Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model.

Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The landmark meta-analysis of functional neuroimaging studies by Etkin and Wager (2007) revealed primarily the typical fear circuit as overactive in SAD. Since then, new methodological developments such as functional connectivity and more standardized structural analyses of grey and white matter have been developed. We provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD since 2007 and present a new model of the neurobiology of SAD. We confirmed the hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and prefrontal cortex) in SAD. In addition, task-related functional studies revealed hyperactivation of medial parietal and occipital regions (posterior cingulate, precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic and executive network regions. Based on the result of this meta-analysis and review, we present an updated model of SAD adopting a network-based perspective. The disconnection of the medial parietal hub in SAD extends current frameworks for future research in anxiety disorders.This is the author's accepted manuscript. The final version is printed by Elsevier in Neuroscience & Biobehavioral Reviews here: http://www.sciencedirect.com/science/article/pii/S0149763414002012

SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli

Introduction: The prediction of antidepressant treatment response may improve outcome. Functional magnetic resonance imaging (fMRI) of emotion processing in major depressive disorder (MDD) may reveal regional brain function serving as predictors of response to treatment with selective serotonin reuptake inhibitor (SSRI). Methods: We examined the association between pre-treatment neural activity by means of fMRI during the perception of emotional stimuli in 22 patients with MDD and the treatment outcome after 6 weeks' medication with an SSRI. A whole brain correlation analysis with Beck Depression Inventory (BDI) change between pre- to post-treatment was conducted to identify neural regions associated with treatment response. Results: During the perception of positive stimuli, responders were characterized by more activation in posterior cingulate cortex (PCC), medial prefrontal cortex, and thalamus as well as middle temporal gyrus. During perception of negative stimuli, PCC, and pregenual anterior cingulate cortex showed the highest correlation with treatment response. Furthermore, responders exhibited higher activation to emotional stimuli than to neutral stimuli in all the above-mentioned regions, while non-responders demonstrated an attenuated neural response to emotional compared to neutral stimuli. Conclusion: Our data suggest that the activity of distinct brain regions is correlated with SSRI treatment outcome and may serve as treatment response predictor. While some regions, in which activity was correlated with treatment response, can be assigned to networks that have been implied in the pathophysiology of depression, most of our regions of interest could also be matched to the default mode network (DMN). Higher DMN activity has been associated with increased rumination as well as negative self-referential processing in previous studies. This may suggest our responders to SSRI to be characterized by such dysregulations and that SSRIs might modify the function associated with this network

When Non-Suicidal Self-Injury Predicts Non-Suicidal Self-Injury and Poor Sleep—Results from a Larger Cross-Sectional and Quasi-Longitudinal Study

Poor sleep is associated with a higher risk of non-suicidal self-injury (NSSI) as a proxy of unfavorable emotion regulation. In the present study, we tested the hypothesis that past non-suicidal self-injury was associated with current non-suicidal self-injury and with current subjective sleep patterns. To this end, a larger sample of young adults were assessed. A total of 2374 adults (mean age: 27.58 years; 39.6% females) completed a series of self-rating questionnaires covering sociodemographic information, past and current NSSIs, suicide attempts, and current sleep patterns, including experiencing nightmares. Past NSSIs predicted current NSSIs. Current sleep patterns had a modest impact on the association between past and current NSSIs. Compared to male participants, female participants did not report more sleep complaints or more current NSSIs, but more past NSSIs. Past NSSIs predicted the occurrences of nightmares and suicide attempts. The best predictor of current NSSI was the remembered past NSSI, while current poor sleep was only modestly associated with current NSSI. Further indicators of current NSSI and poor sleep were suicide attempts and nightmares within the last six months. Overall, it appears that poor emotion regulation should be considered as underlying factor to trigger and maintain non-suicidal self-injury-related behavior and poor sleep. Further, unlike previous studies, which focused on the possible influence of sleep patterns on NSSIs, the aim of the present study paradigm was to investigate NSSIs on sleep patterns

A Comprehensive Review on the Role of Non-Coding RNAs in the Pathophysiology of Bipolar Disorder

Aim: Bipolar disorder is a multifactorial disorder being linked with dysregulation of several genes. Among the recently acknowledged factors in the pathophysiology of bipolar disorder are non-coding RNAs (ncRNAs). Methods: We searched PubMed and Google Scholar databases to find studies that assessed the expression profile of miRNAs, lncRNAs and circRNAs in bipolar disorder. Results: Dysregulated ncRNAs in bipolar patients have been enriched in several neuron-related pathways such as GABAergic and glutamatergic synapses, morphine addiction pathway and redox modulation. Conclusion: Altered expression of these transcripts in bipolar disorder provides clues for identification of the pathogenesis of this disorder and design of targeted therapies for the treatment of patients. Keywords: bipolar disorder; circRNA; lncRNA; miRNA

Sleep Problems, Social Anxiety and Stuttering Severity in Adults Who Do and Adults Who Do Not Stutter

Background: While there is sufficient evidence that children and adolescents who stutter reported more impaired sleep compared to children and adolescents who did not stutter, findings among adults who stutter (AWS) were scarce. Furthermore, stuttering is associated with issues related to verbal communication in a social context. As such, it was conceivable that AWS reported higher scores for social anxiety, compared to adults who do not stutter (AWNS). In the present study, we tested whether AWS reported higher sleep complaints compared to AWNS. We further tested whether scores for social anxiety and stuttering independently predicted sleep disturbances. Methods: A total of 110 AWS (mean age; 28.25 years, 27.30% females) and 162 AWNS (mean age; 29.40 years, 51.20% females) completed a series of self-rating questionnaires covering sociodemographic information, sleep disturbances and social anxiety. Adults with stuttering further completed a questionnaire on stuttering. Results: Compared to AWNS, AWS reported a shorter sleep duration, a lower sleep efficiency, higher scores for drug use in terms of sleep-promoting medications (significant p-values and medium effect sizes), and an overall higher PSQI score (significant p-values and large effect size), when controlling for age and social anxiety. Next, while p-values were always significant for subjective sleep quality, sleep disturbances, and daytime functioning, when controlling for age and social anxiety, their effect sizes were trivial or small. For sleep latency, the p-value was not significant and the effect size was trivial. Among AWS, higher scores for stuttering and older age, but not social anxiety, predicted higher sleep disturbances. The association between higher sleep disturbances and higher stuttering severity was greatest among those AWS with highest scores for social anxiety. Conclusions: When compared to AWNS, AWS self-reported higher sleep disturbances, which were associated with older age, and higher scores for stuttering severity, but not with social anxiety. Adults who stutter might be routinely asked for their sleep quality

Influence of Lisdexamfetamine Dimesylate on Early Ejaculation—Results from a Double-Blind Randomized Clinical Trial

Background: Among male sexual dysfunctions, erectile dysfunction and early ejaculation have the highest prevalence rates. Here, we tested the influence of lisdexamfetamine dimesylate (Vyas®) on early ejaculation. To this end, we performed a double-blind randomized clinical trial among males with early ejaculation. Methods: A total of 46 males with early ejaculation (mean age: 35.23 years) and in stable marital relationships with regular weekly penile–vaginal intercourse were randomly assigned either to the lisdexamfetamine dimesylate condition (30 mg) or to the placebo condition. Compounds were taken about six hours before intended penile–vaginal intercourse. At baseline and four weeks later at the end of the study, participants completed a series of self-rating questionnaires covering early ejaculation. Female partners also rated participants’ early ejaculation profile. Results: Compared to the placebo condition, dimensions of early ejaculation improved over time in the lisdexamfetamine condition, though improvements were also observed in the placebo condition. Conclusions: Among male adults in stable marital relationships with regular weekly penile–vaginal intercourse, lisdexamfetamine dimesylate improved dimensions of early ejaculation. Given that improvements were also observed in the placebo condition, psychological factors such as increased attention to early ejaculation and favorable expectations of the compound should be considered

Influence of modafinil on early ejaculation - Results from a double-blind randomized clinical trial

BACKGROUND For men, early ejaculation is a serious health concern. Here, we tested the influence of modafinil (Profinil®) on early ejaculation. To this end, we performed a double-blind randomized clinical trial among men with early ejaculation. METHODS A total of 46 men with early ejaculation (mean age: 37.35 years) and in stable marital relationships with regular weekly penile-vaginal intercourse were randomly assigned either to the modafinil (100 mg) or to the placebo condition. Compounds were taken about 4-6h before intended penile-vaginal intercourse. At baseline and four weeks later at the end of the study, participants completed a series of self-rating questionnaires covering early ejaculation. Female partners also rated their male partners' early ejaculation profile. RESULTS Dimensions of early ejaculation improved over time, but only so in the modafinil condition, while no improvements were observed in the placebo condition. CONCLUSIONS Among male adults in stable marital relationships with regular weekly penile-vaginal intercourse modafinil improved dimensions of early ejaculation, always compared to placebo. Given the strong effect of modafinil on cognitive-executive processes, it is conceivable, that modafinil acted both via physiological and cognitive-executive pathways

Agomelatine for depression in schizophrenia: A case-series

OBJECTIVES: Agomelatine, a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, is a new antidepressant and a potential therapeutic option for major depressive episodes and negative symptoms in persons with schizophrenia. We investigated such treatment outcomes with respect to antidepressant efficacy, safety, and tolerability. METHODS: We report a consecutive case series of seven patients with schizophrenia and comorbid major depressive symptoms who received agomelatine for a period of at least six weeks in addition to stable doses of antipsychotic agents. General psychopathology, positive, negative and depressive symptoms were assessed with standardized interviews. Relevant blood parameters were assessed. RESULTS: Depressive symptoms improved significantly. Positive symptoms remained stable, while negative symptoms and global psychopathology improved significantly. Agomelatine was well tolerated in most patients. CONCLUSIONS: Our findings provide initial evidence that agomelatine is safe and efficacious in treating depressive symptoms in patients with schizophrenia. Furthermore, agomelatine seems to be effective for the treatment of negative symptoms. Randomized controlled trials are necessary to confirm these first observations

Sources of Sleep Disturbances and Psychological Strain for Hospital Staff Working during the COVID-19 Pandemic

Hospital staff members reported increased stress-related workload when caring for inpatients with COVID-19 (“frontline hospital staff members”). Here, we tested if depression, anxiety, and stress were associated with poor sleep and lower general health, and if social support mediated these associations. Furthermore, we compared current insomnia scores and general health scores with normative data. A total of 321 full-time frontline hospital staff members (mean age: 36.86; 58% females) took part in the study during the COVID-19 pandemic. They completed a series of questionnaires covering demographic and work-related information, symptoms of depression, anxiety, stress, social support, self-efficacy, and symptoms of insomnia and general health. Higher symptoms of depression, anxiety, and stress were associated with higher symptoms of insomnia and lower general health. Higher scores of depression, anxiety, and stress directly predicted higher insomnia scores and lower general health scores, while the indirect effect of social support was modest. Compared to normative data, full-time frontline hospital staff members had a 3.14 higher chance to complain about insomnia and a significantly lower general health. Symptoms of insomnia and general health were unrelated to age, job experience, educational level, and gender. Given this background, it appears that the working context had a lower impact on individuals’ well-being compared to individual characteristics

Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis

Background and objective: Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of IL-8 (-251T/A) and IL-6 (-174G/C) and the risk of oral cancer (OC). Methods: PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg’s and Egger’s tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results. Results: Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between IL-8 (-251T/A) polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 (p = 0.78), 0.86 (p = 0.55), 0.78 (p = 0.37), 0.83 (p = 0.45), and 1.10 (p = 0.34), respectively. The pooled ORs IL-6 (-174G/C) polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 (p = 0.87), 1.17 (p = 0.82), 1.44 (p = 0.38), 1.28 (p = 0.61), and 0.96 (p = 0.93), respectively. There was no association between IL-8 (-251T/A) polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of IL-6 (-174G/C) polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association. Conclusions: The meta-analysis confirmed that there was no association between the polymorphisms of IL-6 (-174G/C) and IL-8 (-251T/A) and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of IL-6 (-174G/C) and the risk OC