Search

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.

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.

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.

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.

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

Objective The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

The timing of shearing along the Vaikrita Thrust, the upper structural boundary of the Main Central Thrust Zone in the Garhwal Himalaya, was constrained by combined microstructural, microchemical and geochronological investigations. Three different biotite–muscovite growth and recrystallization episodes were observed: a relict mica-1; mica-2 along the main mylonitic foliation; and mica-3 in coronitic structures around garnet during its breakdown. Electron microprobe analyses of biotite showed chloritization and a bimodal composition of biotite-2 in one sample. Muscovite-2 and muscovite-3 differed in composition from each other. Biotite and muscovite39 Ar–40 Ar age spectra from all samples showed both inter-and intra-sample discrepancies. Biotite step-ages ranged between 8.6 and 16 Ma and muscovite step-ages between 3.6 and 7.8 Ma. These ages cannot be interpreted as ‘cooling ages’ because samples from the same outcrop cooled simultaneously. Instead, the Ar systematics reflect sample-specific recrystallization markers. Intergrown impurities were diagnosed by the Ca/K ratios. The age data of biotite were interpreted as a mixture of true biotite-2 (9.00 ± 0.10 Ma) and two alteration products. The negative Cl/K–age correlation identified a Cl-poor muscovite-2 (>7 Ma) and a Cl-rich, post-deformational, coronitic muscovite-3 grown at ≤5.88 ± 0.03 Ma. The Vaikrita Thrust was active at least from 9 to 6 Ma at c. 600°C; its movement had ended by 6 Ma.

The Himalayan belt has been long studied to deduce large-scale tectonics of shear zones regarding both their kinematics and the age of their timing, especially in the frame of exhumation of the Greater Himalayan Sequence (GHS), the metamorphic core of the orogenic belt. The GHS is delimited at its bottom by an orogenscale shear zone, the Main Central Thrust zone (MCTz), a top-to-the-SW km-thick zone of intensively sheared rocks. As quantitative vorticity analyses in deformed rocks and isotope dating are fundamental in the study of the kinematics of flow and time of activity in shear zones, four samples have been investigated to infer these parameters along the two tectonic boundaries of the MCTz in the Bhagirathi valley: the Munsiari (lower) and the Vaikrita Thrust (upper). To constrain the timing of deformations recorded within the Munsiari and Vaikrita Thrust rocks we undertook 40Ar/39Ar dating. We prepared biotite and muscovite separates with different degrees of purity in order to quantify the bias given by fine-grained impurity phases, which make 100% mica purity unattainable. Combining Argon Differential Release Plots (DRP) with EPMA and Ca-Cl-K signatures of each mica populations we identified the step ages dating deformation. Microstructures of the Munsiari Thrust show the occurrence of a main disjunctive foliation defined by biotite and minor muscovite. 40Ar/39Ar stepheating coupled with correlation diagrams constrains biotite growth on the main foliation at c. 5 Ma. The microstructures of mylonitic micaschists from the Vaikrita Thrust include three different textural generation of micas: a relict foliation, a main mylonitic foliation, and a late generation of static muscovite and chlorite overprinting the relict foliation. 40Ar/39Ar dating constrains muscovite growth on the main foliation around 10 Ma and the growth of large, static muscovite at c. 8 Ma. In the study area, Bhagirathi valley (NW India), our results support an in-sequence shearing from Vaikrita to Munsiari Thrust from c. 10 to c. 5 Ma. Adding information about the kinematic of flow to the age of the bounding shear zones of the GHS is a key purpose for its exhumation models. The use of stable porphyroclasts analysis used for vorticity estimates can suffer from severe limitations, because of the reduction to two dimensions of motion of rigid clasts that is a complex 3D problem. We propose an alternative method to acquire data based on the use of X-ray micro computed tomography that allows to considerably decrease the limitation of the method. We selected the mylonitic orthogneisses from the Munsiari Thrust containing K-feldspar porphyroclasts in order to estimate the kinematic vorticity, which ranges between 0.49 and 0.57. We stress here the importance of a multidisciplinary approach based on detailed meso and microstructural, chemical and geochronological investigations of pervasively sheared rocks from shear zones having multiple generations of fine-grained foliations.

In the Alaknanda-Dhauli Ganga valleys (Garhwal Himalaya, NW India) a nearly complete crustal- structural section of the Himalaya crops out (Jain et al., 2014). In this contribution we present field observations, as well as, microstructural, petrological and geochronological data from the Lesser Himalayan Sequences up to the Tethyan Himalayan Sequence from this area. The pressure-temperature-deformation-time history (i.e. the P-T-d-t path) of selected samples from the Main Central Thrust zone (MCTz) and the up to ductile-sheared portion of the South Tibetan Detachment System (STDS) has been reconstructed with the aid of equilibrium assemblage diagrams, coupled with multiequilibrium and trace-element based thermobarometry after detailed electron microprobe analytical work and microstructural analysis have been performed. U-Th-Pb in situ monazite geochronology from selected samples of key-structural positions (MCTZ up to STDS) allowed us to put an absolute temporal constraint both on the prograde metamorphic history and on the exhumation-related overprint. These data, joined with the geological literature (e.g. Thakur et al., 2015; Hunter et al., 2018), shed light on the tectono-metamorphic evolution of the Himalayan metamorphic core in this portion of the belt. Moreover, these new P-T-d-t paths could be quite well compared with data from other portions of the belt located in Central and Central-Western Nepal (e.g. Iaccarino et al., 2017), since the same approach was followed. Hunter N.J.R., Weinberg R.F., Wilson CJ.L., Luzin W. & Misra S. (2018) - Microscopic anatomy of a “hot-on-cold” shear zone: Insights from quartzites of the Main Central Thrust in the Alaknanda region (Garhwal Himalaya). GSA Bulletin, 130, 1519-1539. Iaccarino S., Montomoli C., Carosi R., Massonne H.-J., Visonà D. (2017) - Geology and tectono-metamorphic evolution of the Himalayan metamorphic core: insights from the Mugu Karnali transect, Western Nepal (Central Himalaya). J. Metam. Geol., 35, 301-325. Jain A.K., Shreshtha M., Seth P., Kanyal L., Carosi R., Montomoli C., Iaccarino S. & Mukherjee P.K. (2014) - The Higher Himalayan Crystallines, Alaknanda – Dhauli Ganga Valleys, Garhwal Himalaya, India. J. Virtual Explorer, 47, Paper 8. Thakur S.S., Patel S.C. & Singh A.K. (2015) - A P-T pseudosection modelling approach to understand metamorphic evolution of the Main Central Thrust Zone in the Alaknanda valley, NW Himalaya. Contrib. Mineral. Petrol., 170, 1-26.

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.

Shear zones play a major role in the tectonic evolution of the orogens and in the exhumation of crystalline rocks. In the Himalaya, two crustal scale shear zones having opposite kinematics bound the Greater Himalayan Sequence (GHS), the metamorphic core of the orogen, along the entire belt: the Main Central Thrust zone (MCTz) and the South Tibetan Detachment System (STDS). The activity time-span of these shear zones has been addressed by many studies, which unsurprisingly give very scattered results, as each study focused on different geological features and followed different mapping, sampling, analytical and interpretive strategies. In the Alaknanda – Dhauli Ganga valleys (Garhwal, NW India) both the STDS and the MCTz crop out in the same transect. The MCTz is a > 1-km thick zone delimited by two distinct thrusts, the Munsiari Thrust at the base and the Vaikrita Thrust, the MCT sensu stricto in the study area, at the top. We selected three representative samples from the Vaikrita Thrust, which crops out in the South of the transect, and three from the the STDS, which crops out in the North of the study area, in order to compare the timing of their activity along the same transect using the same analytical and interpretive approach. Microstructural observations on one garnet-staurolite-bearing quartzite and two garnet-bearing mylonitic micaschists from the Vaikrita Thrust prove the occurrence of three different textural generation of micas: a rare relict foliation, a main mylonitic foliation, and a late generation of static micas forming coronites after garnet breakdown. 40Ar/39Ar step-heating coupled with EMP analyses and with Ca-Cl-K correlation diagrams constrains mica growth on the main foliation around 9 Ma, and coronitic micas at c. 6 Ma (Montemagni et al. 2018b). The STDS deforms the small Malari granite. Deformation microstructures vary according to structural level. In the uppermost sample, a pegmatite intruding the Malari main body, low temperature deformation features are expressed by bulging recrystallization in quartz, bent twins in plagioclase, and kink bands in muscovite. 40Ar/39Ar dating on muscovite give 16.46 ± 0.06 Ma. Structurally below, another pegmatite, intruding the HT-mylonites, was formed during a later, waning deformation stage. Mica shows undulose extinction in quartz and rare kink bands, and yields a younger 40Ar/39Ar age of c. 16.0 Ma. The structurally lowest sillimanite-bearing migmatite shows high temperature deformation microstructures (chessboard extinction and grain boundary migration recrystallization in quartz), followed by static growth of undeformed muscovite, which yields a 40Ar/39Ar age of 14.36 ± 0.06 Ma. This is the minimum age for the cessation of ductile deformation (Montemagni et al. 2018a). Our results demonstrate a diachroneity of STDS and MCT in the Garhwal Himalaya. Any model of exhumation of the GHS should account for this lack of contemporaneity. Montemagni C. et al. (2018a) It. J. Geosci., doi: 10.3301/IJG.2018.07 - Montemagni C. et al. (2018b) Geol. Soc. London Spec. Pub., doi: 10.1144/SP481.3

A peculiar feature of the Himalaya is the occurrence of a system of low-angle normal faults and shear zones, the South Tibetan Detachment System (STDS), at the mountain crests. The STDS was active during synconvergent tectonics. We describe the STDS-related sheared rocks along the Dhauli Ganga valley, in the Garhwal Himalaya (NW India), where the Malari granite, reported as an undeformed igneous body crosscutting the STDS, occurs. A detailed multidisciplinary study, integrating field-based, microstructural, petrographic, and geochronological analyses, was carried out on rocks along this valley. We demonstrate how the noncoaxial ductile portion of the STDS affected the upper part of the Greater Himalaya Sequence migmatite, which experienced peak pressure (P)-temperature (T) conditions of 0.9–1.1 GPa and ≥750°C at ≥24 Ma. This migmatite has been reworked structurally upward leading to the formation of high-T sillimanite-bearing mylonites. Further upward, medium-T shearing deformed the Malari granite and leucogranite dykes, forming medium-T mylonites. Ductile shearing was temporally constrained, based on new in situ monazite datings and previously published Ar-Ar geochronology, between ~20 and 15 Ma. We demonstrate that a preserved ductile to brittle spatial and temporal transition of the STDS deformation exists, with the brittle features overprinting ductile ones. Our data shed new light on the geological evolution of the STDS in the NW Himalaya with implications for the relationship and relative timing of partial melting, granite emplacement, and deformation along low-angle normal faults.

Rationale Variables influencing real-life functioning have repeatedly been modeled in schizophrenia subjects but not systematically investigated in their unaffected first-degree relatives (SRs), in whom milder forms of deficits reported in schizophrenia have been observed, but confounders of clinical cohorts are not in play. Demonstrating that pathways to functional outcome are similar between patients and SRs would validate structural models developed in schizophrenia subjects. The present multicenter study aimed to explore whether variables associated with real-life functioning are similar in schizophrenia patients and their unaffected relatives. Methods The study sample included 921 schizophrenia patients, 379 SRs and 780 healthy controls. Structural Equation Models (SEMs) were used in patients and SRs to test associations of psychopathological dimensions, neurocognition, social cognition, resilience, perceived stigma and functional capacity with real-life functioning domains, impaired in both patients and SRs. Results Interpersonal Relationships and Work Skills were the only functional domains impaired in both patients and SRs. For both domains, functional impairment in patients was found to predict impairment in unaffected relatives, suggesting the involvement of similar illness-related vulnerability factors. In both groups variables significantly associated with Interpersonal Relationships included Social Cognition, Neurocognition, Avolition, Resilience, Disorganization, Perceived Stigma and Gender, and those significantly associated with Work Skills included Social Cognition, Neurocognition and Disorganization. Conclusions Pathways to functional outcome for Interpersonal relationships and Work skills are similar between schizophrenia patients and their unaffected first-degree relatives. These findings validate, in the absence of confounders of clinical cohorts, structural models of determinants of functional outcome in people with schizophrenia.

Deformation and fuid flow in the Munsiari Thrust (NW India): a preliminary fluid inclusion study. A fluid inclusion study was carried out on quartz veins deformed during the activity of the Munsiari Thrust in the Garhwal Himalaya (NW India, Western Himalaya). These veins are hosted in mylonitic phyllites, with a greenschist mineral assemblage made of quartz-white mica-biotite-chlorite-epidote and minor calcite and plagioclase. Within the veins two groups of isolated "early fluid" inclusions and trails of small secondary fluid inclusions have been observed. Two types of inclusions preserved in isolated groups have been petrographycally recognized: (i) a two liquids and a vapor phase (L1+L2+V) that is the most common type and (ii) a less frequent liquid and a vapor phase (L+V). Both types of fluid inclusions were investigated through optical microthermometric experiments. For "early fluid" inclusions, assuming a trapping temperature based on quartz dynamic recrystallization mechanisms and previous P-T estimates, in the range of 500-520°C, a corresponding trapping pressure in the range of c. 0.50-0.53 GPa is estimated. The trapping pressure range evaluated in the present contribution support that these fluid inclusions have been entrapped during the early stages of the activity of the Munsiari Thrust.

none 28 no BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Background The study aimed to assess the construct validity, internal consistency and factor structure of the Specific Levels of Functioning Scale (SLOF), a multidimensional instrument assessing real life functioning. Methods The study was carried out in 895 Italian people with schizophrenia, all living in the community and attending the outpatient units of 26 university psychiatric clinics and/or community mental health departments. The construct validity of the SLOF was analyzed by means of the multitrait–multimethod approach, using the Personal and Social Performance (PSP) Scale as the gold standard. The factor structure of the SLOF was examined using both an exploratory principal component analysis and a confirmatory factor analysis. Results The six factors identified using exploratory principal component analysis explained 57.1% of the item variance. The examination of the multitrait–multimethod matrix revealed that the SLOF factors had high correlations with PSP factors measuring the same constructs and low correlations with PSP factors measuring different constructs. The confirmatory factor analysis (CFA) corroborated the 6-factor structure reported in the original validation study. Loadings were all significant and ranged from a minimum of 0.299 to a maximum of 0.803. The CFA model was adequately powered and had satisfactory goodness of fit indices (comparative fit index = 0.927, Tucker–Lewis index = 0.920 and root mean square error of approximation = 0.047, 95% CI 0.045–0.049). Conclusion The present study confirms, in a large sample of Italian people with schizophrenia living in the community, that the SLOF is a reliable and valid instrument for the assessment of social functioning. It has good construct validity and internal consistency, and a well-defined factor structure.

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 structural analysis of large intracontinental wrench faults is fundamental for deciphering the long-term evolution of continental crust in complex areas in terms of their geodynamic evolution and large-scale crustal block displacements. In this contribution, we demonstrate a pre-Miocene dextral activity of the present-day left-lateral Great Kavir - Doruneh Fault System (GKDFS, Central Iran), one of the major intracontinental active strike-slip faults extending from the Afghan border to the Nain region between Central Iran and the Sanandaj-Sirjan Zone. We document important dextral shearing recorded along a segment of the GKDFS, the Arusan Fault System (AFS), located east of Jandaq, close to the present-day active trace of the GKDFS. The AFS include several ENE-WSW striking strands exposed for a length of more than 50km, which couple pre-Cretaceous ophiolites and metamorphic basement units with the Cretaceous succession of the Khur basin. The fault shows transpressional structures consistent with a dextral shear including thrusts and en échelon folds affecting the Cretaceous carbonate units. Paleostress reconstruction based on mesoscopic fault analysis and related folds geometry allowed to establish vorticity parameters indicating that deformation occurred close to a total simple shear regime with a calculated Wk between 0.9 and 1. The enormous Meso-Cenozoic dextral displacements occurred along the AFS and along the entire GKDFS are attested by the up to several hundreds of kilometers offset of the Paleotethys suture zone, from NE Iran to the western border of Central Iran.

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia.

The Vinschgau Shear Zone (VSZ) is one of the largest and most significant shear zones developed under plastic conditions within the Austroalpine domain, juxtaposing the Ötztal and the Texel units to the Campo, Scharl and Sesvenna units during the building of the Eo-Alpine Orogen. The VSZ dominates the structural setting of a large portion of the central Austroalpine Late Cretaceous thrust stack. In order to fully assess the evolution of the VSZ, a multi-faceted approach based on detailed multiscale structural and petrochronological analyses has been carried out across representative transects of the shear zone in the Vinschgau Valley. The research has been performed with a view to characterizing kinematics, P–T conditions and timing of motion of the VSZ. Our fieldwork-based analyses suggest that the dip angle of mylonitic foliation increases from west to east with an E–W-trending stretching lineation which dips alternatively to the west and to the east, due to later folding related to the Cenozoic crustal shortening. The dominant top-to-W shear sense of the mylonites recognized in the field and confirmed by microstructural analyses led to exhumation of the upper Austroalpine nappes in the hanging wall of the shear zone; the Texel unit with Late Cretaceous eclogites and the Schneeberg and Ötztal units were all affected by Eo-Alpine amphibolite-facies metamorphism. Chemical and microstructural analyses suggest deformation temperatures of ca. 350–400 ∘C during shearing. Timing of deformation along the VSZ has been constrained for the first time through 40Ar/39Ar dating of syn-shearing micas, which reveal a Late Cretaceous age of the VSZ mylonites with ages ranging between 80 and 97 Ma. A systematic younging age of deformation occurs towards the central part of the shear zone in the studied transects. Vorticity analysis shows a clear decrease in the simple shear component correlated to the younging of mica ages towards the core of the shear zone. This evolution is consistent with the growth of a shear zone where shear strain localizes into its central part during deformation. The defined evolution of the VSZ sheds new light on how large-scale thrust-sense shear zones act and how much exhumation they can accommodate in the frame of an evolving orogenic wedge.

Gender differences in clinical and psychosocial aspects of schizophrenia have been widely reported. Findings have not always been consistent, and some of them need further research. In a large sample of community dwelling persons with schizophrenia, we investigated gender differences in clinical, cognitive and functional indices, as well as their changes over a 4-year follow-up and their impact on real-life functioning. Gender differences in personal resources, cognitive and functional indices were explored also in a sample of healthy controls. Men with respect to women had an earlier age of illness onset, a worse premorbid adjustment in the academic domain, more severe avolition, expressive deficit and positive symptoms, lower prevalence of comorbidity for affective disorders, less frequent use of two coping strategies ('religion' and 'use of emotional support') and more frequent positive history of substance and alcohol abuse. In addition, men were more impaired in verbal learning, while women in reasoning/problem solving. Some patterns of gender differences observed in healthy controls were not confirmed in patients. Men's disadvantages in the clinical picture did not translate into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome.

This contribution focuses on geochronological and kinematic data on the Main Central Thrust zone (MCTz) in the Garhwal Himalaya (NW India). A multidisciplinary approach combining detailed 2D and 3D microstructural observations with a new interpretation key of geochronological data on micas is here applied to reconstruct the polyphase evolution of a crustal-scale shear zone. The Ar Differential Release Plot and the use of X-ray micro-Computed Tomography allow to disentangle misleading Ar/Ar spectra of micas from mylonites and to avoid methodological limitation in vorticity estimates, respectively. This new approach allows to unravel the microstructural and petrological complexities linked to the temporal and kinematic evolution of the MCTz. The obtained data indicate a structurally downward shift of deformation, i.e. towards the foreland, across the MCTz, with an increasing pure shear component mirrored to a progressive rejuvenation of the mica age of structures.

Vorticity estimates based on porphyroclasts analysis are limited by the extrapolation to three dimensions of two-dimensional data. We describe a 3D approach based on the use of X-ray micro-computed tomography that better reflects the real 3D geometry of the porphyroclasts population. This new approach for kinematic vorticity analysis in the Munsiari Thrust mylonites, the lower boundary of the Main Central Thrust zone (MCTz) in Indian Himalaya, indicates a large pure shear component during non-coaxial shearing. 40Ar/39Ar ages of micas along the mylonitic foliation of the Munsiari and Vaikrita thrusts (the upper boundary of the MCTz) constrain thrust activity to 5–4 and 8–9 Ma, respectively. Available kinematic vorticity analyses of the Vaikrita mylonites suggest the dominance of a simple shear component. Combining these data, we suggest that the southward and structurally downward shift of deformation along the MCTz was accompanied by a progressive increase in the pure shear component in a general shear flow.

Low-Angle Normal Faults (LANFs) represent in the central Southern Alps area (N Italy) the main structures along which the Variscan basement is in contact with the Upper Carboniferous-Permian volcanic-sedimentary succession. Tourmalinites frequently occur along LANFs, usually replacing former cataclasites. The mineralogy and chemical composition of tourmalinites point to a metasomatic origin. LANFs, together with high-angle faults, controlled the opening of the Permian Orobic Basin and likely acted as a preferred pathway for hydrothermal fluids that triggered the Boron-metasomatism. Along the Aga-Vedello LANF, tourmalinites appear to have formed after the cessation of fault activity, as no brittle post-metasomatism deformation overprint has been observed. These relationships suggest that the circulation of B-rich fluids occurred after the opening of the Orobic Basin that is broadly constrained to the Early Permian. At the same time, ca. 285–270 Ma, a strong magmatic activity affected all the Southern Alps, ranging in composition from mafic to acidic rocks and from intrusions at deep crustal levels to effusive volcanic products. The Early Permian magmatism was likely the source of the late-stage hydrothermal fluids that formed the tourmalinites. The same fluids could also have played a significant role in the formation of the Uranium ore deposit of the Novazza-Vedello mining district, as the ore bodies in the Vedello valley are concentrated along the basement-cover contact.

Constraining the temporal evolution of a shear zone is a key problem in the study of a collisional belt (Challandes et al. 2003) also because shear zones are characterized by intense deformation and are preferential path for fluid circulation leading to mineral reactions, giving rise to difficulties in the interpretation of geochronological data. In the Himalayan belt, the Main Central Thrust zone (MCTz) separates the Greater Himalayan Sequence in the hanging-wall from the Lesser Himalayan Sequence in the footwall. To define the location of the MCTz different criteria have been proposed and its evolution has been investigated related to tectonic models. In the Bhagirathi valley (NW India), the km-wide MCTz is bounded by two narrow thrusts with a top-to-the SW sense of shear: the Munsiari at the bottom and Vaikrita at the top. In order to constrain the timing of deformations recorded within the Munsiari and Vaikrita Thrust rocks we combined microstructural, chemical and 40Ar/39Ar geochronological investigations. Microstructural observations on two mylonitic orthogneisses from the Munsiari Thrust reveal the occurrence of a main disjunctive foliation defined by biotite and rare muscovite. EPMA on biotite reveal that, although similar, biotites from the two samples have different Mg/(Fe+Mg) ratio. The incorporation of Al follows the substitution: Al(tot) <> V IMe2+ + Si4+ + ; incorporation of Ti is accomplished by: Ti4+ + 2O2 <> V IMe2+ + 2OH. 40Ar/39Ar stepheating coupled with Ca-Cl-K correlation diagrams constrains biotite growth on the main foliation at ca. 5 Ma. The microstructures of one mylonitic micaschist from the Vaikrita Thrust include three different textural generation of micas: a well-preserved relict foliation, a main mylonitic foliation, and a late generation of static muscovite together with static chlorite, the latter forming coronites around garnet porphyroclasts. EPMA reveal variable degrees of phengitic substitution IV Al3+ + V IAl3+ <> V IMe2+ + IV Si4+ in muscovites with no differences between the three generations; strongly chloritized biotite is depleted in K. 40Ar/39Ar dating constrains muscovite growth on the main foliation around 8 Ma, similar to age of micas along the main foliation in Dhauliganga valley (Montemagni et al., 2018). For both Munsiari and Vaikrita Thrust we prepared biotite and muscovite separates with different degrees of purity in order to quantify the bias given by fine-grained intergrowths of impurity phases, which make 100% mica purity unattainable. Argon Differential Release Plots (DRP) discriminate the structure collapse of micas sensu stricto from that of impurities. Combining DRP with Ca-Cl-K signatures identifies the step ages reliably dating deformation. Therefore, we emphasize the importance of a multidisciplinary approach based on detailed meso and microstructural, chemical and geochronological investigations in dealing with rocks coming from shear zones and showing the occurrence of multiple generations of fine-grained foliations. In the study area, the Bhagirathi valley (NW Himalaya), our results demonstrate an in-sequence shearing towards the foreland from Vaikrita to Munsiari Thrust from ca. 8 to ca. 5 Ma. Challandes et al. (2003) Chem. Geol., 197, 3-19. Montemagni et al. (2018) Geol. Soc. London Spec. Pub., 481, doi: 10.1144/SP481.3

Importance Enhanced understanding of factors associated with symptomatic and functional recovery is instrumental to designing personalized treatment plans for people with schizophrenia. To date, this is the first study using network analysis to investigate the associations among cognitive, psychopathologic, and psychosocial variables in a large sample of community-dwelling individuals with schizophrenia. Objective To assess the interplay among psychopathologic variables, cognitive dysfunctions, functional capacity, personal resources, perceived stigma, and real-life functioning in individuals with schizophrenia, using a data-driven approach. Design, Setting, and Participants This multicenter, cross-sectional study involved 26 university psychiatric clinics and/or mental health departments. A total of 921 community-dwelling individuals with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic treatment were recruited from those consecutively presenting to the outpatient units of the sites between March 1, 2012, and September 30, 2013. Statistical analysis was conducted between July 1 and September 30, 2017. Main Outcomes and Measures Measures covered psychopathologic variables, neurocognition, social cognition, functional capacity, real-life functioning, resilience, perceived stigma, incentives, and service engagement. Results Of 740 patients (221 women and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core symptoms). The network analysis showed that functional capacity and everyday life skills were the most central and highly interconnected nodes in the network. Psychopathologic variables split in 2 domains, with positive symptoms being one of the most peripheral and least connected nodes. Functional capacity bridged cognition with everyday life skills; the everyday life skills node was connected to disorganization and expressive deficits. Interpersonal relationships and work skills were connected to avolition; the interpersonal relationships node was also linked to social competence, and the work skills node was linked to social incentives and engagement with mental health services. A case-dropping bootstrap procedure showed centrality indices correlations of 0.75 or greater between the original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No difference in the network structure was found between men and women. Conclusions and Relevance The high centrality of functional capacity and everyday life skills in the network suggests that improving the ability to perform tasks relevant to everyday life is critical for any therapeutic intervention in schizophrenia. The pattern of network node connections supports the implementation of personalized interventions.

Objectives: Variants appearing de novo in genes regulating key neurodevelopmental processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may increase the risk for schizophrenia. However, CREs involvement in schizophrenia needs to be explored more deeply. Methods: We investigated de novo copy-number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands by using the Enhancer Chip, a customised array CGH able to investigate the whole genome with a 300-kb resolution, specific disease loci at a ten-fold higher resolution, and which was highly enriched in probes in more than 1,250 enhancer elements selected from Vista Enhancer Browser. Results: In seven patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements. De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain development, while that involving the enhancer element hs1043, also includes ZIC1, which plays a role in neural development and is responsible of behavioural abnormalities in Zic mutant mice. Conclusions: These findings provide further evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia and suggest that CNVs affecting regulatory enhancer elements could contribute to the genetic vulnerability to the disorder.