Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study.

PURPOSE: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis. METHODS: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method. RESULTS: Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p < 0.0001) and sarcolemmal sialylation (p = 0.0090) were observed at day 90 compared to baseline. A slower rate of decline was observed for upper extremity strength (p = 0.0139), lower extremity strength (p = 0.0006), and the Adult Myopathy Assessment Tool (p = 0.0453), compared to natural history. Decreased disease progression was estimated at 12 (γ = 0.61 [95% CI: 0.09, 1.27]) and 18 months (γ = 0.55 [95% CI: 0.12, 1.02]) using the GNE-DPM. CONCLUSION: ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients with GNE myopathy.

Adolescents' beliefs about the fairness of exclusion of peers with mental health problems.

Stigma research suggests that exclusion of peers with mental health problems is acceptable, however, no research has explored young people's beliefs about the fairness of exclusion. Group interviews with 148 adolescents explored judgements about the fairness of excluding peers with ADHD or depression from dyads and groups. Young people evaluated exclusion of peers with ADHD or depression from dyads and groups, with the exception of group exclusion of the peer with ADHD, as mostly unfair. Beliefs about the fairness of exclusion were influenced by the attributions that they applied to the target peer's behaviour, social obligations and loyalty within friendships and concerns about the adverse psychological effects of exclusion. Furthermore, their evaluations were influenced by personal beliefs about the social and personal costs of including the target peer. Evaluations of exclusion highlight novel avenues for to develop knowledge on the stigma of mental health problems.

Peer Mental Health Stigmatization Scale: psychometric properties of a questionnaire for children and adolescents.

BACKGROUND: The nature of stigmatizing attitudes towards children and adolescents with mental health problems has received little empirical attention, despite consensus that such attitudes are widespread. As a consequence, much less is known about stigma in childhood and adolescence and methods of stigma measurement are frequently borrowed from the adult literature. For research on this topic to develop, a theoretically based and developmentally appropriate measure is needed. This study aimed to develop a theory-based peer stigma questionnaire suitable for children and adolescents. METHOD: Participants were 562 children and adolescents aged 9-16 years (M = 12.99 years; SD = 1.6 years) in the Republic of Ireland, 316 female, all were White. The Peer Mental Health Stigmatization Scale (PMHSS) contains 24 statements (negative and positive) about peers with mental health problems that are rated on a 5-point scale. Participants also completed the Strengths and Difficulties Questionnaire. Re-test data was collected after 2 weeks from 109 participants. RESULTS: Principal Components Analysis on the negative statements indicate the presence of two components: Stigma Agreement, personal endorsement of stigmatising statements and Stigma Awareness: awareness of prevailing societal stigma towards youth with mental health problems. The positive statements include three components: Intellectual Ability, Recovery and Friendship. CONCLUSIONS: The PMHSS is a psychometrically sound instrument with good retest reliability suitable for use with older children and teenagers. Initial use of the scale suggests that personal endorsement of stigma is lower than perceptions of public stigma.

Explicit and implicit stigma towards peers with mental health problems in childhood and adolescence.

BACKGROUND: Children and adolescents with mental health problems are widely reported to have problems with peer relationships; however, few studies have explored the way in which these children are regarded by their peers. For example, little is known about the nature of peer stigmatisation, and no published research has investigated implicit attitudes thus ensuring that stigma is not well understood. To address this issue, the current study explored patterns of explicit and implicit stigmatisation of peers with depression and attention deficit hyperactivity disorder (ADHD). METHODS: The sample was 385 children (M = 10.21 years) and adolescents (M = 15.36 years). Participants completed a questionnaire assessing explicit stigma towards an age- and gender-matched peer with ADHD or depression and another peer with 'normal issues' who were described in vignettes. They also completed a modified version of the implicit association test (IAT) that explored implicit attitudes towards the target peers. RESULTS: Questionnaire data indicated that the peer with ADHD was perceived more negatively than the peer with depression on all dimensions of stigma, except perceived dangerousness and fear. In contrast, the IAT findings suggest that some participants had more negative views of the peer with depression than the peer with ADHD. Specifically, the findings demonstrate that adolescent males demonstrated significantly stronger negative implicit evaluations of depression compared with younger males and adolescent females. CONCLUSIONS: Children and adolescents demonstrate stigmatising responses to peers with common mental health problems. The nature and extent of these responses depends on the type of problem and the type of measurement used. The findings highlight the importance of using both explicit and implicit measures of stigma.

Psychometric properties of the Peer Mental Health Stigmatization Scale-Revised in adolescents and young adults.

AIM: This study aimed to examine the factorial validity and reliability of the Peer Mental Health Stigmatization Scale (PMHSS) in adolescents and young adults. METHODS: Young people (N = 963) aged 12 to 25 years (M = 16.1, SD = 3.08) were recruited across two studies. Study 1 included adolescents (n = 776) recruited from secondary schools and study 2 included young adults (n = 187) recruited from universities. All participants completed the PMHSS. RESULTS: Exploratory factor analysis resulted in a bi-factorial solution of the PMHSS by retaining 11 items out of the original 16 that loaded on the latent factors of stigma agreement and stigma awareness. Confirmatory factor analysis established the factor structure of the tool in adolescents and young adults. CONCLUSIONS: This shorter version of the PMHSS remains the only validated tool that measures stigma awareness and stigma agreement in youth. We recommend that this version is used in future research.

Retrospective accounts of self-stigma experienced by young people with attention-deficit/hyperactivity disorder (ADHD) or depression.

OBJECTIVE: Little is known about self-stigma experienced by young people with mental health problems, despite the fact that research has demonstrated its existence. In the present study, we sought to investigate the experiences of self-stigma in childhood and adolescence, and particularly the nature of change in self-stigma across this developmental period. Young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) or depression before their 18th birthdays were interviewed about their experiences within their peer groups during childhood and adolescence. METHODS: This qualitative study involved open-ended interviews with 16 young adults aged 18-30 years. Interviews focused on the experience of stigmatization, responses to stigma, and how these changed over time. RESULTS: Three main themes pertaining to self-stigma emerged: (a) being different, (b) peer stigmatization and associated experiences of self-stigma, and (c) selective disclosure and a move toward greater openness. The findings also suggested that the passing of time and changes in young people's social networks and/or degrees of recovery were associated with changes in their experiences of self-stigma. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: During childhood and adolescence, self-stigma is characterized by a sense of being different from peers and negative self-evaluation as a consequence of that difference. However, our findings also demonstrated that some young people were prepared to challenge the stigma they experienced. Further research is needed to understand the factors that contribute to these differing responses and to develop antistigma interventions that facilitate the inclusion of young people with mental health problems in their peer groups.