Adapting safety plans for autistic adults with involvement from the autism community

Background: Autistic adults are at greater risk of self-harm and suicide than the general population. One promising intervention in the general population is safety planning. We aimed to seek advice from autistic adults and others in the autism community on how to adapt safety plans for autistic adults. Methods: We conducted focus groups with autistic adults (n = 15), family members (n = 5), and service providers (n = 10), about their views of the Autism Adapted Safety Plan (AASP). We also conducted interviews about the acceptability of the AASP with autistic adults who had developed an AASP (n = 8) and with service providers who had supported them (n = 8). We analyzed the focus group and interview transcripts using thematic analysis. Results: Theme 1 highlights conditions needed to make the process of creating the AASP acceptable for autistic adults. This included creating the AASP with someone they could trust and at the right place and time, when they were not in distress or in crisis. Theme 2 describes how safety planning needed to be a creative, flexible, and iterative process. Autistic adults may need help in expressing their emotions and identifying coping strategies, which can be supported through visual resources and suggestions from the service provider. To ensure that the AASP is accessible in times of crisis, it needs to meet the autistic adults' preferences in terms of formatting and how it is stored (i.e., hard copy or electronic). Conclusions: The AASP is a potentially valuable intervention for autistic adults, provided that the process of creating it is flexible and sensitive to individual needs. Further testing of the AASP to assess its clinical effectiveness in reducing suicidal behavior could provide a life-saving intervention for autistic adults

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis

BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust

Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries

BackgroundThe COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that at its most extreme, this may manifest itself in increased suicide rates.MethodsWe sourced real-time suicide data from around the world via a systematic internet search and recourse to our networks and the published literature. We used interrupted time series analysis to model the trend in monthly suicides prior to COVID-19 in each country/area-within-country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic. Countries/areas-within countries contributed data from at least 1 January 2019 to 31 July 2020 and potentially from as far back as 1 January 2016 until as recently as 31 October 2020. We conducted a primary analysis in which we treated 1 April to 31 July 2020 as the COVID-19 period, and two sensitivity analyses in which we varied its start and end dates (for those countries/areas-within-countries with data beyond July 2020).OutcomesWe sourced data from 21 countries (high income [n=16], upper-middle income [n=5]; whole country [n=10], area(s)-within-the-country [n=11]). In general, there does not appear to have been a significant increase in suicides since the pandemic began in the countries for which we had data. In fact, in a number of countries/areas-within-countries there appears to have been a decrease.InterpretationThis is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. It offers a consistent picture, albeit from high- and upper-middle income countries, of suicide numbers largely remaining unchanged or declining in the early months of the pandemic. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic impacts of the pandemic unfold

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Redesign of a Dioxygenase in Morphine Biosynthesis

Opium poppy (Papaver somniferum) produces medicinally important benzylisoquinoline alkaloids, including the analgesics codeine and morphine, in the morphinan pathway. We aligned three dioxygenases that were recently discovered in P. somniferum and subsequently identified the nonconserved regions. Two of these enzymes, codeine O-demethylase (PsCODM) and thebaine O-demethylase (PsT6ODM), are known to facilitate regioselective O-demethylation in morphinan biosynthesis. We systematically swapped the residues that were nonconserved between the PsCODM and PsT6ODM sequences to generate 16 mutant PsCODM proteins that could be overexpressed in Escherichia coli. While wild-type PsCODM can demethylate both codeine and thebaine, one engineered PsCODM mutant selectively demethylates codeine. Use of this reengineered enzyme in the reconstitution of morphine biosynthesis could selectively disable a redundant pathway branch and therefore impact the yields of the downstream products codeine and morphine in subsequent metabolic engineering efforts.National Science Foundation (U.S.) (Predoctoral Fellowship)John Innes CentreUniversity of East Angli

Advancing our understanding of self-harm, suicidal thoughts and behaviours in autism

No abstract available

More than a Catharanthus plant: A multicellular and pluri-organelle alkaloid-producing factory

International audienc

Developmental Methylome of the Medicinal Plant Catharanthus roseus Unravels the Tissue-Specific Control of the Monoterpene Indole Alkaloid Pathway by DNA Methylation

International audienceCatharanthus roseus produces a wide spectrum of monoterpene indole alkaloids (MIAs). MIA biosynthesis requires a tightly coordinated pathway involving more than 30 enzymatic steps that are spatio-temporally and environmentally regulated so that some MIAs specifically accumulate in restricted plant parts. The first regulatory layer involves a complex network of transcription factors from the basic Helix Loop Helix (bHLH) or AP2 families. In the present manuscript, we investigated whether an additional epigenetic layer could control the organ-, developmental-and environmental-specificity of MIA accumulation. We used Whole-Genome Bisulfite Sequencing (WGBS) together with RNA-seq to identify differentially methylated and expressed genes among nine samples reflecting different plant organs and experimental conditions. Tissue specific gene expression was associated with specific methylation signatures depending on cytosine contexts and gene parts. Some genes encoding key enzymatic steps from the MIA pathway were found to be simultaneously differentially expressed and methylated in agreement with the corresponding MIA accumulation. In addition, we found that transcription factors were strikingly concerned by DNA methylation variations. Altogether, our integrative analysis supports an epigenetic regulation of specialized metabolisms in plants and more likely targeting transcription factors which in turn may control the expression of enzyme-encoding genes

Genome assembly of the medicinal plant Voacanga thouarsii

International audienceAbstract The Apocynaceae tree Voacanga thouarsii, native to southern Africa and Madagascar, produces monoterpene indole alkaloids (MIA), which are specialized metabolites with a wide range of bioactive properties. Voacanga species mainly accumulates tabersonine in seeds making these species valuable medicinal plants currently used for industrial MIA production. Despite their importance, the MIA biosynthesis in Voacanga species remains poorly studied. Here, we report the first genome assembly and annotation of a Voacanga species. The combined assembly of Oxford Nanopore Technologies long-reads and Illumina short-reads resulted in 3,406 scaffolds with a total length of 1,354.26 Mb and an N50 of 3.04 Mb. A total of 33,300 protein coding genes were predicted and functionally annotated. These genes were then used to establish gene families and to investigate gene family expansion and contraction across the phylogenetic tree. A transposable element (TE) analysis showed the highest proportion of TE in V. thouarsii compared to all other MIA-producing plants. In a nutshell, this first reference genome of V. thouarsii will thus contribute to strengthen future comparative and evolutionary studies in MIA-producing plants leading to a better understanding of MIA pathway evolution. This will also allow the potential identification of new MIA biosynthetic genes for metabolic engineering purposes

Adapted Suicide Safety Plans to Address Self-Harm, Suicidal Ideation and Suicide Behaviours in Autistic Adults: Protocol for a Pilot Randomised Controlled Trial

BackgroundSuicide prevention is a national priority for the UK government. Autistic people are at greater risk of experiencing self-harm and suicidal thoughts and behaviours than the general population. Safety plans are widely used in suicide prevention but have not yet been designed with and for autistic people. We developed the first safety plan specifically targeting suicidality in autistic adults: the Autism Adapted Safety Plan (AASP). It consists of a prioritised list of hierarchical steps that can be used prior to or during a crisis to mitigate risk of self-harm and suicidal behaviour. This is a pilot study that aims to assess the feasibility and acceptability of the AASPs and the research processes, including the response rates, potential barriers and reach of AASPs, methods of recruitment, what comprises usual care, and economic evaluation methods/tools.MethodsThis is an external pilot randomised controlled trial of a suicide prevention tool aimed at mitigating the risk of self-harm and suicidal behaviour in autistic adults: AASPs. Participants will be assessed at baseline and followed up 1 month and 6 months later. Assessments include questions about self-harm, suicidality, service use, and their experience of the AASP/taking part in the study. Autistic adults who have a clinical autism diagnosis and self-reported history of self-harm, suicidal thoughts, or suicidal behaviours within the last 6 months will be invited to take part in the study. Informed consent will be obtained. Participants will be recruited via community and third sector services (including community settings, autism charities, and mental health charities). They may also “self-refer” into the study through social media recruitment and word of mouth. Ninety participants will be randomised to either develop an AASP or receive their usual care in a 1:1 ratio.DiscussionThe present study will provide an evaluation of the suitability of the processes that would be undertaken in a larger definitive study, including recruitment, randomisation, methods, questionnaires, outcome measures, treatment, and follow-up assessments.Trial registrationISRCTN70594445, Protocol v4: 8/2/22