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Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and noninvasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future. [ABSTRACT FROM AUTHOR]

• Three silylation reagents were evaluated for the GC analysis of vitamin D. • MS ionization of the silylated derivatives was performed at 20-eV EI energy. • Multiple reaction monitoring (MRM) transitions of 6 target analytes were optimized. • Fast GC-QqQ-MS method proved to be sensitive and selective for vitamin D assay. • Accuracy assessment was evaluated analyzing SRM 972a by NIST. The proposed research was focused on the development of a gas chromatography-tandem mass spectrometry (GC-QqQ-MS) method under milder electron ionization (EI) conditions for the assay of vitamin D metabolites in human serum. Efficiency of three different silylation agents was evaluated for the conversion of vitamin D species into trimethylsilyl (TMS) derivatives, among which N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) proved to be the most effective. Indeed, the MSTFA reagent was able to convert in TMS ether even the 25-hydroxyl vitamin D derivative that, as known, possesses steric hindrance problems. The separation of vitamin D compounds was obtained in about 11.5 min using a narrow-bore column of dimensions 30 m × 0.25 mm ID × 0.10 μm d f with a poly(5% diphenyl/95% dimethyl siloxane) stationary phase. The mass spectrometry ionization of the silylated derivatives was performed under milder EI conditions (20-eV energy) that, respect to common 70-eV energy, generated scan mass spectra with higher relative and absolute intensities of high-mass diagnostic ions, along with a reduced abundance of the low-mass. The signals of the ionized compounds were acquired in multi-reaction-monitoring (MRM) mode, thus enabling the obtainment of highly-sensitive and selective quantitative data. The developed method was validated in term of linearity, accuracy, limits of detection (LoD) and quantification (LoQ). In detail, regression coefficients of the calibration curves were between 0.9959 and 0.9999; LoDs ranged from 0.06 ng mL−1 to 0.73 ng mL−1 and LoQs from 0.16 ng mL−1 to 2.45 ng mL−1. With respect to accuracy, the serum SRM 972a certified reference material (Vitamin D metabolites in frozen human serum) (Levels 1–4) was analyzed. [ABSTRACT FROM AUTHOR]

Background. The 22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition at high risk of developing both psychosis and motor disorders. Social Cognition (SC) deficits have been associated not only with schizophrenia but also with Parkinson's disease (PD). The present study assessed SC deficits in 22q11.2DS and investigated the interaction between motor symptoms and deficits in Facial Emotion Expressions (FEE) recognition and in Theory of Mind (ToM) tasks in people with 22q11.2DS. Methods. We recruited 38 individuals with 22q11.2DS without psychosis (N = 38 , DEL) and 18 with 22q11.2DS and psychosis (N = 18 , DEL_SCZ). The Positive And Negative Syndrome Scale (PANSS), Ekman's 60 Faces Test (EK-60F), the Awareness of Social Inference Test (TASIT EmRec), and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (UPDRS III) were administered. Correlations were sought between UPDRS III and both TASIT EmRec and EK-60F scores. Analyses were conducted separately for each psychopathological subgroup. Results. Higher UPDRS III (p = 0.04) and lower EK-60F (p = 0.025) scores were observed in the DEL_SCZ group. We found inverse correlations between UPDRS III and both TASIT EmRec (r = − 0.289 , p = 0.031) and EK-60F (r = − 0.387 , p = 0.006) scores in the whole sample. Correlations were no longer significant in the DEL_SCZ group (UPDRS III-TASIT EmRec p = 0.629 ; UPDRS III-EK60F p = 0.933) whilst being stronger in the DEL group (TASIT EmRec, r = − 0.560 , p < 0.001 ; EK60F, r = − 0.542 , p < 0.001). Analyses were adjusted for CPZ Eq and IQ. Conclusions. A modulation between FEE recognition deficits and motor symptoms and signs was observed in the 22q11.2DS group, likely affecting patients' quality of life. [ABSTRACT FROM AUTHOR]

Despite entailing more severe and uncommon side effects in 22q11.2DS compared to idiopathic schizophrenia, we strongly believe that clozapine should continue to be considered the gold standard for all treatment‐resistant schizophrenia, even in 22qDS. [ABSTRACT FROM AUTHOR]

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view. By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat 'paradoxical' mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles. [ABSTRACT FROM AUTHOR]

Background: Social cognition (SC) deficits and of its facial emotion expression (FEE) component have been described in 22q11.2 Deletion Syndrome (22q11.2DS), a high-risk for schizophrenia (SCZ) systemic genetic syndrome. Correlations between deficits in FEE skills and visual-spatial abilities in people with 22q11.2DS warrant investigation., Methods: The sample consisted of 37 patients with 22q11.2DS (DEL), 19 with 22q11.2DS and psychosis (DEL-SCZ), 23 with idiopathic SCZ, and 48 healthy controls. We assessed FEE through The Ekman 60 Faces test (EK-F60), visual-spatial skills with Raven's Standard Progressive Matrices, and symptom severity with the positive And negative syndrome scale. Statistics were conducted through multivariate analysis of variance and correlation analysis., Results: Patients with 22q11.2DS performed worse that the other groups in recognizing Surprise, Disgust, Rage, Fear, and Neutral expressions on the EK-F60. Recognition of Surprise and Disgust correlated positively with visual-spatial abilities in patients with 22q11.2DS; negative and cognitive symptoms correlated negatively with recognition of Sadness, Surprise, and Disgust., Conclusions: Patients with 22q11.2DS show impairments of both peripheral and central steps of the emotional recognition process, leading to SC deficits. The latter are present regardless of the presence of a full-blown psychosis., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: The 22q11.2 Deletion Syndrome (22q11.2DS) is considered the most reliable biological model to study genetic vulnerability to schizophrenia. It appears useful to investigate neuroanatomical characteristics of people with 22q11.2DS compared to chronic schizophrenia and healthy controls., Methods: The sample consisted of 16 individuals with a diagnosis of schizophrenia for over 10 years (SCZ>10), 14 with a diagnosis for less than 10 years (SCZ≤10), 11 patients with 22q11.2DS with no diagnosis of psychotic disorder (DEL, n=11) and 19 healthy controls (HCs, n=19). Global intelligence (IQ) was evaluated for all subjects. Voxel-Based Morphometry (VBM) was employed to investigate potential differences between groups in grey matter volumes., Results: VBM located the most significant difference between SCZ and HCs in the left medial frontal gyrus, where SCZ>10 group showed a significant reduction of grey matter volume; the same cluster resulted significantly decreased in DEL group compared to HCs as well. Despite the extensive grey matter abnormalities observed in 22q11.2DS, the DEL group showed the only significant differences compared to the SCZ>10 group in the right lingual gyrus volumes., Conclusions: Despite the small sample, our study identified a common area of grey matter loss both in idiopathic schizophrenia and 22q11.2DS.

Background: 22q11.2 Deletion Syndrome (22q11DS) represents one of the most important genetic risk factors for schizophrenia (SCZ) and a reliable biological model to study endophenotypic characters of SCZ. The aim of the study was to investigate Social Cognition impairments in subjects with 22q11.2DS compared to a considerable sample of schizophrenic patients., Methods: Forty-four individuals with 22q11.2DS (DEL) and 18 patients with 22q11.2DS and psychosis (DEL&#95;SCZ) were enrolled; these groups were compared to 887 patients with schizophrenia (SCZ) and 780 healthy controls (HCs); the latter groups were recruited by the Italian Network for Research on Psychoses (NIRP) to which our Centre took part. Social cognition was evaluated through The Awareness of Social Inference Test (TASIT). A resampling procedure was employed to balance differences in samples size., Results: All clinical groups (DEL; DEL&#95;SCZ; and SCZ) showed worse performance on TASIT than HCs, except in Sincere scale. No differences between-clinical groups were found, except for Simple Sarcasm, Paradoxical Sarcasm and Enriched Sarcasm scales., Conclusions: SC was impaired in individuals with 22q11.2DS regardless of psychotic symptomatology, similarly to people with SCZ. Therefore, SC deficits may represent potential endophenotypes of SCZ contributing to the vulnerability to psychosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p adj  = 6.73 × 10 -6 ). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n = 618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program.

The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p = .002), verbal IQ was decreased by 8.17 points (p = .0002) and performance IQ was decreased by 4.03 points (p = .028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort., (© 2018 Wiley Periodicals, Inc.)

Introduction: Psychopathological comorbidity in psychiatric patients is a common issue of epidemiological studies. Still, co-diagnoses have been suspected of being an artefact of a defective nosography rather than a realistic representation of multiple disorders co-existing in the same patient. This research aims at studying multiple disorders related to Axis I and Axis II of the DSM-IV in patients suffering from multiple, acute, and recurring psychotic episodes. Further, we aim to explore correlations between multiplicity of disorders and quality of life., Materials and Methods: The experimental sample includes 30 patients having principal diagnoses belonging to the Axis I, regarded as major psychoses, and the control sample includes 39 volunteers, without any present or previous psychotic disorder. As to measuring instruments, two questionnaires have been used: the MOS (Medical Outcomes Study Short Form Health Survey, by Stein et al.) and TALEIA-400A (Test for AxiaL Evaluation and Interview for clinical, personnel, and guidance Applications, by L. Boncori et al.). A multiple analysis of variance has been calculated to verify differences in number of disorders between experimental and control groups, and bivariate correlations to verify negative relationship between co-diagnoses and quality of life., Results: The patients' group showed significantly more disorders than the control group (p = 0.0007); subgroups of patients different in number and quality of co-diagnosis also significantly differed as to overall profile elevation and as to cognitive efficiency; the correlation between co-diagnoses and quality of life is significant and negative (r = -0.62, p < 0.01)., Conclusions: Our data fit to outcomes from other studies showing that comorbidities can be regarded as an index of disorder severity.