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Autistic individuals may be more likely to use recreational drugs to self-medicate their mental health

Thu, 01/07/2021 - 23:30

There is significant debate about substance use of autistic adolescents and adults. Some studies indicate that autistic individuals are less likely to use substances, whereas others suggest that autistic individuals are at greater risk of substance misuse or abuse. The team at the Autism Research Centre in Cambridge used a ‘mixed methods’ design to consider both the frequency of substance use among autistic individuals, as well as their self-reported experiences of substance use.

Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about the frequency of their substance use via an anonymous, online survey; of this group, 919 individuals also gave more in-depth responses about their experiences of substance use.

Autistic adults were less likely than non-autistic peers to use substances. Only 16% of autistic adults, compared to 22% of non-autistic adults, reported drinking on three or more days per week on average. Similarly, only 4% of autistic adults reported binge-drinking compared to 8% of non-autistic adults.

There were also some sex differences in patterns of substance use: autistic males were less likely than non-autistic males to report ever having smoked or used drugs. In contrast, the team did not find differences in the patterns of frequency of smoking or drug use between autistic and non-autistic females.

However, despite lower rates of substance use overall, the qualitative findings of the study provide a much less hopeful picture: autistic adults were nearly nine times more likely than non-autistic peers to report using recreational drugs (such as marijuana, cocaine and amphetamines)  to manage unwanted symptoms, including autism-related symptoms.

Drugs were used to reduce sensory overload, help with mental focus, and provide routine, among other reasons. Several autistic participants also indirectly referenced using substances to mask their autism. Past research has shown that this behavioural management (also known as ‘camouflaging’ or ‘compensating’) has been linked to emotional exhaustion, worse mental health, and even increased risk of suicide among autistic adults.

Autistic adolescents and adults were also over three times more likely than others to report using substances to manage mental health symptoms, including anxiety, depression, and suicidal thoughts. Several participants specifically noted that they used drugs for self-medication. However, this self-medication was not always viewed as negative by participants, and several noted that using recreational drugs allowed them to reduce the doses of prescribed medications for mental health conditions, which was a welcome change due to the sometimes significant side effects from their prescribed medications.

Another area of concern was the strong association between vulnerability and substance use among autistic teenagers and adults. Previous work from the Cambridge team suggests that autistic adults may be much more likely to have adverse life experiences and be at greater risk of suicide than others. The findings of the new study indicate that autistic individuals are over four times more likely to report vulnerability associated with substance use compared to their non-autistic peers, including dependence/addiction, using drugs to deal with past trauma, and substance use associated with suicide.

In addition, the study identified two new areas of vulnerability not been previously reported: being forced, tricked, or accidentally taking drugs; and childhood use of substances (at the age of 12 years or younger).

Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, and the lead researcher of the study, said: “Whether or not the substances currently classed as ‘recreational’ could be used medically remains an open question. It is evident that the current systems of health and social care support are not meeting the needs of many autistic teenagers and adults.

“No one should feel that they need to self-medicate for these issues without guidance from a healthcare professional. Identifying new forms of effective support is urgent considering the complex associations between substance use, mental health, and behaviour management—particularly as camouflaging and compensating behaviours are associated with suicide risk among autistic individuals.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “While some of our results suggest lower likelihood of substance use overall, physicians should not assume that their autistic patients aren’t using drugs. Drug use can be harmful so healthcare providers should aim to establish trusting relationships with autistic and non-autistic patients alike to foster frank and honest conversations about substance use.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “We continue to see new areas in which autistic adults experience vulnerability: mental health, physical health, suicide risk, lifestyle patterns, the criminal justice system, and so on. Substance use is now another area that we need to consider when developing new forms of support for autistic individuals. It is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this mark.”

The research was funded by the Autism Research Trust, Rosetrees Trust, Cambridge and Peterborough NHS Foundation Trust, Corbin Charitable Trust, Medical Research Council, Wellcome and the Innovative Medicines Initiative.

Reference
Weir, E., Allison, C., & Baron-Cohen, S. Understanding the substance use of autistic adolescents and adults: a mixed methods approach. The Lancet Psychiatry (2021).

While autistic individuals are less likely to use substances, those who do so are more likely to self-medicate for their mental health symptoms, according to new research from the University of Cambridge and published today in The Lancet Psychiatry.

Spotlight on neuroscienceNeuroscienceautismdrugsElizabeth WeirSimon Baron-CohenCarrie AllisonAutism Research TrustRosetrees TrustCambridge and Peterborough NHS Foundation TrustCorbin Charitable TrustMedical Research CouncilWellcomeInnovative Medicines InitiativeSchool of Clinical MedicineAutism Research CentreIt is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this markSimon Baron-CohenGRAS GRÜNMan smoking


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Scientists identify 160 new drugs that could be repurposed against COVID-19

Wed, 30/06/2021 - 19:00

In a study published today in Science Advances, a team led by researchers at the University of Cambridge’s Milner Therapeutics Institute and Gurdon Institute used a combination of computational biology and machine learning to create a comprehensive map of proteins that are involved in SARS-CoV-2 infection – from proteins that help the virus break into the host cell to those generated as a consequence of infection. By examining this network using artificial intelligence (AI) approaches, they were able to identify key proteins involved in infection as well as biological pathways that might be targeted by drugs.

To date, the majority of small molecule and antibody approaches for treating COVID-19 are drugs that are either currently the subject of clinical trials or have already been through clinical trials and been approved. Much of the focus has been on several key virus or host targets, or on pathways – such as inflammation – where a drug treatment could be used as an intervention.

The team used computer modelling to carry out a ‘virtual screen’ of almost 2,000 approved drugs and identified 200 approved drugs that could be effective against COVID-19. Forty of these drugs have already entered clinical trials, which the researchers argue supports the approach they have taken.

When the researchers tested a subset of those drugs implicated in viral replication, they found that two in particular – an antimalarial drug and a type of medicine used to treat rheumatoid arthritis – were able to inhibit the virus, providing initial validation of their data-driven approach.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute, who led the study, said: “By looking across the board at the thousands of proteins that play some role in SARS-CoV-2 infection – whether actively or as a consequence of infections – we’ve been able to create a network uncovering the relationship between these proteins.

“We then used the latest machine learning and computer modelling techniques to identify 200 approved drugs that might help us treat COVID-19. Of these, 160 had not been linked to this infection before. This could give us many more weapons in our armoury to fight back against the virus.”

Using artificial neural network analysis, the team classified the drugs depending on the overarching role of their targets in SARS-CoV-2 infection: those that targeted viral replication and those that targeted the immune response. They then took a subset of those involved in viral replication and tested them using cell lines derived from humans and from non-human primates.

Of particular note were two drugs, sulfasalazine (used to treat conditions such as rheumatoid arthritis and Crohn’s disease) and proguanil (and antimalarial drug), which the team showed reduced SARS-CoV-2 viral replication in cells, raising the possibility of their potential use to prevent infection or to treat COVID-19.

Dr Namshik Han, Head of Computational Research and AI at the Milner Therapeutics Institute, added: “Our study has provided us with unexpected information about the mechanisms underlying COVID-19 and has provided us with some promising drugs that might be repurposed for either treating or preventing infection. While we took a data-driven approach – essentially allowing artificially intelligent algorithms to interrogate datasets – we then validated our findings in the laboratory, confirming the power of our approach.

“We hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemics.”

The research was funded by LifeArc, the LOEWE Center DRUID, the Bundesministerium für Bildung und Forschung, the European Union’s Horizon 2020 programme, Wellcome and Cancer Research UK.

Reference
Han, N, Hwang, W, Tzelepis, K, & Schmerer, P, et al. Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies. Sci Adv; 30 June 2021

Cambridge scientists have identified 200 approved drugs predicted to work against COVID-19 – of which only 40 are currently being tested in COVID-19 clinical trials.

COVID-19Coronavirusdrug discoveryArtificial intelligencespotlight on future therapeuticsFuture therapeuticsTony KouzaridesNamshik HanLifeArcLOEWE Center DRUIDBundesministerium für Bildung und ForschungEuropean Union Horizon 2020WellcomeCancer Research UK (CRUK)School of Clinical MedicineMilner Therapeutics InstituteWellcome Trust-CRUK Gurdon InstituteWe hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemicsNamshik HangeraltGraphical representation of COVID-19 and networks


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Upgrading PPE for staff working on COVID-19 wards cut hospital-acquired infections dramatically

Tue, 29/06/2021 - 08:20

The findings are reported by a team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust. The research has not yet been peer-reviewed, but is being released early because of the urgent need to share information relating to the pandemic.

Until recently, advice from Public Health England recommended that healthcare workers caring for patients with COVID-19 should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment; if aerosol-generating procedures were being carried out (for example inserting a breathing tube into the patient’s windpipe), then the guidance recommended the use of an FFP3 respirator. PHE has recently updated its guidance to oblige NHS organisations to assess the risk that COVID-19 poses to staff and provide FFP3 respirators where appropriate.

Since the start of the pandemic, CUH has been screening its healthcare workers regularly for SARS-CoV-2, even where they show no symptoms. They found that healthcare workers caring for patients with COVID-19 were at a greater risk of infection than staff on non-COVID-19 wards, even when using the recommended respiratory protective equipment. As a result, its infection control committee implemented a change in respiratory protective equipment for staff on COVID-19 wards, from FRSMs to FFP3 respirators.

Prior to the change in respiratory protective equipment, cases were higher on COVID-19 wards compared with non-COVID-19 wards in seven out of the eight weeks analysed by the team. Following the change in protective equipment, the incidence of infection on the two types of ward was similar.

The results suggest that almost all cases among healthcare workers on non-COVID-19 wards were caused by community-acquired infection, whereas cases among healthcare workers on COVID-19 wards were caused by both community-acquired infection and direct, ward-based infection from patients with COVID-19 – but that these direct infections were effectively mitigated by the use of FFP3 respirators.

To calculate the risk of infection for healthcare workers working on COVID-19 and non-COVID-19 wards, the researchers developed a simple mathematical model.

Dr Mark Ferris from the University of Cambridge’s Occupational Health Service, one of the study’s authors, said: “Healthcare workers – particularly those working on COVID-19 wards – are much more likely to be exposed to coronavirus, so it’s important we understand the best ways of keeping them safe.

“Based on data collected during the second wave of the SARS-CoV-2 pandemic in the UK, we developed a mathematical model to look at the risks faced by those staff dealing with COVID-19 patients on a day to day basis. This showed us the huge effect that using better PPE could have in reducing the risk to healthcare workers.”

According to their model, the risk of direct infection from working on a non-COVID-19 ward was low throughout the study period, and consistently lower than the risk of community-based exposure.

By contrast, the risk of direct infection from working on a COVID-19 ward before the change in respiratory protective equipment was considerably higher than the risk of community-based exposure: staff on COVID-19 wards were at 47 times greater risk of acquiring infection while on the ward than staff working on a non-COVID-19 ward.

Crucially, however, the model showed that the introduction of FFP3 respirators provided up to 100% protection against direct, ward-based COVID-19 infection.

Dr Chris Illingworth from the MRC Biostatistics Unit at the University of Cambridge, said: “Before the face masks were upgraded, the majority of infections among healthcare workers on the COVID-19 wards were likely due to direct exposure to patients with COVID-19.

“Once FFP3 respirators were introduced, the number of cases attributed to exposure on COVID-19 wards dropped dramatically – in fact, our model suggests that FFP3 respirators may have cut ward-based infection to zero.”

Dr Nicholas Matheson from the Department of Medicine at the University of Cambridge, said: “Although more research will be needed to confirm our findings, we recommend that, in accordance with the precautionary principle, guidelines for respiratory protective equipment are further revised until more definitive information is available.”

Dr Michael Weekes from the Department of Medicine at the University of Cambridge, added: “Our data suggest there’s an urgent need to look at the PPE offered to healthcare workers on the frontline. Upgrading the equipment so that FFP3 masks are offered to all healthcare workers caring for patients with COVID-19 could reduce the number of infections, keep more hospital staff safe and remove some of the burden on already stretched healthcare services caused by absence of key staff due to illness. Vaccination is clearly also an absolute priority for anyone who hasn’t yet taken up their offer.”

The research was funded by Wellcome, the Addenbrooke’s Charitable Trust, UK Research and Innovations, and the NIHR Cambridge Biomedical Research Centre.

Reference
Ferris, M, Ferris, R et al. FFP3 respirators protect healthcare workers against infection with SARS-CoV-2. DOI: 10.22541/au.162454911.17263721/v1

When Addenbrooke’s Hospital in Cambridge upgraded its face masks for staff working on COVID-19 wards to filtering face piece 3 (FFP3) respirators, it saw a dramatic fall – up to 100% – in hospital-acquired SARS-CoV-2 infections among these staff.

COVID-19CoronavirushealthcareNational Health Service (NHS)Mark FerrisMichael WeekesNicholas MathesonWellcomeNational Institute for Health Research (NIHR)UK Research and Innovation (UKRI)Addenbrooke’s Charitable TrustSchool of Clinical MedicineDepartment of MedicineMedical Research Council (MRC) Biostatistics UnitAddenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustHealthcare workers – particularly those working on COVID-19 wards – are much more likely to be exposed to coronavirus, so it’s important we understand the best ways of keeping them safeMark FerrisCambridge University Hospitals NHS Foundation TrustHealthcare worker wearing FFP3 mask


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Key mutations in Alpha variant enable SARS-CoV-2 to overcome evolutionary weak points

Tue, 29/06/2021 - 08:00

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation - the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Now, in research published in the journal Cell Reports, researchers show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

The research was led by scientists at the University of Cambridge, MRC-University of Glasgow Centre for Virus Research, The Pirbright Institute, MRC Laboratory of Molecular Biology, and Vir Biotechnology.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, the study’s senior author, said: “Although we first saw this mutation in an immunocompromised patient and then in the Kent – now ‘Alpha’ – variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently.”

Working under secure conditions, Professor Gupta and colleagues used a harmless form of the virus that displays SARS-CoV-2 spike proteins with the H69/V70 deletion to understand how the spike protein interacts with host cells and what makes this mutation so important.

When they tested this virus against blood sera taken from fifteen individuals who had recovered from infection, they found that the deletion did not allow the virus to ‘escape’ neutralising antibodies made after being vaccinated or after previous infection. Instead, the team found that the deletion makes the virus twice as infective – that is, at breaking into the host’s cells – as a virus that dominated global infections during the latter half of 2020. This was because virus particles carrying the deletion had a greater number of mature spike proteins on their surface. This allows the virus to then replicate efficiently even when it has other mutations that might otherwise hinder the virus. 

“When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate,” said Professor Gupta.

“What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response. In other words, the deletion allowed these variants to have their cake and eat it – they were both better at escaping immunity and more infectious.”

Dr Dalan Bailey from The Pirbright Institute, who co-led the research, added: “In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread.”

Bo Meng from the Department of Medicine at the University of Cambridge, first author on the paper, said: “Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on.”

The research was supported by Wellcome, the Medical Research Council, the Bill & Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Reference
Meng, B, Kemp, SA, Papa, G, Datir R, Ferreira, IATM et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role 1 in the variant of concern lineage B.1.1.7. Cell Reports; 8 June 2021; DOI: 10.1016/j.celrep.2021.109292 

One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

COVID-19CoronavirusInfectious diseasesRavindra GuptaBo MengWellcomeMedical Research CouncilBill and Melinda Gates FoundationNational Institute for Health Research (NIHR)School of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Department of MedicineCambridge Fights COVIDNIHR Cambridge Biomedical Research CentreCambridge Infectious DiseasesUnderstanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early onBo MengKevin GrieveMan walking past Stay Alert/Save Lives artwork


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