Gene Regulatory Network that Shaped the Evolution of Larval Apical Organ in Cnidaria.

Among non-bilaterian animals, a larval apical sensory organ with integrated neurons is only found in cnidarians. Within cnidarians, an apical organ with a ciliary tuft is mainly found in Actiniaria. Whether this apical tuft has evolved independently in Actiniaria or alternatively originated in the common ancestor of Cnidaria and Bilateria and was lost in specific groups is uncertain. To test this hypothesis, we generated transcriptomes of the apical domain during the planula stage of four species representing three key groups of cnidarians: Aurelia aurita (Scyphozoa), Nematostella vectensis (Actiniaria), and Acropora millepora and Acropora tenuis (Scleractinia). We showed that the canonical genes implicated in patterning the apical domain of N. vectensis are largely absent in A. aurita. In contrast, the apical domain of the scleractinian planula shares gene expression pattern with N. vectensis. By comparing the larval single-cell transcriptomes, we revealed the apical organ cell type of Scleractinia and confirmed its homology to Actiniaria. However, Fgfa2, a vital regulator of the regionalization of the N. vectensis apical organ, is absent in the scleractinian genome. Likewise, we found that FoxJ1 and 245 genes associated with cilia are exclusively expressed in the N. vectensis apical domain, which is in line with the presence of ciliary apical tuft in Actiniaria and its absence in Scleractinia and Scyphozoa. Our findings suggest that the common ancestor of cnidarians lacked a ciliary apical tuft, and it could have evolved independently in the Actiniaria.

Molecular and cellular architecture of the larval sensory organ in the cnidarian Nematostella vectensis.

Cnidarians are the only non-bilaterian group to evolve ciliated larvae with an apical sensory organ, which is possibly homologous to the apical organs of bilaterian primary larvae. Here, we generated transcriptomes of the apical tissue in the sea anemone Nematostella vectensis and showed that it has a unique neuronal signature. By integrating previously published larval single-cell data with our apical transcriptomes, we discovered that the apical domain comprises a minimum of six distinct cell types. We show that the apical organ is compartmentalised into apical tuft cells (spot) and larval-specific neurons (ring). Finally, we identify ISX-like (NVE14554), a PRD class homeobox gene specifically expressed in apical tuft cells, as an FGF signalling-dependent transcription factor responsible for the formation of the apical tuft domain via repression of the neural ring fate in apical cells. With this study, we contribute a comparison of the molecular anatomy of apical organs, which must be carried out across phyla to determine whether this crucial larval structure evolved once or multiple times.

Vocational rehabilitation via social firms: a qualitative investigation of the views and experiences of employees with mental health problems, social firm managers and clinicians.

BACKGROUND: Employment within social firms in the UK is under-developed and under-researched, but a potentially beneficial route to vocational rehabilitation for people with mental health problems. This study explores the views and experiences of employees with mental ill-health, managers of social firms and mental health clinicians, in order to understand the potential value of social firms for the vocational rehabilitation, employment and well-being of people with mental health problems. METHODS: Semi-structured interviews were conducted with 23 employees with mental health problems in 11 social firms in England. A focus group and individual interviews were conducted with 12 managers of social firms. Two focus groups were held with 16 mental health clinicians. Data were analysed using thematic analysis. RESULTS: Most employees expressed very positive views about working in a social firm. In responses from both employees and social firm managers, an overarching theme regarding the supportive ethos of social firms encompassed several related features: openness about mental health issues; peer, team and management support; flexibility; and support to progress and develop skills over time. Managers identified benefits of employing people with mental health problems who were sufficiently recovered. Knowledge of social firms within clinician focus groups was very limited, although clinicians thought they could be a welcome additional vocational resource. CONCLUSIONS: High levels of job satisfaction among social firm employees may be explained by the supportive ethos of these working environments. Social firms have potential to be a helpful addition to the range of vocational pathways available for people with mental ill-health. Further mixed methods investigations of experiences and outcomes in order to understand who engages with and benefits from this form of vocational rehabilitation would be valuable in informing decisions about scaling up the model.

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial.

BACKGROUND: Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. METHODS: CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. RESULTS: Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. CONCLUSIONS: Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered.

The clinical profile of employees with mental health problems working in social firms in the UK.

BACKGROUND: UK social firms are under-researched but are a potentially important vocational option for people with mental health problems. AIMS: To describe the clinical profile, satisfaction levels and experiences of social firms employees with mental health problems. METHOD: Clinical, work and service use characteristics were collected from social firms' employees with mental health problems in England and Wales. Workplace experience and satisfaction were explored qualitatively. RESULTS: Predominantly, social firms' employees (N = 80) report that they have a diagnosis of depression (56%) and anxiety (41%). People with schizophrenia (20%) or bipolar disorder (5%) were a minority. Respondents had low symptom and disability levels, high quality of life and job satisfaction and experienced reductions in secondary mental health service use over time. High-workplace satisfaction was related to flexibility, manager and colleague support and workplace accommodations. CONCLUSIONS: The clinical profile, quality of life and job satisfaction level of employees with mental health problems suggest social firms could be a useful addition to UK vocational services for some people. Current employees mainly have common mental disorders, and social firms will need to shift their focus if they are to form a substantial pathway for the vocational recovery of people currently using community mental health teams.

Implementation of an employment intervention in mental health teams: a naturalistic 1-year employment outcome study in people with severe mental illness.

BACKGROUND: In the UK, the severely mentally ill have high rates of unemployment. AIMS: To (1) evaluate implementation of an employment intervention and (2) test the effectiveness of training an existing staff member in providing the employment intervention (Model A) against the provision of a dedicated employment specialist to a team (Model B). METHODS: An employment service was implemented in five mental health teams, with three teams having an existing team member trained and two teams receiving an additional member of staff to carry out the employment intervention. Work outcomes for the two groups were compared at 1 year. RESULTS: Competitive employment was obtained by 17.7% receiving an employment intervention (10.3%, Model A versus 22.8% Model B). Rates of employment or training obtained were 25.6% (10/39) in Model A versus 35.1% (20/57) in Model B, but the difference was not statistically different. Type of employment service model was not significantly associated with working. CONCLUSION: An employment service can be introduced effectively into mental health teams in the UK and positive employment outcomes achieved in a short space of time. Providing an additional resource is more effective compared to asking existing staff to deliver the intervention alongside other roles.

Social Firms as a means of vocational recovery for people with mental illness: a UK survey.

BACKGROUND: Employment is associated with better quality of life and wellbeing in people with mental illness. Unemployment is associated with greater levels of psychological illness and is viewed as a core part of the social exclusion faced by people with mental illness. Social Firms offer paid employment to people with mental illness but are under-investigated in the UK. The aims of this phase of the Social Firms A Route to Recovery (SoFARR) project were to describe the availability and spread of Social Firms across the UK, to outline the range of opportunities Social Firms offer people with severe mental illness and to understand the extent to which they are employed within these firms. METHOD: A UK national survey of Social Firms, other social enterprises and supported businesses was completed to understand the extent to which they provide paid employment for the mentally ill. A study-specific questionnaire was developed. It covered two broad areas asking employers about the nature of the Social Firm itself and about the employees with mental illness working there. RESULTS: We obtained returns from 76 Social Firms and social enterprises / supported businesses employing 692 people with mental illness. Forty per cent of Social Firms were in the south of England, 24% in the North and the Midlands, 18% in Scotland and 18% in Wales. Other social enterprises/supported businesses were similarly distributed. Trading activities were confined mainly to manufacturing, service industry, recycling, horticulture and catering. The number of employees with mental illness working in Social Firms and other social enterprises/supported businesses was small (median of 3 and 6.5 respectively). Over 50% employed people with schizophrenia or bipolar disorder, though the greatest proportion of employees with mental illness had depression or anxiety. Over two thirds of Social Firms liaised with mental health services and over a quarter received funding from the NHS or a mental health charity. Most workers with mental illness in Social Firms had been employed for over 2 years. CONCLUSIONS: Social Firms have significant potential to be a viable addition to Individual Placement and Support (IPS), supporting recovery orientated services for people with the full range of mental disorders. They are currently an underdeveloped sector in the UK.

Cannabis use and mania symptoms: a systematic review and meta-analysis.

BACKGROUND: Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. METHODS: A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. RESULTS: Six articles met inclusion criteria. These sampled 2391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80-4.90) increased risk for the new onset of manic symptoms. LIMITATIONS: We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. CONCLUSIONS: Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.

Predictors of employment in bipolar disorder: a systematic review.

BACKGROUND: Severe work impairment can be present for a considerable proportion of the course of bipolar disorder (BD) and is costly for governments, services and individuals. Understanding predictors of employment in BD is therefore crucial as some may be susceptible to interventions. We conducted a systematic review of prospective studies in order to identify predictors of employment in people with BD. METHODS: We searched Medline, PsychInfo, EMBASE and Web of Science databases, hand searched 3 journals and used predetermined criteria to select papers for full text inclusion. Sixty seven papers were identified. Nine met inclusion criteria, with a total sample of 3184. RESULTS: Studies included in this review identified cognitive deficits (67%, n=4), depression (43%, n=3) and level of education (33%, n=2) as predictors of employment in BD patients. Bipolar depression not only affects whether someone is employed but also time off work. Even sub-syndromal depression appears to damage employment prospects. Verbal memory and executive functioning appear to be predictors of work functioning. LIMITATIONS: Conclusions are based on a relatively small number of studies and are therefore subject to change with the addition of further studies. A formal meta-regression was not possible due to differences between measures of employment and work functioning. CONCLUSIONS: Better assessment and management of depression and cognitive difficulties could improve the occupational functioning of BD patients. There is a need for high quality longitudinal studies specifically designed to investigate predictors of employment in large bipolar disorder samples.

Investigating mental health risk assessment in primary care and the potential role of a structured decision support tool, GRiST.

Aim To explore current risk assessment processes in general practice and Improving Access to Psychological Therapies (IAPT) services, and to consider whether the Galatean Risk and Safety Tool (GRiST) can help support improved patient care.Background Much has been written about risk assessment practice in secondary mental health care, but little is known about how it is undertaken at the beginning of patients' care pathways, within general practice and IAPT services.Methods Interviews with eight general practice and eight IAPT clinicians from two primary care trusts in the West Midlands, UK, and eight service users from the same region. Interviews explored current practice and participants' views and experiences of mental health risk assessment. Two focus groups were also carried out, one with general practice and one with IAPT clinicians, to review interview findings and to elicit views about GRiST from a demonstration of its functionality. Data were analysed using thematic analysis.Findings Variable approaches to mental health risk assessment were observed. Clinicians were anxious that important risk information was being missed, and risk communication was undermined. Patients felt uninvolved in the process, and both clinicians and patients expressed anxiety about risk assessment skills. Clinicians were positive about the potential for GRiST to provide solutions to these problems.Conclusions A more structured and systematic approach to risk assessment in general practice and IAPT services is needed, to ensure important risk information is captured and communicated across the care pathway. GRiST has the functionality to support this aspect of practice.