The role of the peripheral and central adrenergic system in the construction of the subjective emotional experience of panic.

RATIONALE: Although the study of emotions can look back to over 100 years of research, it is unclear which information the brain uses to construct the subjective experience of an emotion. OBJECTIVE: In the current study, we assess the role of the peripheral and central adrenergic system in this respect. METHODS: Healthy volunteers underwent a double inhalation of 35% CO2, which is a well-validated procedure to induce an intense emotion, namely panic. In a randomized, cross-over design, 34 participants received either a ß1-blocker acting selectively in the peripheral nervous system (atenolol), a ß1-blocker acting in the peripheral and central nervous system (metoprolol), or a placebo before the CO2 inhalation. RESULTS: Heart rate and systolic blood pressure were reduced in both ß-blocker conditions compared to placebo, showing effective inhibition of the adrenergic tone. Nevertheless, the subjective experience of the induced panic was the same in all conditions, as measured by self-reported fear, discomfort, and panic symptom ratings. CONCLUSIONS: These results indicate that information from the peripheral and central adrenergic system does not play a major role in the construction of the subjective emotion.

Individualized, connectome-based, non-invasive stimulation of OCD deep-brain targets: A proof-of-concept.

Treatment-resistant obsessive-compulsive disorder (OCD) generally improves with deep-brain stimulation (DBS), thought to modulate neural activity at both the implantation site and in connected brain regions. However, its invasive nature, side-effects, and lack of customization, make non-invasive treatments preferable. Harnessing the established remote effects of cortical transcranial magnetic stimulation (TMS), connectivity-based approaches have emerged for depression that aim at influencing distant regions connected to the stimulation site. We here investigated whether effective OCD DBS targets (here subthalamic nucleus [STN] and nucleus accumbens [NAc]) could be modulated non-invasively with TMS. In a proof-of-concept study with nine healthy individuals, we used 7T magnetic resonance imaging (MRI) and probabilistic tractography to reconstruct the fiber tracts traversing manually segmented STN/NAc. Two TMS targets were individually selected based on the strength of their structural connectivity to either the STN, or both the STN and NAc. In a sham-controlled, within-subject cross-over design, TMS was administered over the personalized targets, located around the precentral and middle frontal gyrus. Resting-state functional 3T MRI was acquired before, and at 5 and 25 min after stimulation to investigate TMS-induced changes in the functional connectivity of the STN and NAc with other regions of the brain. Static and dynamic seed-to-voxel correlation analyses were conducted. TMS over both targets was able to modulate the functional connectivity of the STN and NAc, engaging both overlapping and distinct regions, and unfolding following different temporal dynamics. Given the relevance of the engaged connected regions to OCD pathology, we argue that a personalized, connectivity-based procedure is worth investigating as potential treatment for refractory OCD.

Enhanced sleep staging with artificial intelligence: a validation study of new software for sleep scoring.

Manual sleep staging (MSS) using polysomnography is a time-consuming task, requires significant training, and can lead to significant variability among scorers. STAGER is a software program based on machine learning algorithms that has been developed by Medibio Limited (Savage, MN, USA) to perform automatic sleep staging using only EEG signals from polysomnography. This study aimed to extensively investigate its agreement with MSS performed during clinical practice and by three additional expert sleep technicians. Forty consecutive polysomnographic recordings of patients referred to three US sleep clinics for sleep evaluation were retrospectively collected and analyzed. Three experienced technicians independently staged the recording using the electroencephalography, electromyography, and electrooculography signals according to the American Academy of Sleep Medicine guidelines. The staging initially performed during clinical practice was also considered. Several agreement statistics between the automatic sleep staging (ASS) and MSS, among the different MSSs, and their differences were calculated. Bootstrap resampling was used to calculate 95% confidence intervals and the statistical significance of the differences. STAGER's ASS was most comparable with, or statistically significantly better than the MSS, except for a partial reduction in the positive percent agreement in the wake stage. These promising results indicate that STAGER software can perform ASS of inpatient polysomnographic recordings accurately in comparison with MSS.

Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes.

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.

Eye movement desensitization and reprocessing (EMDR) therapy or supportive counseling prior to exposure therapy in patients with panic disorder: study protocol for a multicenter randomized controlled trial (IMPROVE).

BACKGROUND: Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness. METHODS: A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment. DISCUSSION: The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach. TRIAL REGISTRATION: ISRCTN-ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022-retrospectively registered. ISRCTN-ISRCTN29668369.

Network analysis in Gamma Knife capsulotomy for intractable obsessive-compulsive disorder.

Introduction: Gamma-knife Ventral Capsulotomy (GVC) has been suggested as an efficacious treatment for a subset of patients with treatment refractory obsessive compulsive disorder (OCD). Research question: The goal of this study was to investigate neural correlates of GVC and investigate the predictive value of white matter tracts that are known to be associated with clinical outcome to Deep Brain Stimulation (DBS). Material and methods: MR images of 8 treatment-refractory OCD patients with a minimum follow-up of 3-years who underwent GVC were used to correlate lesion characteristics with symptom improvement. This exploratory study investigated relations between differences in cortical grey matter structure and subcortical structures before and after GVC for responding and non-responding patients (n â€‹= â€‹6). Normative diffusion MRI- based tractography was used to determine networks associated with successful lesions. Results: The mean total Y-BOCS reduction was 19.6 after three years, resulting in a response rate of 63%.The strongest correlation with symptom improvement was found for a decrease of the left ventral diencephalon volume (r â€‹= â€‹-0.83, p â€‹= â€‹0.039). Discriminative tractography suggest streamlines connecting the prefrontal cortex with the subthalamic nucleus to be associated with clinical response. However, results could not be validated either implicating interpatient anatomical variability or reflecting the relative small sample size as a limitation. Discussion/Conclusion: Taken together, the present study highlights the efficacy of GVC in patients with treatment-refractory OCD. Our results are suggestive of GVC treatment efficacy being mediated by the involvement of a subpart of the ALIC connecting the PFC and the STN.

Anxiety and depression in small fiber neuropathy.

Psychiatric comorbidity is common in patients with chronic pain. In peripheral neuropathic pain, particularly anxiety and mood disorders are frequently present and associated with a high level of catastrophizing. Small fiber neuropathy (SFN) is a peripheral neuropathy dominated by pain. This study aimed to investigate the prevalence of and factors associated with anxiety and depressive symptoms in SFN. All consecutive patients diagnosed with SFN at Maastricht University Medical Center+, between September 2016 and October 2021, were included (n = 1310). Data on demographics, medical history, diagnostic tests, and questionnaires about pain, SFN-specific symptoms, and mental health were collected once. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression and the Pain Catastrophizing Scale (PCS) to measure the degree of catastrophizing. One-third of the patients had an abnormal HADS score (≥11) on the subscales anxiety and/or depression (26.5% anxiety and 23.0% depression) indicating clinical relevance. Regression analysis showed that higher pain intensity, catastrophizing, and more SFN-related complaints were significantly associated with an abnormal HADS-score. In conclusion, the prevalence of reported anxiety or depressive symptoms in SFN is 36.3%. A multidisciplinary approach, not only focusing on pain relief, is therefore essential for the treatment of SFN.

Abnormal white-matter rich-club organization in obsessive-compulsive disorder.

Rich-club organization is key to efficient global neuronal signaling and integration of information. Alterations interfere with higher-order cognitive processes, and are common to several psychiatric and neurological conditions. A few studies examining the structural connectome in obsessive-compulsive disorder (OCD) suggest lower efficiency of information transfer across the brain. However, it remains unclear whether this is due to alterations in rich-club organization. In the current study, the structural connectome of 28 unmedicated OCD patients, 8 of their unaffected siblings and 28 healthy controls was reconstructed by means of diffusion-weighted imaging and probabilistic tractography. Topological and weighted measures of rich-club organization and connectivity were computed, alongside global and nodal measures of network integration and segregation. The relationship between clinical scores and network properties was explored. Compared to healthy controls, OCD patients displayed significantly lower topological and weighted rich-club organization, allocating a smaller fraction of all connection weights to the rich-club core. Global clustering coefficient, local efficiency, and clustering of nonrich club nodes were significantly higher in OCD patients. Significant three-group differences emerged, with siblings displaying highest and lowest values in different measures. No significant correlation with any clinical score was found. Our results suggest weaker structural connectivity between rich-club nodes in OCD patients, possibly resulting in lower network integration in favor of higher network segregation. We highlight the need of looking at network-based alterations in brain organization and function when investigating the neurobiological basis of this disorder, and stimulate further research into potential familial protective factors against the development of OCD.

No Sex Differences in Self-Reported Childhood Maltreatment in Major Depressive and Bipolar Disorders: A Retrospective Study.

BACKGROUND: We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients' age on the CM self-report were investigated. METHODS: This retrospective study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). RESULTS: Three hundred thirty-five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between increasing patients' age and a decreasing burden of CM. CONCLUSION: Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support routine CM assessment in psychiatric clinical practice.

Home alone: Social functioning as a transdiagnostic marker of mental health in youth, exploring retrospective and daily life measurements.

PURPOSE: Early detection and intervention of mental health problems in youth are topical given that mental disorders often start early in life. Young people with emerging mental disorders however, often present with non-specific, fluctuating symptoms. Recent reports indicate a decline in social functioning (SF) as an early sign of specific emerging mental disorders such as depression or anxiety, making SF a favorable transdiagnostic approach for earlier detection and intervention. Our aim was to investigate the value of SF in relation to transdiagnostic symptoms, and as a predictor of psychopathology over time, while exploring traditional retrospective versus innovative daily diary measurements of SF in youth. METHOD: Participants (N = 75) were 16-25 years of age and presented early stage psychiatric symptomatology. Psychiatric symptoms, including anxiety and depression, as well as SF -both in retrospect and in daily life- were assessed at two time points and analyzed cross-sectionally and longitudinally. RESULTS: A significant and negative association between SF and all psychiatric symptoms was found, and SF was a significant predictor of change in general psychiatric symptoms over time. Results were only significant when SF was measured traditionally retrospective. CONCLUSION: This study confirms a distinct relation between SF and transdiagnostic psychiatric symptoms in youth, even in a (sub)clinical population, and points towards SF as a predictor of transdiagnostic psychiatric symptoms. Further research is needed to learn more about the added value of daily life versus retrospective measurements.

Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression.

Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

Methodological Considerations for Setting Up Deep Brain Stimulation Studies for New Indications.

Deep brain stimulation (DBS) is a neurosurgical treatment with a growing range of indications. The number of clinical studies is expanding because of DBS for new indications and efforts to improve DBS for existing indications. To date, various methods have been used to perform DBS studies. Designing a clinical intervention study with active implantable medical devices has specific challenges while expanding patient treatment. This paper provides an overview of the key aspects that are essential for setting up a DBS study.

Cognitive Outcome After Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: A Systematic Review.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects, and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). BACKGROUND: This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). MATERIALS AND METHODS: EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. RESULTS: Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular, cognitive flexibility. CONCLUSION: Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used precluded a meta-analysis to confirm its safety and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In the future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience.

INTRODUCTION: Although deep brain stimulation (DBS) is effective for treating a number of neurological and psychiatric indications, surgical and hardware-related adverse events (AEs) can occur that affect quality of life. This study aimed to give an overview of the nature and frequency of those AEs in our center and to describe the way they were managed. Furthermore, an attempt was made at identifying possible risk factors for AEs to inform possible future preventive measures. MATERIALS AND METHODS: Patients undergoing DBS-related procedures between January 2011 and July 2020 were retrospectively analyzed to inventory AEs. The mean follow-up time was 43 ± 31 months. Univariate logistic regression analysis was used to assess the predictive value of selected demographic and clinical variables. RESULTS: From January 2011 to July 2020, 508 DBS-related procedures were performed including 201 implantations of brain electrodes in 200 patients and 307 implantable pulse generator (IPG) replacements in 142 patients. Surgical or hardware-related AEs following initial implantation affected 40 of 200 patients (20%) and resolved without permanent sequelae in all instances. The most frequent AEs were surgical site infections (SSIs) (9.95%, 20/201) and wire tethering (2.49%, 5/201), followed by hardware failure (1.99%, 4/201), skin erosion (1.0%, 2/201), pain (0.5%, 1/201), lead migration (0.52%, 2/386 electrode sites), and hematoma (0.52%, 2/386 electrode sites). The overall rate of AEs for IPG replacement was 5.6% (17/305). No surgical, ie, staged or nonstaged, electrode fixation, or patient-related risk factors were identified for SSI or wire tethering. CONCLUSIONS: Major AEs including intracranial surgery-related AEs or AEs requiring surgical removal or revision of hardware are rare. In particular, aggressive treatment is required in SSIs involving multiple sites or when Staphylococcus aureus is identified. For future benchmarking, the development of a uniform reporting system for surgical and hardware-related AEs in DBS surgery would be useful.

Perceptual sensitivity to sensory and affective aspects of dyspnea: Test-retest reliability and effects of fear of suffocation.

Perceptual sensitivity for dyspnea (i.e. breathlessness) is often quantified using the slope of magnitude estimations plotted against the physical stimulus intensities of respiratory loads. This study investigated whether this slope and its stability varies as a function of (1) affective versus sensory aspects of dyspnea, and (2) interindividual differences in Fear of Suffocation. Eighty-three healthy women performed a load magnitude estimation task twice one week apart. Resistive loads of increasing magnitude (0-2.4-5-7.4-12.4-20 cmH20/l/s) were repeatedly presented for a single flow-targeted inspiration. One group rated the intensity of loads, another their unpleasantness. Neither slopes nor intercepts differed between sensory versus affective aspects of dyspnea. Intercepts were lower in the second compared to the first session. Fear of Suffocation was associated with flatter slopes. Test-retest reliabilities were low to moderate suggesting that perceptual sensitivity to dyspnea is less stable than commonly assumed.

Prediction of illness remission in patients with Obsessive-Compulsive Disorder with supervised machine learning.

INTRODUCTION: The course of OCD differs widely among OCD patients, varying from chronic symptoms to full remission. No tools for individual prediction of OCD remission are currently available. This study aimed to develop a machine learning algorithm to predict OCD remission after two years, using solely predictors easily accessible in the daily clinical routine. METHODS: Subjects were recruited in a longitudinal multi-center study (NOCDA). Gradient boosted decision trees were used as supervised machine learning technique. The training of the algorithm was performed with 227 predictors and 213 observations collected in a single clinical center. Hyper-parameter optimization was performed with cross-validation and a Bayesian optimization strategy. The predictive performance of the algorithm was subsequently tested in an independent sample of 215 observations collected in five different centers. Between-center differences were investigated with a bootstrap resampling approach. RESULTS: The average predictive performance of the algorithm in the test centers resulted in an AUROC of 0.7820, a sensitivity of 73.42%, and a specificity of 71.45%. Results also showed a significant between-center variation in the predictive performance. The most important predictors resulted related to OCD severity, OCD chronic course, use of psychotropic medications, and better global functioning. LIMITATIONS: All recruiting centers followed the same assessment protocol and are in The Netherlands. Moreover, the sample of the data recruited in some of the test centers was limited in size. DISCUSSION: The algorithm demonstrated a moderate average predictive performance, and future studies will focus on increasing the stability of the predictive performance across clinical settings.

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Efficacy of a transdiagnostic ecological momentary intervention for improving self-esteem (SELFIE) in youth exposed to childhood adversity: study protocol for a multi-center randomized controlled trial.

BACKGROUND: Targeting low self-esteem in youth exposed to childhood adversity is a promising strategy for preventing adult mental disorder, but psychological help remains difficult to access and accept for youth, calling for novel, youth-friendly approaches. Mobile Health (mHealth) and, most prominently, ecological momentary interventions (EMIs) provide a unique opportunity to deliver youth-friendly, personalized, real-time, guided self-help interventions. The aim of this study is to investigate the efficacy of a novel, accessible, transdiagnostic ecological momentary intervention for improving self-esteem ('SELFIE') in youth with prior exposure to childhood adversity. METHODS/DESIGN: In a parallel-group, assessor-blind, multi-center randomized controlled trial, individuals aged 12-26 years with prior exposure to childhood adversity and low self-esteem will be randomly allocated to SELFIE in addition to treatment as usual (TAU) as the experimental condition or the control condition of TAU only, which will include access to all standard health care. SELFIE is a digital guided self-help intervention administered through a smartphone-based app to allow for interactive, personalized, real-time and real-world transfer of intervention components in individuals' daily lives, blended with three training sessions delivered by trained mental health professionals over a 6-week period. Outcomes will be assessed at baseline, post-intervention, and 6-month follow-up by blinded assessors. The primary outcome will be the level of self-esteem as measured with the Rosenberg Self-Esteem Scale (RSES). DISCUSSION: The current study is the first to establish the efficacy of an EMI focusing on improving self-esteem transdiagnostically in youth exposed to childhood adversity. If this trial provides evidence on the efficacy of SELFIE, it has significant potential to contribute to minimizing the deleterious impact of childhood adversity and, thereby, preventing the development of mental disorder later in life. TRIAL REGISTRATION: Netherlands Trial Register NL7129 (NTR7475 ). Registered on 9 November 2018.

The effect of intranasally administered oxytocin on observed social behavior in social anxiety disorder.

Research has shown that patients with a social anxiety disorder (SAD) show social performance deficits. These deficits are a maintaining factor in SAD, as mending social behavior improves interpersonal judgments and reduces social anxiety. Thus finding ways to enhance social behavior is evidently of importance in the treatment of SAD. This double-blind, placebo-controlled study investigated the effect of an intranasal administration of the hormone oxytocin (24 IU) on social behavior and anxious appearance in SAD patients (N = 40) and healthy controls (N = 39). Forty minutes after oxytocin administration participants were submitted to two live social situations (i.e., a waiting room situation and a getting acquainted task). The participants ('self-rated') and observers ('observer-rated') scored participants' social behavior and anxious appearance. Participants also rated their positive and negative affect. Confirming the social performance deficits in SAD, observers regarded SAD patients as more anxious and less socially skilled than healthy controls. Results indicated oxytocin-induced improvement of observer-rated social behavior in SAD patients compared to placebo but only in the getting acquainted task. This effect was not perceived as such by patients themselves and did not improve their affect ratings. In conclusion, this study found support for the idea that oxytocin helps SAD patients to perform better in social interactions, although this improvement seemed context-dependent (i.e., only present in the getting-acquainted task) and 'not perceived by the patient.