Scales, Effort-Reward Inventory and Overcommitment Scale (ERI, OC), Patient Health Questionnaire (PHQ-4), short-form Maslach Burnout Inventory (MBI), and questions on their subjective health. Statistical analyses were performed using SPSS 22. Results: We found high levels of stress parameters in the total sample: extra work (83%), fixed-term work contracts (53%), overcommitment (OC, 26%), Effort-Reward Imbalance (18%, ERI Ratio > cut-off 0.715), work-family conflict (WFC, 35%), and family-work conflict (FWC, 39%). As hypothesized, we found significant correlations of both WFC and FWC with psychosocial work strain (ERI Ratio) as well as overcommitment (OC). Mental and somatic health parameters also had a significant positive correlation with WFC and FWC. Using a regression analysis (N = 844), we identified WFC as a predictor of burnout, while emotional exhaustion, extra work, and overcommitment could be identified as predictors of WFC and FWC. Discussion: The results of our study point toward deficits in the compatibility of work life and private life in the work fields of science, colleges, and universities. Furthermore, we found indicators that work-family conflicts (interrole conflicts) have an impact on mental and somatic health. These work-family conflicts should be targets for preventions and interventions with the aim of improving the work-life balance and mental and somatic wellbeing of employees.

Choosing a Surgical Access Point for Hysterectomy: A Paradigm Shift Over a 10-Year Span.

Background: When choosing a surgical procedure for a hysterectomy, doctors and patients have various options in terms of the multiple surgical access points available. The aim of this study was to descriptively analyze developments concerning the surgical access point selected over the past 10 years at Ulm University Hospital, (south) Germany, assess the variables associated with the surgical method and explore any potential significant correlations that influence these surgical access routes. Explicitly, we wished to investigate whether the approval of ulipristal acetate and the warning issued by the Food and Drug Administration (FDA) in connection with its use changed existing trends. Material and Methods: This monocentric study retrospectively assessed data from all patients who underwent a hysterectomy due to a benign disease or endometrial cancer from January 2007 until December 2016. Results: Of the benign indications considered, myomas and descensus genitalis occurred most frequently (49.5 and 30.6%, respectively). The percentage of abdominal procedures declined from 61.4 to 13.4% between 2007 and 2016 for all hysterectomies, whilst it increased from 4.1 to 69.7% for laparoscopic hysterectomies. The rate of vaginal hysterectomies increased to 45.5% until 2013 and declined in the years afterwards. Laparoscopic assisted vaginal hysterectomies were comparatively rare. The trends in terms of surgical routes were similar for endometrial cancer. During the observation period, the share of abdominal hysterectomies fell from 100 to 11.3%, whilst the share of laparoscopic hysterectomies increased from 0 to 86.6%. The other two procedures were less frequently used. Use of the laparoscopic hysterectomy procedure also increased significantly after the FDA's 2014 warning. Ulipristal acetate may have tended to influence the process. Conclusion: Contrary to the national decrease in hysterectomy numbers, the annual number of hysterectomies at Ulm University Hospital remained stable during the observation period. Nevertheless, there was a clear shift in the preferred surgical routes for hysterectomy.

Repeated fMRI in measuring the activation of the amygdala without habituation when viewing faces displaying negative emotions.

Functional imaging studies of affective disorders have demonstrated abnormal activity in the amygdala in response to emotionally salient stimuli. Since in other studies this response has been shown to habituate during the scanning session, it is not clear if it may be of use in monitoring disease progression or remission, or in monitoring the effects of therapy, as habituation may confound normalisation of response. We investigated here amygdala activation in healthy participants exposed to displays of emotional facial expressions in a sample of N = 31 individuals assessed twice in an interval of three weeks. At this interval no habituation could be detected, suggesting the validity of this imaging assay in repeated assessments of amygdalar reactivity. However, the fusiform gyrus and the inferior frontal lobes showed decreases in activations that may be related to the role of these areas in encoding visual and emotional aspects of the stimuli.

The iconography of mourning and its neural correlates: a functional neuroimaging study.

The present functional neuroimaging study focuses on the iconography of mourning. A culture-specific pattern of body postures of mourning individuals, mostly suggesting withdrawal, emerged from a survey of visual material. When used in different combinations in stylized drawings in our neuroimaging study, this material activated cortical areas commonly seen in studies of social cognition (temporo-parietal junction, superior temporal gyrus, and inferior temporal lobe), empathy for pain (somatosensory cortex), and loss (precuneus, middle/posterior cingular gyrus). This pattern of activation developed over time. While in the early phases of exposure lower association areas, such as the extrastriate body area, were active, in the late phases activation in parietal and temporal association areas and the prefrontal cortex was more prominent. These findings are consistent with the conventional and contextual character of iconographic material, and further differentiate it from emotionally negatively valenced and high-arousing stimuli. In future studies, this neuroimaging assay may be useful in characterizing interpretive appraisal of material of negative emotional valence.