Supported employment for people with severe mental illness: a pilot study of an Italian social enterprise with a special ingredient

BACKGROUND: People with mental disorders are far more likely to be unemployed than the general population. Two internationally recognized, evidence-based models of interventions for employment for people with severe mental health problems are Individual Placement Support and the Clubhouse. In Italy, a common model is the 'social enterprise' (SE), which is a programme run by non-profit organisations that help individuals with disabilities to be employed. Despite SEs spread and relevance in Italy, there are no studies about Italian samples. This paper reports on a pilot evaluation of psychosocial and work outcomes of a SE based in Verona, Italy. The study aims to investigate if people with SMI involved in SE job placements may achieve personal recovery and better outcomes over time, and in comparison with a comparable group of users. METHODS: This is a pilot descriptive study with three components. A longitudinal design that comprised a functioning description of 33 SE members with a psychiatric disability in two time-points (when they joined the SE-on average 5 years before the study recruitment, and at the study recruitment-year 2018); and a repeated collection of job details of the 33 members in three time points: 2 years before the recruitment,-year 2016; 1 year before the recruitment - year 2017; and at the recruitment-year 2018. An assessment at the recruitment time-year 2018, of SE users' satisfaction with the job placement, symptoms, functioning, and quality of life (QoL). A cross-sectional study that compared the 33 SE members at the recruitment time-year 2018, with a matched group of people with the following criteria: living in local supported accommodations, being unemployed and not SE members. The two groups were compared on ratings of psychopathology, functioning, and QoL. Descriptive analyses were done. RESULTS: At the recruitment time - year 2018, all SE participants showed a significant better functioning (p < 0.001) than when they joined the SE-when they had been employed for an average of 5 years. In comparison to the matched group, SE members had significantly better functioning (p = 0.001), psychopathology (p = 0.007), and QoL (p = 0.034). According to their SE membership status, participants comprised trainees (21.2%) and employee members (78.8%). Trainees compared to employees had lower autonomies, functioning, QoL and more severe psychopathology. Over the two years prior to study recruitment, trainees showed stable poor autonomies, while employee members showed a variation from average autonomies in the 2 years before the recruitment time - year 2016, to good ones at the recruitment time - year 2018. Over the two years, all SE members set increasing numbers of objectives in all three domains. All SE participants reported high levels of satisfaction with all aspects of the job placement. CONCLUSIONS: SE that provides tailored support to assist people to gain employment skills may be an effective component in helping recovery from SMI

Exploring gender impact on collaborative care planning: insights from a community mental health service study in Italy

INTRODUCTION: Personal recovery is associated with socio-demographic and clinical factors, and gender seems to influence the recovery process. This study aimed to investigate: i) differences in the recovery goals of men and women users of a community mental health service in Italy; ii) any differences by gender in recovery over six months using the Mental Health Recovery Star (MHRS). METHODS: Service users and staff completed the MHRS together at recruitment and six months later to agree the recovery goals they wished to focus on. Socio-demographic and clinical characteristics and ratings of symptoms (BPRS), needs (CAN), functioning (FPS), and functional autonomy (MPR) were collected at recruitment and six months follow-up. Comparisons between men and women were made using t-tests. RESULTS: Ten women and 15 men completed the MHRS with 19 mental health professionals. Other than gender, men and women had similar socio-demographic, and clinical characteristics at recruitment. Women tended to choose recovery goals that focused on relationships whereas men tended to focus on work related goals. At follow-up, both men and women showed improvement in their recovery (MHRS) and women were less likely to focus on relationship related goals, perhaps because some had found romantic partners. There were also gains for both men and women in engagement with work related activities. Ratings of functional autonomy (MPR) improved for both men and women, and men also showed improvement in symptoms (BPRS) and functioning (FPS). CONCLUSIONS: Our findings suggest that collaborative care planning tools such as the MHRS can assist in identifying individualized recovery goals for men and women with severe mental health problems as part of their rehabilitation

Prosody abilities in a large sample of affective and non-affective first episode psychosis patients

Objective: Prosody comprehension deficits have been reported in major psychoses. It is still not clear whether these deficits occur at early psychosis stages. The aims of our study were to investigate a) linguistic and emotional prosody comprehension abilities in First Episode Psychosis (FEP) patients compared to healthy controls (HC); b) performance differences between non-affective (FEP-NA) and affective (FEP-A) patients, and c) association between symptoms severity and prosodic features. Methods: A total of 208 FEP (156 FEP-NA and 52 FEP-A) patients and 77 HC were enrolled and assessed with the Italian version of the “Protocole Montréal d'Evaluation de la Communication” to evaluate linguistic and emotional prosody comprehension. Clinical variables were assessed with a comprehensive set of standardized measures. Results: FEP patients displayed significant linguistic and emotional prosody deficits compared to HC, with FEP-NA showing greater impairment than FEP-A. Also, significant correlations between symptom severity and prosodic features in FEP patients were found. Conclusions: Our results suggest that prosodic impairments occur at the onset of psychosis being more prominent in FEP-NA and in those with severe psychopathology. These findings further support the hypothesis that aprosodia is a core feature of psychosis

Altered syntactic abilities in first episode patients: An inner phenomenon characterizing psychosis

Background: Research has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs). Methods: A multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered. Results: FEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = −3.2, p = 0.007), locative (z = −4.7, p &lt; 0.001), passive-negative (z = −3.2, p = 0.02), and relative (z = −4.6, p &lt; 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = −4.3, p &lt; 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = −9.2, p &lt; 0.001 and FEP-A: z = −4.4, p &lt; 0.001), total (FEP-NA: z = −8.2, p &lt; 0.001 and FEP-A: z = 3.9, p = 0.002), and active-negative (FEP-NA: z = −5.8, p &lt; 0.001 and FEP-A: z = −3.5, p = 0.01) errors compared to HCs. Conclusions: This study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages

Language production impairments in patients with a first episode of psychosis

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations

Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence

In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P &#60; 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage

Identification and Characterization of a Novel Multipotent Sub-Population of Sca-1+ Cardiac Progenitor Cells for Myocardial Regeneration

The cardiac stem/progenitor cells from adult mice were seeded at low density in serum-free medium. The colonies thus obtained were expanded separately and assessed for expression of stem cell antigen-1 (Sca-1). Two colonies each with high Sca-1 (CSH1; 95.9%; CSH2; 90.6%) and low Sca-1 (CSL1; 37.1%; CSL2; 17.4%) expressing cells were selected for further studies. Sca-1⁺ cells (98.4%) isolated using Magnetic Cell Sorting System (MACS) from the hearts were used as a control. Although the selected populations were similar in surface marker expression (low in c-kit, CD45, CD34, CD31 and high in CD29), these cells exhibited diverse differentiation potential. Unlike CSH1, CSH2 expressed Nanog, TERT, Bcrp1, Nestin, Musashi1 and Isl-1, and also showed differentiation into osteogenic, chondrogenic, smooth muscle, endothelial and cardiac lineages. MACS sorted cells exhibited similar tendency albeit with relatively weaker differentiation potential. Transplantation of CSH2 cells into infarcted heart showed attenuated infarction size, significantly preserved left ventricular function and anterior wall thickness, and increased capillary density. We also observed direct differentiation of transplanted cells into endothelium and cardiomyocytes.The cardiac stem/progenitor cells isolated by a combined clonal selection and surface marker approach possessed multiple stem cell features important for cardiac regeneration

AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11

Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway. MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro. In primary human fibroblasts, activated AKT suppresses MRN complex expression to escalate RAS-induced DNA damage and thereby reinforce oncogene-induced senescence. Taken together, our data demonstrate that deregulation of the PI3K-AKT/ mTORC1/ p70S6K pathways, an event frequently observed in cancer, exert profound effects on genome stability via MRE11 with potential implications for tumour initiation and therapy

The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme.

PURPOSE: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. METHODS: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. CONCLUSIONS: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.The EU-GEI Study is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme, and grant 2012/0417-0 from the São Paulo Research Foundatio