Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells

Omalizumab (OmAb) is a humanized anti-IgE antibody approved for the treatment of chronic spontaneous urticaria (CSU). OmAb's mechanism of action is known to include actions on free IgE and on pre-bound IgE. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria where IgE involvement is not clear, suggesting the involvement of additional mechanisms of action. In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera from CSU patients. For this purpose, we performed a comparison between the in vitro incubation of sera from CSU patients treated with OmAb and the in vivo administration of OmAb in a clinical trial. We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation. Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. Thus, we conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation

Neural response to the observable self in social anxiety disorder

The fulltext of this publication will be made publicly available after relevant embargo periods have lapsed and associated copyright clearances obtained.BACKGROUND: Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others. Method Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping. RESULTS: Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range. CONCLUSIONS: Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases

Chronic inflammation in hepatitis C patients is associated with increased perceived stress and abnormal connectivity between insula and basal ganglia

Background: Sickness Behavior(SB) is an organized adaptive strategy to support the organism's defense against pathogens [1]. Nevertheless,when the pathogen cannot be removed and is persistent,SB may become prolonged and dysfunctional,as in chronic hepatitis C(CHC) [2].The presence of chronic inflammation,beside vulnerability factors,seems to be crucial for the development of major depressive disorder(MDD),while impacting neuroimmune circuits or oxidative and nitrosative(O&NS) pathways [3]. Neuroimaging studies have pointed out the role of brain structures relevant to the SB,helping to identify those areas sensitive to peripheral inflammation such as basal ganglia or insula [4,5]. Aim: To elucidate clinical and neurobiological aspects of inflammation in CHC patients without current MDD diagnosis. Methods: Case-control study compared 35 CHC patients with 30 healthy controls,age(18-52 years old) and sex matched.Exclusion criteria were any active inflammatory condition,current anti-inflammatory treatment and MDD diagnosis(DSM-IV,MINI assessment).Physical health questionnaire for depression(PHQ-9) and perceived stress scale(PSS) were used for clinical assessment. Serum levels(sl) of inflammatory markers interleukin-6(IL-6) and prostaglandin-E2(PGE2), oxidative stress marker malonyl-dialdehyde(MDA) and anti-oxidant enzymes superoxide-dismutase(SOD) and catalase(CAT) were measured.Resting-state functional MRI(fMRI) was used to assess the changes in intrinsic brain networks in all participants. Functional connectivity maps were generated for a priori selected regions-of-interest(ROIs), including the bilateral insula, subgenual anterior cingulate(sgACC) cortex and bilateral putamen. Voxel-wise analyses in SPM served to assess the association between functional connectivity and clinical/biological variables. Results: Table 1 shows sociodemographics, biological markers and clinical characteristics of both samples. CHC patients showed increased PSS and PHQ-9 scores, IL-6 and PGE2 sl, and antioxidant system activation compared to controls. Subtle case-control differences in functional connectivity were also observed with patients showing decreased connectivity between insula and cingulate cortex, caudate nucleus and anterior prefrontal cortex; between sgACC and orbitofrontal cortex; between putamen, thalamus and temporal regions. By contrast, patients showed increased connectivity between insula and temporal cortex; sgACC and precuneus and temporal cortex; putamen, supramarginal gyrus and postcentral cortex. PHQ-9 and PSS scores were positive correlated only with PGE2 sl(r = 0.298, p = 0.019 and r = 0.245, p = 0.055 respectively).Interestingly, PSS and PHQ-9 scores were positively associated with connectivity between putamen and insula(peak correlation at MNI x = 32,y = 20,z = −20; cluster size = 11.9 ml; T = 4.8, p<0.0001; and x = 44,y = −8,z = −4;cluster size = 2.9 ml; T = 5.0, p<0.0001,respectively). PGE2 was also correlated with functional connectivity between putamen and insula (peak correlation at MNI x = 28,y = −6,z = 6; cluster size = 9.6 ml; T = 3.5, p<0.0001). Nevertheless, PGE2 did not mediate the correlation between PSS nor PHQ-9 and connectivity (t = 1.47,p = 0.141 and t = 1.37,p = 0.171,respectively). Conclusions: Patients with CHC exhibited increased perceived stress and depressive symptoms,which were associated with inflammatory markers together with alterations in connectivity between the insula to putamen,areas involved in interoceptive integration,emotional awareness, and orientation of motivational state. The absence of MDD in the study sample may explain the lack of oxidative stress in CHC patients

New evidence of heterogeneity in social anxiety disorder: defining two qualitatively different personality profiles taking into account clinical, environmental and genetic factors

Item does not contain fulltextPURPOSE: To study qualitatively different subgroups of social anxiety disorder (SAD) based on harm avoidance (HA) and novelty seeking (NS) dimensions. METHOD: One hundred and forty-two university students with SAD (SCID-DSM-IV) were included in the study. The temperament dimensions HA and NS from the Cloninger's Temperament and Character Inventory were subjected to cluster analysis to identify meaningful subgroups. The identified subgroups were compared for sociodemographics, SAD severity, substance use, history of suicide and self-harm attempts, early life events, and two serotonin transporter gene polymorphisms (5-HTTLPR and STin2.VNTR). RESULTS: Two subgroups of SAD were identified by cluster analysis: a larger (61% of the sample) inhibited subgroup of subjects with "high-HA/low-NS", and a smaller (39%) atypical impulsive subgroup with high-moderate HA and NS. The two groups did not differ in social anxiety severity, but did differ in history of lifetime impulsive-related-problems. History of suicide attempts and self-harm were as twice as frequent in the impulsive subgroup. Significant differences were observed in the pattern of substance misuse. Whereas subjects in the inhibited subgroup showed a greater use of alcohol (P=0.002), subjects in the impulsive subgroup showed a greater use of substances with a high-sensation-seeking profile (P<0.001). The STin2.VNTR genotype frequency showed an inverse distribution between subgroups (P=0.005). CONCLUSIONS: Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors

Neurotoxicity and depression symptomatology changes in patients with chronic hepatitis C after viral cure with direct-acting antivirals

International audienc

Depression prevalence using the HADS-D compared to SCID major depression classification: An individual participant data meta-analysis

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods: We searched Medline, Medline In-Process &amp; Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview. © 2020 Elsevier Inc

Probability of major depression diagnostic classification based on the SCID, CIDI and MINI diagnostic interviews controlling for Hospital Anxiety and Depression Scale – Depression subscale scores: An individual participant data meta-analysis of 73 primary studies

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores. Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)). Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity. © 2019 Elsevier Inc