Asenapine in the management of impulsivity and aggressiveness in bipolar disorder and comorbid borderline personality disorder: an open-label uncontrolled study

Borderline personality disorder (BPD) often co-occurres with bipolar disorder (BD). Impulsivity and aggressiveness represent core shared features and their pharmacological management is mainly based on mood stabilizers and antipsychotics, although scarce evidence is available for this context of comorbidity. The aim of the present study was to evaluate the role of Asenapine as an adjunctive drug for reducing aggressiveness and impulsivity in a sample of Italian BD type I outpatients with or without a comorbid BPD. This was an observational 12-week open-label uncontrolled clinical study carried out from April to October 2014 in two psychiatric clinics in Sicily. Each patient was treated with asenapine at two dose options, 5\u2009mg (twice daily) or 10\u2009mg (twice daily), and concomitant ongoing medications were not discontinued. We measured impulsivity using the Barratt Impulsiveness Scale (BIS) and aggressiveness using the Aggressive Questionnaire (AQ). For the analysis of our outcomes, patients were divided into two groups: with or without comorbid BPD. Adjunctive therapy was associated with a significant decrease of BIS and AQ overall scores in the entire bipolar sample. Yet, there was no significant difference in BIS and AQ reductions between subgroups. Using a regression model, we observed that concomitant BPD played a negative role on the Hostility subscale and overall AQ score variations; otherwise, borderline co-diagnosis was related positively to the reduction of physical aggression. According to our post-hoc analysis, global aggressiveness scores are less prone to decrease in patients with a dual diagnosis, whereas physical aggressiveness appears to be more responsive to the add-on therapy in patients with comorbidity

Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder

Introduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence. Methods: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland–Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis. Results: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [−8.1%, 16.74%]; no subgroup differences χ(2) = 1.24, p-value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [−0.87, 1.04]; χ(2) = 0.02, p-value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used. Discussion: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed

Exploration of mood spectrum symptoms during a major depressive episode: The impact of contrapolarity-Results from a transdiagnostic cluster analysis on an Italian sample of unipolar and bipolar patients

Background Subthreshold hypomania during a major depressive episode challenges the bipolar-unipolar dichotomy. In our study we employed a cross-diagnostic cluster analysis - to identify distinct subgroups within a cohort of depressed patients. Methods A k-means cluster analysis- based on the domain scores of the Mood Spectrum Self-Report (MOODS-SR) questionnaire-was performed on a data set of 300 adults with either bipolar or unipolar depression. After identifying groups, between-clusters comparisons were conducted on MOODS-SR domains and factors and on a set of sociodemographic, clinical and psychometric variables. Results Three clusters were identified: one with intermediate depressive and poor manic symptomatology (Mild), one with severe depressive and poor manic symptomatology (Moderate), and a third one with severe depressive and intermediate manic symptomatology (Mixed). Across the clusters, bipolar patients were significantly less represented in the Mild one, while the DSM-5 "Mixed features" specifier did not differentiate the groups. When compared to the other patients, those of Mixed cluster exhibited a stronger association with most of the illness-severity, quality of life, and outcomes measures considered. After performing pairwise comparisons significant differences between "Mixed" and "Moderate" clusters were restricted to: current and disease-onset age, psychotic ideation, suicidal attempts, hospitalization numbers, impulsivity levels and comorbidity for Cluster B personality disorder. Conclusions In the present study, a clustering approach based on a spectrum exploration of mood symptomatology led to the identification of three transdiagnostic groups of patients. Consistent with our hypothesis, the magnitude of subthreshold (hypo)manic symptoms was related to a greater clinical severity, regardless of the main categorical diagnosis

Molecular and clinical studies in five index cases with novel mutations in the GLA gene

Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21–22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in positions 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639 + 5 G > T) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects > 2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives clinicians an important support for the proper diagnosis of the disease

The international platform of registered systematic review and meta-analysis protocols (INPLASY) at 3 years: an analysis of 4,658 registered protocols on inplasy.com, platform features, and website statistics

Background: INPLASY® is an international platform for registering systematic reviews and meta-analysis protocols that was launched in March 2020. INPLASY® provides an online database in which the protocols are maintained as permanent public records and can be accessed on its website (www.inplasy.com). Methods: We described the database features and registered information of all records published since the launch of the registry on March 31, 2023. Additionally, we analyzed the website statistics dataset to explore user experience and promote data transparency. Results: Four thousand six hundred fifty-eight records were registered in INPLASY®, and more than 94% of the protocols were published within 24 h. Most of the submissions were from China, followed by Portugal, Taiwan, Malaysia, and Brazil. The INPLASY® website received 386,395 page views from 64,568 visitors during the first three years. The accesses were obtained from 170 countries. Most of the accesses were from China, followed by the US, the UK, and Portugal. The review status “completed and published” was observed in 898 protocols, and these studies were published in 372 different scientific peer-reviewed journals. The features of INPLASY® include the following: (i) INPLASY® identifier, a unique protocol number; (ii) the digital object identifier (DOI) number, the URL of the protocol linked to a specific DOI; (iii) ORCID update, INPLASY® automatically updates authors' ORCID page, including their protocol; and (iv) search tools, the protocols are freely accessible on www.inplasy.com. Conclusions: INPLASY® has several practical and useful features that should be considered when planning the registration of a systematic review protocol. Furthermore, the sharp increase in the number of protocols registered in INPLASY® in the first three years and the database statistics demonstrate that INPLASY® has become an important source of systematic review protocols. Therefore, authors should access INPLASY® before planning a future review study to avoid unintended duplication of efforts and to obtain timely registration.publishedVersio

Reflective functioning and dissociative experiences: A comparison study between adolescents at “high-risk” of psychosis and healthy controls

# Background Despite the established contribution to psychological well-being in young subjects, the investigation of reflective functioning and dissociative experiences in help-seekers adolescents still appears an unmet need. # Objective The study aimed to assess reflective functioning and dissociative symptoms in help-seekers adolescents, and compare them to gender-matched healthy controls. # Methods The Reflecting Functioning Questionnaire (RFQ) was used to investigate mentalizing; the Adolescent Dissociative Experience Scale (A-DES) was used to explore dissociative symptoms. # Results The study involved 102 adolescents (mean age 18.06 ± 1.78 years), split into "help-seekers" (N= 51; mean age 19 ± 1.98 years) and healthy controls (N= 51; mean age 17.12 ± 0.84). "Help-seekers" adolescents showed lower RFQ-certainty scores (mean 3.39 ± 2.47), compared to healthy controls (mean 6.73 ± 5.01). Furthermore, "help-seekers" adolescents reported higher scores on RFQ-uncertainty (mean 7.73 ± 4.38), compared to healthy controls (mean 5.14 ± 4.17), which indicates a greater lack of knowledge about mental states (hypomentalizing). Eventually, "help-seekers" adolescents showed significantly worse dissociative symptoms (A-DES total mean score 3.49 ± 2.04), compared to healthy controls (A-DES total mean score 2.06 ± 1.43). # Conclusion The importance of an assessment in early adolescence denotes a topic of increasing concern, in order to identify failures in reflective functioning and the onset of dissociative experiences among help-seekers adolescents, toward the implementation of tailored psychological interventions

Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed thatHsp60Fclassically a mitochondrial proteinFwas abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease

Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. Results. Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Pan- eth cells. IL-92positive mononuclear cells were demon- strated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimula- tion of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of a-defensin 5 and IL-23p19. Peripheral and synovial expansion of a4b71 Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. Conclusion. Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA