Posted on May 19, 2021May 23, 2021 Autism

Of mice and men: Mutation linked to autism impairs oxytocin-mediated social behavior

Mutations associated with autism can inhibit the release of the bonding hormone oxytocin and cause abnormal social behavior in mice

Researchers understand the neurobiology of autism and develop effective treatments for it. CREDIT Tokyo University of Science

Autism r is a neurodevelopmental condition involving impaired social abilities, and this makes it a fascinating subject for neuroscientists like Prof. Teiichi Furuichi of the Tokyo University of Science who study the neuroscience of social behavior. Prof. Furuichi and his colleagues have previously worked on developing mouse models of autism to unravel the condition’s neurochemical mechanisms, and in a paper recently published in the prestigious Journal of Neuroscience, they provide evidence that a genetic mutation associated with autism can impair the release of a peptide called oxytocin that plays an important role in regulating social behavior. This finding promises to broaden our understanding of the neurobiology of social behavior.

The gene that Prof. Furuichi’s team chose to study is Caps2, which encodes a protein called Ca²⁺-dependent activator protein for secretion 2 (CAPS2) that regulates the release of brain chemicals (or “neurotransmitters”). Previous studies have shown that CAPS2 deficiencies in mice cause behavioral impairments such as reduced sociality, increased anxiety, and disrupted circadian rhythms. Furthermore, a study of Japanese patients with autism spectrum disorder revealed that some of them had Caps2 mutations that adversely affect the CAPS2 protein’s functions. Prof. Furuichi and his colleagues had previously discovered that the CAPS2 protein is expressed in neurons in the hypothalamus and pituitary gland that release the neuropeptide oxytocin. This information formed the basis of their recent study. As Prof. Furuichi explains, “We hypothesized that CAPS2 deficiencies in mice should alter oxytocin release, which should in turn result in impaired social behavior.”

To test this hypothesis, researchers Shuhei Fujima, Graduate Student at Tokyo University of Science; Yoshitake Sano, Junior Associate Professor at Tokyo University of Science; Yo Shinoda, Associate Professor at Tokyo University of Pharmacy and Life Sciences; Tetsushi Sadakata, Associate Professor in Gunma University; Manabu Abe, Associate Professor at Niigata University; and Kenji Sakimura, a Fellow of Niigata University, among others, led by Prof. Furuichi conducted a series of experiments involving mice that carried genetic alterations that prevented them from expressing the CAPS2 protein. These mice had lower-than-normal oxytocin levels in their blood but higher-than-normal oxytocin levels in the hypothalamus and pituitary gland. The researchers interpreted this finding as evidence that CAPS2 deficiencies impede the normal release of oxytocin from these brain regions into the bloodstream.

Unsurprisingly, the reduced bloodstream levels of oxytocin had clear behavioral effects. When placed inside a rectangular box, the oxytocin neuron-specific CAPS2-deficient mice were unwilling to spend much time in the center of the box, and the researchers interpreted this as evidence of increased anxiety about the risk of a predator attacking them. The CAPS2-deficient mice also exhibited diminished willingness to engage in social interactions when introduced to unfamiliar mice. Interestingly, spraying an oxytocin solution into the noses of the CAPS2-deficient mice acted to restore their willingness to socially interact with unfamiliar mice.

Based on these findings, Prof. Furuichi and his colleagues conclude that the CAPS2 protein plays a critical role in facilitating the release of peripheral oxytocin into the bloodstream. They similarly suggest that CAPS2 is also involved in the release of central oxytocin into the brain regions relating to the control of sociality. Given the key role that oxytocin plays in regulating social behaviors, this could help to explain how mutations in the Caps2 gene could lead to atypical patterns of social behavior in persons with autism spectrum disorder. When asked about the social significance of his team’s work, Prof. Furuichi remarks, “We believe that this research, although basic, is an important achievement that will contribute to the development of tools for the early molecular diagnosis and effective treatment of autism spectrum disorder.”

Given the relatively high prevalence of autism and how extremely disabling severe cases can be, the development of effective treatments would have major benefits for people with autism and the society as a whole.

Posted on May 18, 2021May 23, 2021 Autism

Autistic people across Europe have struggled to access COVID-19 services during pandemic

Likely result: rises in associated deaths, ill health, and poor quality of life, warn authors

Autistic people across Europe have not only struggled to access standard health and care services during the pandemic, but, crucially, also those for COVID-19, finds research published in the online journal BMJ Open.

The likely consequences of this widening of existing health inequalities for this community, will have been to increase associated deaths, ill health, behavioural issues and poor quality of life, warn the authors.

Amid concerns that the pandemic had excluded some vulnerable groups from health and care services, the researchers reviewed the regional and national policies and guidelines of 15 European Union countries on access to COVID-19 treatment for autistic people, published between March and July 2020.

They looked specifically at autistic people’s access to COVID-19 testing; provisions for hospital and intensive care treatment; and changes to standard health and social care services.

They also analysed survey data from Autism-Europe on the lived experiences of 1301 autistic people and caregivers in the included countries: Spain; Italy; Greece; the Netherlands; Switzerland; France; the UK; Germany; Malta; Belgium; Luxembourg; Austria; Ireland; Poland; and Portugal.

The findings showed that autistic people experienced significant barriers when accessing COVID-19 services.

Despite being at heightened risk of serious illness, if infected with coronavirus, because of co-existing health conditions, autistic people weren’t prioritised for COVID-19 testing.

The authors point out that between 5% and 25% of autistic people live in residential care, with up to a further 27% living in supported accommodation, where transmission rates were high in the first wave of the pandemic.

Even in countries where those with underlying conditions and those living in ‘high risk’ settings were prioritised for access to testing, there was no guidance for those living in supported accommodation and the community.

Nor was there any guidance on enhancing the tolerability (and therefore accessibility) of test procedures for autistic people, many of whom have sensory sensitivities around swabbing, for example, and don’t cope well with changes to their routine, such as visiting unfamiliar test sites, note the researchers.

Second, many COVID-19 outpatient and inpatient treatment services were extremely hard to access, largely because of individual differences in communication needs–access to use phone services, for example.

Third, intensive care unit triage protocols in many European countries directly or indirectly excluded autistic people from life-saving treatments.

Many of these protocols require ‘frailty assessments’ which refer to an individual’s dependency on others for assistance with daily care needs and personal care.

While the unsuitability of these assessments for autistic people was recognised in some countries, including in the UK and the Netherlands, measures to prevent the misapplication of frailty and cognitive function assessments haven’t been implemented systematically across European countries, note the researchers.

Finally, abrupt interruptions to standard health and social care with no mitigating measures in place left over 70% of autistic people without everyday support, the survey responses showed.

Around a third of those surveyed said they required daily support (35%; 451) and another third said they required occasional support with routine activities of daily living (33%; 431).

Many services were already stretched before the pandemic, including autism diagnostic services, for which average waiting times can be well over a year, while many community services for autistic people were forced to close, say the authors.

In light of their findings, they make a raft of policy and clinical practice recommendations to reduce health and social care inequalities for autistic people across Europe during public health emergencies.

These “require particularly urgent consideration to enhance the future care of autistic people both during and beyond the pandemic,” they conclude.

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Posted on May 17, 2021May 17, 2021 Pain Management

Managing chronic pain with 10 Minute CBT

This clip contains an excerpt from the DVD “10 Minute CBT in practice: Physical Health and long-term conditions”. In this scenario, a GP demonstrates simple CBT strategies for managing a patient with chronic back pain.