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Investigations conducted using conventional manometry and, recently, using high-resolution manometry (HRM), allowed us to explore the field of esophageal motility and understand the potential link between motor features and gastroesophageal reflux disease (GERD) pathogenesis. The management of patients with nonachalasic esophageal motor disorders is often challenging, due to the clinical heterogeneous presentation and the multifactorial nature of the mechanisms underlying symptoms.Several studies, carried out using HRM, have better interpreted the esophageal motor function in patients with esophagogastric junction outflow obstruction (EGJOO), distal esophageal spasm (DES), hypertensive esophagus, and hypomotility disorders. Moreover, HRM studies have shown a direct correlation between reduced esophageal motility, disruption of the esophagogastric junction, and gastroesophageal reflux burden.Pathogenesis, clinical presentation, diagnosis, and treatment of nonachalasic esophageal motor disorders still represent a challenging area, requiring future evaluation by multicenter outcome studies carried out in a large cohort of patients and asymptomatic subjects. However, we believe that an accurate clinical, endoscopic, and HRM evaluation is, nowadays, helpful in addressing patients with nonachalasic esophageal motor disorders to optimal treatment options.

Objectives People with schizophrenia (SCZ) present serious and generalised deficits in social cognition (SC), which affect negatively patients' functioning and treatment outcomes. The genetic background of SC has been investigated in disorders other than SCZ providing weak and sparse results. Thus, our aim was to explore possible genetic correlates of SC dysfunctions in SCZ patients with a genome-wide study (GWAS) approach. Methods We performed a GWAS meta-analysis of data coming from two cohorts made of 242 and 160 SCZ patients, respectively. SC was assessed with different tools in order to cover its different domains. Results We found GWAS significant association between the TMEM74 gene and the patients' ability in social inference as assessed by The Awareness of Social Inference Test; this association was confirmed by both SNP-based analysis (lead SNP rs3019332 p-value = 5.24 × 10-9) and gene-based analysis (p-value = 1.09 × 10-7). Moreover, suggestive associations of other genes with different dimensions of SC were also found. Conclusions Our study shows for the first time GWAS significant or suggestive associations of some gene variants with SC domains in people with SCZ. These findings should stimulate further studies to characterise the genetic underpinning of SC dysfunctions in SCZ.

Objective: Earlier evidence suggested that structural–functional covariation in schizophrenia patients (SCZ) is associated with cognition, a predictor of functioning. Moreover, studies suggested that functional brain abnormalities of schizophrenia may be related with structural network features. However, only few studies have investigated the relationship between structural–functional covariation and both diagnosis and functioning in SCZ. We hypothesized that structural–functional covariation networks associated with diagnosis are related to real-world functioning in SCZ. Methods: We performed joint Independent Component Analysis on T1 images and resting-state fMRI-based Degree Centrality (DC) maps from 89 SCZ and 285 controls. Structural-functional covariation networks in which we found a main effect of diagnosis underwent correlation analysis to investigate their relationship with functioning. Covariation networks showing a significant association with both diagnosis and functioning underwent univariate analysis to better characterize group-level differences at the spatial level. Results: A structural–functional covariation network characterized by frontal, temporal, parietal and thalamic structural estimates significantly covaried with temporo-parietal resting-state DC. Compared with controls, SCZ had reduced structural–functional covariation within this network (pFDR = 0.005). The same measure correlated positively with both social and occupational functioning (both pFDR = 0.042). Univariate analyses revealed grey matter deviations in SCZ compared with controls within this structural–functional network in hippocampus, cerebellum, thalamus, orbito-frontal cortex, and insula. No group differences were found in DC. Conclusions: Findings support the existence of a phenotypical association between group-level differences and inter-individual heterogeneity of functional deficits in SCZ. Given that only the joint structural/functional analysis revealed this association, structural–functional covariation may be a potentially relevant schizophrenia phenotype.

Background Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. Aims To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. Methods The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. Results Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p = 0.010), attention (p = 0.011), verbal memory (p = 0.035), and social cognition (p = 0.001) domains, and an overall lower global cognitive composite score (p = 0.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p = 0.004), real-world interpersonal relationships (p p Conclusions These findings strengthen the notion that ASD symptoms may have a relevant impact on different aspects of the disease, crucial to the life of people with schizophrenia. Prominent ASD symptoms may characterize a specific subpopulation of individuals with SSD.

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Type 2 diabetes mellitus (T2DM) is a complex and demanding chronic condition resulting from the body's inability to adequately produce and or effectively utilize insulin. A wide variety of lifestyle factors are of great importance to the development of T2DM, such as sedentary lifestyle, obesity, physical inactivity, smoking and alcohol consumption. An emerging body of literature suggests that stress and traumatic experiences have a role in the aetiology of T2DM.We recruited a sample of 52 patients with a diagnosis of T2DM and a control group of 48 subjects. Using the Traumatic Experience Checklist (TEC), the Childhood Experience of Care and Abuse Questionnaire (CECA-Q), and the Connor-Davidson Resilience Scale (CD-RISC 25), we investigated the presence of history of traumatic experiences and of childhood experience of neglect and abuse.We found that patients with a diagnosis of T2DM have a higher number of traumatic experiences in their personal history, when compared to the control group.Traumatic experiences or sustained stress exposure may contribute to the onset of T2DM. Neuro-inflammatory and psychoanalytic factors will be discussed to explain such association.We conclude that factors that determine high levels of resiliency can have a protective effect against the development of T2DM while stress and the consequent inflammation can contribute to the development of depression and T2DM. These biological features are analyzed in the psychoanalytical context of theories from Freud, Mahler, and Kohut.

Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic medical emergency usually associated with the use of dopamine antagonists, commonly typical antipsychotic drugs. However, it has been observed that it can occur with atypical antipsychotics as well. NMS is characterized by altered consciousness, fever, rigidity, autonomic instability and high creatine phosphokinase (CPK) blood levels. Here, we report a case of a 44-year-old female patient with history of a treatment-resistant bipolar disorder. She was admitted to our psychiatric ward for severe psychomotor agitation and treated with a therapy based on typical and atypical antipsychotics. During the course of the hospitalization she developed NMS. In this case, the diagnosis was delayed due to the slow and insidious symptom presentation, therefore requiring a differential diagnosis. Autoimmune NMDA receptor encephalitis, catatonic syndrome and malignant catatonia have been excluded. The patient met all the DSM-5 criteria for NMS: exposure to dopamine-blocking agent, severe muscle rigidity, fever, diaphoresis, dysphagia, altered level of consciousness, mutism, tremors, tachycardia, high or labile blood pressure, leukocytosis, high creatine phosphokinase. Since robust evidence-based protocols are lacking, here we discuss the relevance of this case in order to highlight the hurdles of a prompt diagnosis, clinical management of associated complications and treatment possibilities for such emergency.

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem., Highlights Better insight seems associated with depressive symptoms in schizophrenia.Network analyses were used to explore this association in a large sample.Insight was associated with self-depreciation, guilt, and suicidal ideation.Although cross-sectional, data suggest causal direction from insight to depression.

BackgroundThe increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative–control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands’ scores.MethodsMultivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands’ MCCB scores predicted REL neurocognitive performance.ResultsSCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning.ConclusionsIn a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

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 dusters. 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 duster showed positive features of recovery, while the third duster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a some-what '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. (C) 2017 Elsevier B.V. All rights reserved.

Aims.In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach.Method.The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded.Results.During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation.Conclusions.The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

Schizophrenia is a debilitating illness, present in approximately 1% of the global population. It is manifested through positive symptoms including delusions, hallucinations, disorganized thoughts and negative symptoms such as avolition, alogia, and apathy. In 2013 the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has been released and some changes were introduced to make diagnosis of schizophrenia more accurate and precise, but researchers are already studying how to improve again the diagnostic criteria of this disorder. To this regard, we hypothesize two types of schizophrenia: poor adherence and good adherence to treatment schizophrenia. Our supposition is based on the evidence of reduced relapses, rehospitalisations, and better long-term course of illness in those patients with schizophrenia who are non-adherent to treatment. Given that adherence to therapy strongly influences patients attitude to medication, quality of life, and subjective well-being, the hypothesis of introducing adherence as a new schizophrenia specifier is compelling.

Objective: Corrected QT (QTc) interval prolongation is often associated with use of first-generation antipsychotics (FGAs). However, other factors require appropriate consideration, including age and gender, the role of other known medications associated with QTc prolongation, and severe comorbid conditions, such as co-occurring alcohol abuse/dependence. We aimed to study potential mediating roles of different, related, candidate variables on QTc. Methods: We capitalized on data from a large (N = 2366), cross-sectional, national survey, the STAR Network QTc study, using a representative sample of people taking FGAs, and recruited from mental health services across Italy. Results: About one-third of the sample was treated with FGAs, and almost one-tenth of the subjects took a different, additional, drug known to cause QTc prolongation. Our findings confirmed that there is an impact from FGAs, age, gender, alcohol misuse, and concurrent risky drugs on QTc. However, comorbid alcohol abuse/dependence and concurrent risky drugs did not mediate the effect of FGAs on QTc. Conclusions: Our findings showed that FGAs, concurrent risky drugs, and alcohol use disorders prolonged QTc. FGAs had a direct effect on QTc, confirming the need for clinicians to monitor a risk that could lead to sudden unexplained death. Copyright © 2016 John Wiley & Sons, Ltd.