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Ketamine is swiftly effective in a range of neurotic disorders that are resistant to conventional antidepressant and anxiolytic drugs. The neural basis for its therapeutic action is unknown. Here we report the effects of ketamine on the EEG of patients with treatment-resistant generalized anxiety and social anxiety disorders. Twelve patients with refractory DSM-IV generalized anxiety disorder and/or social anxiety disorder provided EEG during 10 minutes of relaxation before and 2 hours after receiving double-blind drug administration. Three ascending ketamine dose levels (0.25, 0.5, and 1 mg/kg) and midazolam (0.01 mg/kg) were given at 1-week intervals to each patient, with the midazolam counterbalanced in dosing position across patients. Anxiety was assessed pre- and postdose with the Fear Questionnaire and HAM-A. Ketamine dose-dependently improved Fear Questionnaire but not HAM-A scores, decreased EEG power most at low (delta) frequency, and increased it most at high (gamma) frequency. Only the decrease in medium-low (theta) frequency at right frontal sites predicted the effect of ketamine on the Fear Questionnaire. Ketamine produced no improvement in Higuchi's fractal dimension at any dose or systematic changes in frontal alpha asymmetry. Ketamine may achieve its effects on treatment-resistant generalized anxiety disorder and social anxiety disorder through related mechanisms to the common reduction by conventional anxiolytic drugs in right frontal theta. However, in the current study midazolam did not have such an effect, and it remains to be determined whether, unlike conventional anxiolytics, ketamine changes right frontal theta when it is effective in treatment-resistant depression.

Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin’s effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin’s anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.

Background There is growing evidence that Internet-based cognitive behavioral therapy (ICBT) is as effective as a stand-alone treatment and helps facilitating access to treatment. Given the complexity of the treatment, we argue that the effect of ICBT could be even greater if guided by a therapist, as this could increase treatment adherence. We modified an established and well-evaluated treatment approach and developed a mobile application for treating social anxiety disorder (SAD). In the present study, we compare the efficacy of app use alone (APP) with video-based, therapist-guided app use (TG-APP) and with a wait-list control group (WLC) in terms of symptom reduction, and various secondary outcomes such as increase in quality of life or decrease of general psychological distress. Methods/design A within-between interaction design with randomization to one of three conditions will be used. In the APP condition, patients receive only the app without any additional contact with therapists, while in the TG-APP condition, therapists provide 8 sessions of video-based treatment in addition to using the app. The study will be conducted in two university outpatient treatment centers with reliably diagnosed SAD patients. The primary outcome will be defined as change in SAD symptoms, as measured by the Liebowitz Social Anxiety Scale (expert rating). Furthermore, a wide range of self-reports and clinician ratings for other symptoms (depression, general psychopathology) or quality of life will be used. A simulation-based power analysis for a 3 × 2 interaction effect (group × time) on the primary outcome in a linear mixed model resulted in a total sample size of N = 165. Discussion The present study will be one of the first to examine the additional benefit of therapist-guided video sessions regarding the use of an app treating SAD. Study results are pivotal to future treatment application in SAD.

Social anxiety disorders are among the most prevalent anxiety disorders in the general population. The efficacy of cognitive behavioral therapy (CBT) for social anxiety disorders is well demonstrated. However, only three studies point to the efficacy of systemic therapy (ST) in anxiety disorders, and only two of them especially focus on social anxiety disorders. These ST studies either do not use a good comparator but minimal supportive therapy, they do not use a multi-person ST but a combined therapy, or they do not especially focus on social anxiety disorders but mood and anxiety disorders in general. Though ST was approved as evidence based in Germany for a variety of disorders in 2008, evidence did not include anxiety disorders. This is the first pilot study that will investigate multi-person ST, integrating a broad range of systemic methods, specifically for social anxiety disorders and that will compare ST to the \"gold standard\" CBT. This article describes the rationale and protocol of a prospective, open, interventive, balanced, bi-centric, pilot randomized controlled trial (RCT). A total of 32 patients with a primary SCID diagnosis of social anxiety disorder will be randomized to either CBT or ST. Both treatments will be manualized. The primary outcome will include social anxiety symptoms at the end of therapy. Therapy will be restricted to no more than 26 hours (primary endpoint). Secondary outcomes will include psychological, social systems and interpersonal functioning, symptom adjustment, and caregiver burden, in addition to change measures, therapist variables and treatment adherence. At the secondary endpoints, 9 and 12 months after the beginning of therapy, we will again assess all outcomes. The study is expected to pilot test a RCT which will be the first to directly compare CBT and multi-person ST, integrating a broad range of systemic methods, for social anxiety disorders, and it will provide empirical evidence for the calculation of the number of patients needed for a confirmatory RCT. ClinicalTrials.gov: NCT02360033 ; date of registration: 21 January 2015.

Social anxiety disorder is characterized by an intense fear of social situations in which a person anticipates being evaluated negatively. Preferred treatments include cognitive behavioral therapy and selective serotonin-reuptake inhibitors. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. Stage A 26-year-old student reports feeling very anxious when giving a presentation, taking an examination, or meeting an authority figure. In these situations, he has palpitations, tremors, blushing, and sweating, and he is fearful that he will embarrass himself. He reports having few social contacts and avoids going to parties and making phone calls, but he feels lonely. His anxieties started during his teenage years and have increased considerably since he started attending a university. How should this case be managed? The Clinical Problem Social anxiety disorder is characterized by an intense fear of social situations in which the person . . .

We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals’ treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.

Social fears arise when fearing to be judged in social events. When these fears are intense, persistent, and debilitating, the individual may suffer from social anxiety disorder (SAD), which has its most frequent onset during adolescence and tends to be chronic. Still, evidence on the prevalence of social fears and SAD in adolescence is scarce. This study analyzed the prevalence of social fears and of SAD in Portuguese adolescents. Of the initial sample (n = 1495), 26% presented with intense self-reported social fears. Of those, 53.9% accepted to be further assessed for diagnosis, resulting in a point-estimate prevalence of adolescent SAD of 9.4%; this is slightly higher than previously found. Social performance was the most feared social event. Of the adolescents with SAD, 12.9% were receiving psychological intervention, 12.1% refused intervention, and 92 (65.7%) accepted intervention. Findings confirm SAD as a highly prevalent mental disorder among adolescents, particularly girls, and additionally, that most of these adolescents did not seek treatment but are willing to receive help if made available. Hence, schools should be invested not only in identifying vulnerable adolescents but also in providing diverse intervention options, tailored to their needs, and directing them to successful developmental trajectories.

Understanding shared and unique constructs underlying social communication difficulties in autism spectrum disorder (ASD) and social anxiety disorder (SAD) can address potential diagnostic overshadowing when evaluating SAD in the context of autism. Using self-report measures, factor analyses examined constructs underlying autistic traits, social anxiety, internalising symptoms and wellbeing amongst 267 neurotypical (17–19 years) and 145 autistic (15–22 years) students in the UK. Shared constructs across measures assessed general social communication competency (e.g., social distress in new situations and peer relationships). Fear of Negative Evaluation (FNE) was identified in both samples as a stable construct unique to social anxiety. Adapting interventions targeting SAD in autism should target FNE during adolescence which marks a period of heightened peer interaction and social vulnerability.

Social anxiety disorder (SAD) is commonly comorbid with autism spectrum disorder (ASD). Here, in a sample of 86 children and adolescents ( M AGE  = 12.62 years; 68.6% male), 28 of whom were diagnosed with ASD, 34 with SAD, and 24 with comorbid ASD and SAD, we compared parent-reported scores from the Social Responsiveness Scale-Second Edition (SRS-2; Constantino and Gruber in Social Responsiveness Scale (SRS; Constantino and Gruber 2012 ) to determine the sensitivity and specificity of the measure in cases of differential diagnosis between SAD and ASD. Results suggest that neither the subscales, nor the SRS-2 total score, consistently differed between ASD and SAD. Sensitivity and specificity analyses suggested that the SRS-2 total poorly discriminated ASD from SAD. When screening socially anxious youth for possible ASD, caution should be taken.

Research in psychology demonstrates a strong link between state affect (moment-to-moment experiences of positive or negative emotionality) and trait affect (eg, relatively enduring depression and social anxiety symptoms), and a tendency to withdraw (eg, spending time at home). However, existing work is based almost exclusively on static, self-reported descriptions of emotions and behavior that limit generalizability. Despite adoption of increasingly sophisticated research designs and technology (eg, mobile sensing using a global positioning system [GPS]), little research has integrated these seemingly disparate forms of data to improve understanding of how emotional experiences in everyday life are associated with time spent at home, and whether this is influenced by depression or social anxiety symptoms. We hypothesized that more time spent at home would be associated with more negative and less positive affect. We recruited 72 undergraduate participants from a southeast university in the United States. We assessed depression and social anxiety symptoms using self-report instruments at baseline. An app (Sensus) installed on participants' personal mobile phones repeatedly collected in situ self-reported state affect and GPS location data for up to 2 weeks. Time spent at home was a proxy for social isolation. We tested separate models examining the relations between state affect and time spent at home, with levels of depression and social anxiety as moderators. Models differed only in the temporal links examined. One model focused on associations between changes in affect and time spent at home within short, 4-hour time windows. The other 3 models focused on associations between mean-level affect within a day and time spent at home (1) the same day, (2) the following day, and (3) the previous day. Overall, we obtained many of the expected main effects (although there were some null effects), in which higher social anxiety was associated with more time or greater likelihood of spending time at home, and more negative or less positive affect was linked to longer homestay. Interactions indicated that, among individuals higher in social anxiety, higher negative affect and lower positive affect within a day was associated with greater likelihood of spending time at home the following day. Results demonstrate the feasibility and utility of modeling the relationship between affect and homestay using fine-grained GPS data. Although these findings must be replicated in a larger study and with clinical samples, they suggest that integrating repeated state affect assessments in situ with continuous GPS data can increase understanding of how actual homestay is related to affect in everyday life and to symptoms of anxiety and depression.