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Recent studies highlighted that, starting from ~23 Ma onwards, deformation in Garhwal Himalaya (NW India) localized first in the inner part of the Greater Himalayan Sequence (GHS) along the Badrinath shear zone (BSZ) and subsequently along the Main Central thrust zone (MCTz), made by the upper Vaikrita thrust (VT) and the lower Munsiari 40 39 thrust (MT). Detailed in-situ geochronology by U-Th-Pb on monazite and Ar / Ar on micas demonstrated that these thrust-sense shear zones were active in different times from the older BSZ active at 23-21 Ma, through the VT 20-16 to 9-8 Ma up to the younger MT, active at 5-4 Ma. The consequences are twofold: a) all deformation in the MCTz was not active at the same time but in at different times, as deformation migrated from the upper levels to the lower levels of the GHS in few Myrs. In addition, the static growth of micas after deformation testifies that once deformation migrated to the lower shear zone levels, the levels, the deformation in the upper part ceased; b) the downward sequence of deformation demonstrates that the GHS and Lesser Himalayan Sequence were exhumed by an “in-sequence shearing” deformation resulting in the earlier exhumation of the upper portions of the metamorphic core.

New tectono-metamorphic data along the Alaknanda-Dhauli Ganga valleys in the Garhwal Himalaya (NW India) are presented focusing on sheared rocks of the Main Central Thrust zone (MCTz), one of the first order regional structures in the Himalaya. In regard of large hot orogens (LHOs), the MCTz corresponds to the base of the low-viscosity infrastructure. Our new findings support that the MCTz is a c. 4 km thick mylonitic zone, affecting different lithologies and encompassing a possible (previously defined) protolith boundary. Four selected mylonitic samples, at different structural position along the MCTz, were studied with a multi-disciplinary approach in detail, supporting that an inverted metamorphic field gradient, with temperature (T) and pressure (P) ranging from c. 500 up to c. 700 °C and c. 0.50–0.60 GPa up to >1.0 GPa, was present. This inverted P-T array is also discernable by the distribution of Al-rich minerals (e.g. chloritoid, staurolite, kyanite) in the intercalation of sheared quartzite. In situ U-(Th)-Pb monazite geochronology indicates that the high-T shearing in the upper part of the MCTz mylonites developed from c. 20 Ma on after a stage of prograde metamorphism that lasted until c. 23 Ma. The integration of our data with available structural, metamorphic and geochronological information along the MCTz profile, in the study area, sheds light on the development of the associated inverted metamorphic sequence (IMS). These data carry also empirical finite patterns to be tested against theoretical models investigating the possible roles of viscous heating and “tectonic overpressure” in the development of the IMS in the Himalaya, and possibly in LHOs in general. Both phenomena, if have been active at all, are not obvious in regard of the current state of geothermobarometric methods. On the contrary, a model for the tectonic assembly of the IMS is favored. The anomalous apparent P and T inverted field gradients are interpreted to be the result of the differential and diachronous transport along a shear zone experiencing heterogeneous vertical thinning linked to the non-coaxial flow.

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.

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.

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

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.