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Walking too far with arthritis? Here’s how to know when to stop

Walking too far with arthritis? Here’s how to know when to stop

If your knees or hips feel stiff and sore after a long walk, you might wonder whether you're making your osteoarthritis worse. But movement isn’t the enemy—on the contrary, it might be exactly what your joints need. Here's what experts recommend before lacing up your shoes again.

Walking is generally beneficial

Even with osteoarthritis, walking is one of the most joint-friendly forms of exercise—if done mindfully and at your own pace.

The term “wear-and-tear arthritis” is misleading

Osteoarthritis isn’t just about joints being "worn out"—it involves complex changes in cartilage and joint tissue, not simply overuse.

Don’t lose trust in your body

People with osteoarthritis often fear movement, but staying active can prevent stiffness and help maintain joint function.

Start slow and build gradually

If you've been inactive for a while, long walks can be too much. Begin with short walks and slowly increase the distance as strength and balance improve.

Strength training helps

Building muscle around the knees and hips improves stability, reduces pressure on joints, and makes walking less painful.

Physical therapy is a smart first step

A physiotherapist can tailor exercises to your needs, helping you move safely while building up your capacity for longer walks.

Know your pain threshold

Mild pain during or after walking is normal—but it shouldn’t exceed 5 out of 10 on a pain scale, and it should go away by the next day.

Morning soreness is a warning sign

If your joints feel worse the morning after a walk, it’s a sign you may have gone too far. Scale back and find a more comfortable range.

Walk often, not far

Frequent short walks tend to be more effective and manageable than one long, exhausting session.

Your mindset matters

Believing that you can move safely with osteoarthritis can make a real difference. A positive attitude helps reduce pain and encourages consistency.

The deadly and often overlooked risk of birth control

For millions of women, combined hormonal contraceptives are a part of their daily life – providing a convenient and effective option for preventing pregnancy and managing their menstrual cycle.

But new findings are sounding the alarm on a serious, and often overlooked, risk: stroke.

According to recent findings presented at the European Stroke Organisation Conference, combined oral hormonal contraceptives (which contains both oestrogen and progestogen) may significantly increase the chance of women experiencing a cryptogenic stroke. This is a sudden and serious type of stroke that occurs with no obvious cause.

Surprisingly, in younger adults – particularly women – cryptogenic strokes make up approximately 40% of all strokes. This suggests there may be sex-specific factors which contribute to this risk – such as hormonal contraception use. These recently-presented findings lend themselves to this theory.

At this year’s conference, researchers presented findings from the Secreto study. This is an international investigation that has been conducted into the causes of unexplained strokes in young people aged 18 to 49. The study enrolled 608 patients with cryptogenic ischaemic stroke from 13 different European countries.

One of their most striking discoveries was that women who used combined oral contraceptives were three times more likely to experience a cryptogenic stroke compared to non-users. These results stood, even after researchers adjusted for other factors which may have contributed to stroke risk (such as obesity and history of migraines).

It’s well-documented that hormonal contraceptives, which contain both oestrogen and progestin, come with a small, increased risk of experiencing serious health events, including stroke – particularly ischaemic stroke, which occurs when blood flow to part of the brain is blocked.

But a study published earlier this year, which tracked over two million women, found that combined hormonal contraceptives – including the pill, intrauterine devices (IUD), patches and vaginal rings, which all contain both synthetic oestrogen and progestogen – were linked to higher risks of both stroke and heart attack. The vaginal ring increased stroke risk by 2.4 times and 3.8 times for heart attack. The contraceptive patch was found to increase stroke risk by nearly 3.5 times.

Interestingly, they also looked at a progestin-only contraceptive (the IUD) and found there was no increased risk for either heart attacks or strokes.

Both of these recent findings suggest oestrogen may be the main driver of stroke risk. While absolute risk is still low – meaning fewer than 40 in every 100,000 women using a combined hormonal contraceptive will experience a stroke – the population-level impact is significant considering the number of women worldwide who use a combined hormonal contraceptive.

Oestrogen and stroke risk

Combined hormonal contraceptives contain synthetic versions of the sex hormones oestrogen (usually ethinylestradiol) and a progestin (the synthetic version of progestogen).

Natural oestrogen in the body plays a role in promoting blood clotting, which is important for helping wounds heal and preventing excessive bleeding.

But the synthetic oestrogen in contraceptives is more potent and delivered in higher, steady doses. It stimulates the liver to produce extra clotting proteins and reduces natural anticoagulants, tipping the balance toward easier clot formation. This effect, while helpful in stopping bleeding, can raise the risk of abnormal blood clots that can lead to conditions such as stroke. This risk may be even greater for people who smoke, experience migraines or have a genetic tendency to clot.

If a clot forms in an artery that supplies the brain or breaks off and travels through the bloodstream to the brain, this can block blood flow – causing what’s known as an ischaemic stroke. This is the most common type of stroke. Clots can also form in deep veins (such as those in the legs or around your organs).

In addition to clotting, oestrogen may also slightly raise blood pressure and affect how blood vessels behave over time, which can further increase stroke risk.

The effects of oestrogen on clotting may partly explain why the recent conference findings showed a link between combined contraceptive use and cryptogenic stroke risk. Cryptogenic stroke has no obvious cause, but is increasingly being linked to subtle, hidden risk factors – such as hormone-driven clotting.

Understanding risk

These numbers can sound alarming at first, but it’s important to keep them in perspective. The absolute risk – meaning the actual number of people affected – is still low.

For instance, researchers estimate that there may be one additional stroke per year for every 4,700 women using the combined pill.

That sounds rare, and for most users, it is. But when you consider that millions of women use these contraceptives globally, even a small increase in risk can translate into a significant number of strokes at the population level. Which is relative to what is seen with the high number of cryptogenic strokes in young women.

Despite the risks associated with combined hormonal contraceptives, many women continue to use them – either because they aren’t fully informed of the risks or because the alternatives are either less effective, less accessible or come with their own burdens.

Part of the reason this trade-off has become so normalised is the persistent under-funding and under-prioritisation of women’s health research. Historically, medical research has focused disproportionately on men – with women either excluded from studies or treated as an afterthought.

This has led to a limited understanding of how hormonal contraceptives affect female physiology beyond fertility control. As a result, the side-effects remain poorly understood, under-communicated and under-addressed.

Women have a right to make informed decisions about their health and body. This starts with having access to accurate information about the real risks and benefits of every contraceptive option. It means understanding, for example, that while combined hormonal contraceptives do carry a small risk of blood clots and stroke, pregnancy and the weeks following childbirth come with an even higher risk of those same complications. This context is vital for making truly informed choices.

No method of contraception is perfect. But when women are given the full picture, they can choose the method that best suits them.

We also need more research that reflects the diversity and complexity of women’s bodies, not just to improve safety, but to expand options and empower decisions.

Oncologist says men should 'never ignore' six health 'niggles'

An oncologist is urging men not to ignore ‘niggly’ health concerns, as taking action could save their lives. The odd ache and pain isn’t usually something to worry about, but with data showing how often men contact their GP, oncologists are worried life-altering conditions, like cancer, could be getting found too late.

According to a recent ONS Health Insight Survey, just 33.5% of men had attempted to make contact with their GP practice for themselves or someone else in their household in the last 28 days. This is compared to 45.8% of women.

Dr Jiri Kubes, radiation oncologist at the Proton Therapy Center, said: “We know men are less likely to book in to see their GP, and these latest figures show this is a continuing trend."

Dr Kubes has listed six 'niggly' symptoms men should never ignore.

Back pain

Often dismissed as part of getting old, back pain is one of those niggles that can be ignored.

Dr Kubes said: “Back pain is usually musculoskeletal but persistent or deep pain in the lower back or hips requires attention.

“If it’s getting worse or doesn’t improve at home after a few weeks, it’s time to call your GP.”

Persistent fatigue

Another symptom many may link to aging, but feeling constantly fatigued can be linked to many serious illnesses.

“Ongoing fatigue, even after proper rest, could be a subtle sign of many underlying conditions, including cancer, especially if it’s accompanying other symptoms,” Dr Kubes said.

Unintentional weight loss

If you have suddenly started to lose weight and haven’t changed your diet or exercise habits, it’s time to call your GP.

Dr Kubes said: “Sudden weight loss with no obvious reason should always be discussed with your doctor.

“It could be down to a number of different reasons, for example stress, but it could also be linked to serious illnesses such as cancer.”

Lumps and bumps

Any changes to your body that are not normal for you should be discussed with a GP as soon as possible.

Dr Kubes said: “Any unusual swelling, lumps or bumps anywhere on the body should not be ignored.

“There could be a very innocent explanation, or it could be something serious that needs attention.”

Sore throat

It could be just a cold, but if a painful throat is lingering, it could be something else.

“Having a sore throat for longer than three weeks is worthy of a call to your GP,” Dr Kubes said.

“If it’s accompanied by hoarseness or difficulty swallowing then it could be an early sign of throat cancer.”

Urinary changes

Changes to toilet habits can indicate something is wrong.

“Changes in urinary flow - whether it’s a weak stream, difficulty starting, or the sensation of incomplete emptying - are symptoms we routinely investigate for urological cancers,” Dr Kubes said.

I was homeschooled I torment myself with how much I could have achieved

Homeschooling is on the rise in England. The number has risen by more than 10,000 since last year. Parents cite mental health as the main driver. Alex Sergent, 40, was homeschooled as a child and then later as a teen because of his mental health issues. Decades later, he reflects on his experience and the impact it had. (Photo: Supplied)

Homeschooled twice

“Growing up, I was homeschooled twice. The first time, I was just six and I was struggling to read. My mum was massively concerned and she took me out of primary school. She taught me at home for a year. We would visit a reading specialist every week who had a sound-based method for teaching children literacy. I picked it up quickly. It was such a success story that I was even in the local paper. It might have taken me much longer to learn if I had stayed at school. I think it was the right thing to do at the time. Still, I wasn’t taught any maths, which is probably quite bad. I think I only did about an hour a week with the specialist teacher.”

Missing out on something

“I was only six, so I don’t remember much from that time, but I do remember feeling I was missing out on something. I didn’t see many other children in that year. I was the youngest of four siblings and they were much older and in secondary school, so I didn’t socialise much. I just played video games. My mum sent me back to a different school and I was suddenly top of my class. I was great at spelling and I loved learning. Things were going well.”

Dealing with parents separating

“Then when I was about 12, everything started to change. I started a new school and my parents got divorced – we had to leave our childhood home. My older brother left for university. I used to spend a lot of time with him, so it felt like I had lost so much. I struggled with the change. We moved to the middle of nowhere and so I had to cycle five miles every day to get to school. Even though I loved learning, I decided after two weeks at this new school that I wasn’t going to go any more. My mum let me, which she probably shouldn’t have. She was struggling with her own mental health problems and my dad wasn’t in the picture any more. So I just stayed at home. I was given complete autonomy and with that, I just played video games all day. I even went to the cinema three times a week. This went on for two years.”

Dealing with parents separating

School one thing I could rebel against

“In hindsight, this was a way for me to have control over my life – I loved learning, but school was the only thing I could rebel against. For the next two years, I had a visiting teacher, and I went to a unit for homeschooled children in Norwich for a couple of hours every week. They were in high demand and their resources were stretched so I only studied Maths and English. Although I had tasks and homework, it wasn’t a lot of work. For six months, while I waited to be assigned a visiting teacher, I did no work at all. From October 1996 to April 1997, I had no school education. I loved films and I loved computer games – I did that all day, every day for years. At this point, they hadn’t yet introduced fines for children not attending school. Instead, I had a welfare officer and a child psychologist who would visit as well. Between them, they would try and get me to go back to school.”

'What if I had gone to school?'

“After a few years at home, I decided to join Year 10 when I was 15. I had to force myself to go back to school so that I could get my English and Maths GCSEs. I got a C in Maths through sheer resilience, and I got a B in English. I got my A-levels and I went to university to study politics. Still, in my twenties, I beat myself up a lot. What could I have achieved if I had gone to school? I tormented myself with that question.”

Starting a career

“After graduating, I became a journalist for the BBC, I worked for an MP and now I own my own business. I set up my production company and I also have an investing club TinT (Tap into Tech) that supports start-ups that solve the cost of living crisis, provide mental health support and tackle our environmental challenges. But what if I had gone to school? It is such a sliding door moment that I think about it often. What could I have achieved if I hadn’t skipped so much education? I try not to do regret, but I feel it affected me. In my late teens and early twenties, I got to a point where I didn’t know how to socialise. I’m a natural extrovert but I didn’t know how to be around people my age. I believe that was a byproduct of not going to school because I missed out on the social side of growing up. I didn’t get to spend time with friends and mature by speaking to peers. Though I suppose, on the other hand, I didn’t get bullied.”

Forcing myself to socialise

“I did make some friends when I went to sixth form and I am still friends with one now, so I had a glimmer of normality. Looking back, I gained a lot but I lost too. I like that I was independent and I walked my own path. I love my life now and have a good network of friends, but I had to force myself to socialise and to get out there. Homeschooling isn’t bad if a child is being properly monitored. I didn’t have that. I found it tricky to adjust, as a young adult. I think anyone would have.”

What it’s like to teach neurodiverse children

Zain’s jaw is clenched in fury, his cheeks are crimson and eyes wild as – SLAM – he violently upturns his desk, scattering crayons and pencil shavings in its wake.

Zain* is 11, he has autism and ADHD, and he’s angry because his classmates are out playing on the field and his supervised breaktime with his one-to-one member of staff is later.

This is one of Zain’s most aggressive outbursts, but he’s safe, at least. Even if he is calling me a “b---h”.

From my point of view as head teacher, this upturning of tables is preferable to the time Zain ran from class, climbed a tree and remained there all morning. I was terrified he’d fall, or move higher up the trunk if I tried to get him.

He once also hit me in the face when I stupidly bent to talk to him while he was still in “the red zone” (the angriest mood). “Ow!” I yelped, “that hurt.” At work I kept my cool, but I lost it to my husband later.

Being a primary school head teacher in 2025 is not for the faint-hearted.

Since 2015 I’ve run an Ofsted-rated “good” school in one of the Midlands’ leafiest boroughs. It’s always been hugely rewarding and fitted in well with raising my own family, but especially since Covid it’s become utterly relentless. And the dramatic rise in the number of children with neurodiversity is not insignificant.

It’s worse now than it’s ever been

When I began teaching over 30 years ago, there were children who perhaps struggled socially or were extremely boisterous; “sensitive” or “hyperactive” they might have been called. But less than a handful in every class.

Depending on the severity of their needs, there were more options for autistic children to be educated outside of mainstream education, before the drive to be inclusive became the agenda. Now, according to the National Autistic Society Education Report, 70 per cent attend regular schools.

And ADHD (attention deficit hyperactivity disorder) wasn’t recognised by the National Institute for Health and Care Excellence as a condition in children until 2000, but now globally it’s thought that 5 per cent of children live with it.

The landscape has since changed beyond recognition. Roughly a third of children are neurodiverse across most classes in my school; in other parts of the country there’s probably more. That might mean ADHD, ASD (autism spectrum disorder) or the more general label SEMH (for those with social, emotional and mental health needs).

We have pupils with anxiety so severe that they’re pulling out their eyelashes, picking at their skin, banging their heads on the desk or shutting down completely in class. And aside from the worry of what’s going on in children’s heads, all of the above requires communication with home and subsequent meetings with parents about their child’s welfare and how best to support them.

I am not moaning about neurodiverse children being a problem, or at all suggesting they are not welcome in schools. Certainly, every child deserves the best education we can possibly give them, and as a head teacher I’m passionate about helping to make this happen.

What this means is that I’m spending more of my time firefighting crises, dealing with parents and filling in forms rather than actually leading my school.

We are under-resourced, under-funded and overwhelmed. Of course the children must remain the top priority, always, though it’s making my workload a living nightmare.

Fewer staff, yet more children with additional needs

Zain’s outbursts aren’t uncommon. While the table episode was over quickly – once he’d begun sobbing on the floor and saying “sorry Mrs Turner*” – it still requires more follow-up care.

I had a difficult conversation with his father (who I strongly suspect has AuDHD – both ASD and ADHD – and needs of his own, although he lacks the self awareness to recognise it).

Zain’s teaching assistant – who I pray won’t go off sick again – also had to be offered support.

I’m ashamed to say that some days in this job I return home, walk straight to the fridge and pour myself a large white wine before even saying hello to my husband and teenagers.

And Zain is just one of many pupils who has additional needs in my school of 400.

The short answer to why we are struggling is simply that there are fewer staff and yet more children with additional needs.

Ten years ago I had a full team around me: teaching assistants along with a a bigger senior leadership team, staff who weren’t teaching full-time with enough capacity to manage situations before they spiralled.

Frequently, I’m the only one available when it comes to managing very challenging behaviour – such as when an altercation broke out in the playground between two dads (over football, and fists were involved, I kid you not) or when there’s online bullying on the WhatsApp groups (which primary school age children aren’t even allowed to be on).

In any school – even “nice” primaries like mine where children are fed vegetables and encouraged off their screens – pupil confrontation just happens.

The subtle changes to the classroom

There’s no question that the neurodiversity numbers are increasing. Some of it is better awareness and diagnosis, but there is also a real, noticeable shift towards increasing numbers of children who are sensitive to noise, or cannot cope with change.

Children with ADHD or ASD often struggle with things like turn-taking or losing a game. They thrive on structure and so anything from assemblies and plays to end-of-term discos can completely throw them.

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I've lived with ADHD and autism all my life – this is what it's like to have both

On the surface, classrooms look as they always have – art displays on the walls and children sitting at tables. But look closer and you’ll notice the adjustments.

Some children have stretchy resistance bands tied around their chair legs to kick against – a form of sensory regulation. Others sit on wobble cushions or behind cardboard “study wings” to minimise distraction.

Some wear ear defenders, or have “chew toys” around their necks, because it’s better than them gnawing away on their sleeves.

And in every classroom now there are “calm corners”, where children can quietly decompress with fidget toys.

These strategies were unheard of a decade ago in mainstream schools. Yet they’re not gimmicks but genuinely useful tools which help neurodiverse children function within a mainstream classroom.

As I constantly remind my staff: children with ADHD are not naughty, broken, lacking discipline. They’re just finding their way in a world that often doesn’t make sense to them. Our job is to help them make sense of it, feel safe, calm and therefore capable of learning.

Our Senco (special educational needs co-ordinator) is essential in providing support, advice and training. But again, it all comes down to people. And people cost money. We are not miracle workers, we are educators. Exhausted ones who need support.

Teachers are burning out

I’m not a doctor, and I can only speculate on why neuro diversity is rising – but bad diets, food additives and out-of-control screen time certainly can’t help.

Children today struggle to sit through even a panto – let alone concentrate for a 45-minute lesson – because YouTube has trained their brains for fast dopamine hits. Parents are no better – they arrive at pick-up time clutching mobiles to their cheeks.

The mental load on staff is enormous. We aren’t just teachers any more: we’re social workers, mental health first-aiders, speech and language supporters, and behaviour specialists. We are doing it all with fewer resources, less recognition and endless paperwork.

While I’ve been able to manage my own mental health over the years, I fully understand why colleagues are leaving the profession or taking early retirement. I’m lucky to have a supportive husband and the ability to mostly switch off in the lengthy school holidays, while keeping an eye on emails.

Many teachers quit after five to seven years – they’ve burnt out.

With budgets in crisis, the best, most experienced teachers are now too expensive for schools to afford.

At the end of the day, I’m very proud of what my staff and I do to make our school inclusive, and it’s magical when a strapping young adult comes up to me grinning “Miss, do you remember teaching me?” and tells me all about how they’re getting on.

But in all honesty I’m counting down the three years to my retirement now. When I welcome pupils back for the new term this week, at least one thing will put a smile on my face: Zain’s left to go to secondary school.

Psychotherapist reveals key warning sign that your everyday stress is about to tip you over the edge

It's hard not to feel completely overwhelmed by life at times, but a psychotherapist has shared the one of the critical warning signs that you've gone from worrying about things at a normal level to developing full blown anxiety.

Anxiety is a natural reaction to stress and uncertainty, and can be triggered from anything between making presentation at work to proposing to the love of your life.

But while the feeling of 'nerves' usually subside after the completion of the stressful event, sometimes the anxiety lingers, and for some people, it becomes louder and louder until performing basic tasks becomes an exhausting—and sometimes scary—uphill struggle.

Therapist Clare Patterson, who is registered with the British Association for Counselling and Psychotherapy (BACP), describes anxiety as when 'the body’s alarm system [is] stuck in the ‘on’ position—without a clear, present danger.'

But how do you know that your normal worrying levels have got out of control? Ms Patterson shared eight warning signs that you might be heading towards developing a serious mental illness.

Speaking to The Sun, she said one of the biggest red flags is catastrophising, when you focus on what could go wrong, or you're obsessing about future events which are totally out of your control.

'You might be trying to focus at work but your mind is pinging from, "I forgot to book the dentist" to "Do I have cancer?" to "I should drink more water", all in 30 seconds.'

She added: 'You might lie awake at 2am thinking, "What if I lose my job? What if I can't pay the mortgage? What if I end up homeless?", even when nothing has changed at work.

'You may also catastrophise, always assuming the worst-case scenario. For example, your partner doesn't reply to a message for a few hours and your brain jumps to, "They're in a crash" or "They're leaving me".

You may also be in a meeting and notice every change in someone's tone, face or body language, and be convinced it means something bad about you.'

Catastrophising can leave someone feeling permanently overwhelmed, and cause them to withdraw from their loved ones and routines, which are both other symptoms the mental health expert pinpointed.

'For people with an anxiety disorder, the excessive stress hormones can feel overwhelming...It is not "all in their heads". It is a very real, physiological response.

'A low-level fear with no clear object, like waking up with a pit in your stomach for no reason, just a vague feeling something is going to go wrong today, is also common.

'Some people also find their anxiety is internalised and they keep thinking, "What is wrong with me?"

'You might cancel plans because you're feeling overwhelmed, then spend hours criticising yourself for being "flaky" or "too sensitive".'

Warning signs your anxiety is getting out of control

1. Unable to cope with minor worries

2. Catastrophising

3. Indecisiveness

4. Feeling constantly overwhelmed

5. Withdrawal

6. Up and down emotionally

7. Feeling tense

8. Obsessed with perfectionism

Ms Patterson added that feelings of indecisiveness and perfectionism can also be warning signs that your worrying is getting unhealthy.

She said: 'This often leads a person to second guess even small decisions, like what to wear or what to say in a text.

'Anxiety can lead to perfectionism and procrastination, putting off work because it's never quite good enough.'

Other signs manifest physically; tension in the body, and restlessness.

Ms Patterson said that people who lack 'coping mechanisms'— are at risk of their anxiety becoming out of control.

She defines a coping mechanism as steps someone can take to 'feel safe', which might include positive self-talk, seeking out a familiar face at a party or event, or focusing on their breathing.

But people who are very anxious can find themselves falling into a panic attack.

She said: 'The rational part of their brain may be overwhelmed by the anxiety and so they exist in a fight/flight/freeze state where there is a lack of trust in themselves to cope and manage.

'This can trigger even more anxiety, sending them into a spiral, and even lead to physical symptoms including panic attacks, headaches and dizziness.'

It's estimated that 8 million Britons are living with anxiety, and NHS trusts across the UK are struggling to provide suitable support.

In February, after analysing NHS stats, Rethink Mental Illness found that the longest waits for mental health care are over two years (658 days), more than twice as long as the ones for people needing elective physical health treatment (299 days).

The delays in treatment have seen people turning to online therapy providers, mindfulness self-help books, and in the case of Gen Z, crafting.

Findings from The Power of Making report, commissioned by Hobbycraft and in partnership with mental health charity Mind, surveyed nearly 6,000 people nationwide and found that younger people are turning to crochet and pottery kits to try and calm their anxious minds.

New technology reveals how autism disrupts brain cell communication

Autism affects at least 2% of children in the United States – an estimated 1 in 59. This is challenging for both the patients and their parents or caregivers. What’s worse is that today there are no drugs that treat the main symptoms of autism. That is in large part because we still don’t fully understand how autism develops and alters normal brain function. One of the main reasons it is hard to decipher the processes that cause the disease is that it is highly variable. So how do we understand how autism changes the brain?

Using a new technology called single-nucleus RNA sequencing, we analyzed the chemistry inside specific brain cells from both healthy people and those with autism and identified dramatic differences that may cause this disease. These autism-specific differences could provide valuable new targets for drug development.

I am a neuroscientist in the lab of Arnold Kreigstein, a researcher of human brain development at the University of California, San Francisco. Since I was a teenager, I have been fascinated by the human brain and computers and the similarities between the two. The computer works by directing a flow of information through interconnected electronic elements called transistors. Wiring together many of these small elements creates a complex machine capable of functions from processing a credit card payment to autopiloting a rocket ship. Though it is an oversimplification, the human brain is, in many respects, like a computer. It has connected cells called neurons that process and direct information flow –a process called synaptic transmission in which one neuron sends a signal to another.

When I started doing science professionally, I realized that many diseases of the human brain are due to specific types of neurons malfunctioning, just like a transistor on a circuit board can malfunction either because it was not manufactured properly or due to wear and tear.

RNA messages in the cell drive function

Every cell in any living organism is made of the same types of biological molecules. Molecules called proteins create cellular structures, catalyze chemical reactions and perform other functions within the cell.

Two related types of molecules – DNA and RNA – are made of sequences of just four basic elements and used by the cell to store information. DNA is used for hereditary long-term information storage; RNA is a short-lived message that signals how active a gene is and how much of a particular protein the cell needs to make. By counting the number of RNA molecules carrying the same message, researchers can get insights into the processes happening inside the cell.

When it comes to the brain, scientists can measure RNA inside individual cells, identify the type of brain cell and and analyze the processes taking place inside it – for instance, synaptic transmission. By comparing RNA analyses of brain cells from healthy people not diagnosed with any brain disease with those done in patients with autism, researchers like myself can figure out which processes are different and in which cells.

Until recently, however, simultaneously measuring all RNA molecules in a single cell was not possible. Researchers could perform these analyses only from a piece of brain tissue containing millions of different cells. This was complicated further because it was possible to collect these tissue samples only from patients who have already died.

New tech pinpoints neurons affected in autism

However, recent advances in technology allowed our team to measure RNA that is contained within the nucleus of a single brain cell. The nucleus of a cell contains the genome, as well as newly synthesized RNA molecules. This structure remains intact ever after the death of a cell and thus can be isolated from dead (also called postmortem) brain tissue.

By analyzing single cellular nuclei from this postmortem brain of people with and without autism, we profiled the RNA within 100,000 single brain cells of many such individuals.

Comparing RNA in specific types of brain cells between the individuals with and without autism, we found that some specific cell types are more altered than others in the disease.

In particular, we found that certain neurons called upper-layer cortical neurons that exchange information between different regions of the cerebral cortex have an abnormal number of RNA-encoding proteins located at the synapse – the points of contacts between neurons where signals are transmitted from one nerve cell to another. These changes were detected in regions of the cortex vital for higher-order cognitive functions, such as social interactions.

This suggests that synapses in these upper-layer neurons are malfunctioning, leading to changes in brain functions. In our study, we showed that upper-layer neurons had very different quantities of certain RNA compared to the same cells in healthy people. That was especially true in autism patients who suffered from the most severe symptoms, like not being able to speak.

Glial cells are also affected in autism

In addition to neurons that are directly responsible for synaptic communication, we also saw changes in the RNA of other non-neuronal cells – called glia. Glia play important roles in regulating the behavior of neurons, including how they send and receive messages via the synapse. These may also play an important role in causing autism.

So what do these findings mean for future medical treatment of autism?

From these results, I and my colleagues understand that the same parts of the synaptic machinery which are critical for sending signals and transmitting information in the upper-layer neurons might be broken in many people with autism, leading to abnormal brain function.

If we can repair these parts, or fine-tune neuronal function to a near-normal state, it might offer dramatic relief of symptoms for the patients. Studies are underway to deliver drugs and gene therapy to specific cell types in the brain, and many scientists including myself believe such approaches will be indispensable for future treatments of autism.