It's one of the most common medical conditions on the planet so why are the causes ofanxiety still such a mystery? Scientists are working tounravel them.
Ithappened in a split second, like a bone snapping under pressure.
One minute I was cooking dinner, monitoring babies, bath time, work emails, phone calls, deadlines and life admin. The next, the room was spinning.
I turned, and suddenly the floor began undulating beneath my feet. Negotiating the kitchen was like walking across the Turkey Trot at Coney Island. The walls fell in towards me.
I grabbed the bench to steady myself, but my fingers were tingling and there was a high-pitched ringing in my ears. Yet, I felt like I was trapped inside a glass box: sounds outside were muffled, my vision blurred, my heart racing.
There were no broken bones, but something else cracked that day, something inside my head.
I visited my doctor in a panic but despite the drama of my symptoms, the diagnosis was remarkably straightforward: "What you are describing is commonly felt by people experiencing anxiety," the doc told me gently.
Research suggests more than 25 per cent of us encounter a clinically significant episode of anxiety at some point in life.
For some, it is a fleeting experience like mine and manyanxiety sufferersrespond well to existing treatments including cognitive behaviour therapy or medication. Yet for others, anxiety can be a crippling and chronic disability impacting all areas of life without relief.
The COVID pandemic has supercharged the numbers, with GPs and psychologists reporting a spike in patients seeking help for anxious feelings.
And while researchers emphasise the complexity of the anxiety jigsaw puzzle which can lead to diagnoses including generalised anxiety disorderor obsessive compulsive disorder there are three key areas where cutting edge research is ushering in a new way forward.
No longer is anxiety viewed as arandom condition, as sudden and uncontrollable as the symptoms it can cause.
Instead, genetics, diet and knowledge ofhowtraumatic life events can affect brain structure and development are forging promising new approaches to understanding what causes anxiety, and how to treat it.
Lets break it down.
At the QIMR Berghofer Medical Research Institute in Queensland, PhD candidate Jackson Thorp an expert in psychiatric genetics has spent years hunting for a needle in a haystack.
At the Institute's Translational Neurogenomics Lab, Thorp is using a global database of 400,000 people to identify gene variants more common in anxiety sufferers.
Using statistical analysis software to cross-check the 20,000-25,000 genes in the human genome, Thorps work aims to identify gene changes more common in people with anxiety disorders.
And just last yearThorp and his colleagues hit the jackpot.
"We found 611 genes that were linked to anxiety and many of these are also linked to depression," he says.
"This tells us genetic risk for anxiety does not come from one or two genes but hundreds. Probably even thousands of genes are responsible for increasing the risk of developing anxiety."
Research like this is so new, so pioneering, that a full picture is yet to emerge about which genes are most significant and precisely how they influence anxietys development.
The next step is to understand their role in predisposing someone to anxiety or whether specific genetic mutations could even predict it.
One of the most interesting is a gene known as DRD2, responsible for coding a dopamine receptor in the brain. This neurotransmitter is released when we associate particular activities with pleasure and is related to mental health outcomes.
Yet with Thorps research showing so many genes associated with anxiety, the reality is most of us probably have at least some genetic risk factors.
What makes one person develop an anxiety condition and not another?
"While there is a very large genetic component that does not mean you will definitely develop anxiety, it just means youre more likely to," Thorp explains.
And research reveals exactly how much more likely.
Anxiety disorders are about 30 per cent heritable, Thorp says, noting many people can see anxiety symptoms emerge repeatedly across generations of their own families.
But if genes are behind 30 per cent of our susceptibility to anxiety disorders, what influences the other 70 per cent?
A great many cases of anxiety are triggered by unknown causes, often environmental, Thorp says. "You may have a high genetic risk but if you don't have that environmental trigger then perhaps you wont develop anxiety at all," he says.
The ability for genes to turn themselves on or off in response to environmental triggers is known as epigenetics. It is common across all diseases. A genetic predisposition to diabetes, for example, does not mean you will become ill it increases your risk but how that risk interacts with lifestyle or environment can determine what happens next.
In the case of anxiety, an environmental trigger could be a one-off traumatic experience, sustained disadvantage or common lifestyle stressors.
It could even be living through COVID-19.
A spike in the numbers of people seeking help for anxiety during the pandemic shows in real time the likely role of the environment in triggering genetic susceptibility.
"If we have two people with the same environmental trigger such as the pandemic, why does one develop anxiety but not the other?" asks Thorp. "It's reasonable to ask whether one person has a higher genetic risk."
And it's possible that if it wasnt for COVID-19 that susceptibility may never have been provoked.
The way anxiety changes the structure of the brain and the neurotransmitters it releases consumes Jess Nithianantharajah, a neuroscientist from Melbournes Florey Institute of Neuroscience and Mental Health.
Nithianantharajahs goal is to understand the biological basis of anxiety and "what is really going on in the brain that changes peoples behaviour".
Unlike brain disorders like dementia which are driven by loss of brain capacity, the brain of an anxious person shows "changes in connectivity", Nithianantharajah says. "Certain circuits in the brain become over-connected or under-connected and it's interesting how connectivity changes can lead to impaired behaviours."
In straightforward terms, our human brains are wired to respond to environmental triggers, particularly those that may suggest threat.
When we feel under siege the ancient parts of our brains that developed long before we became the sophisticated humans we are today go into "fight or flight mode".
This process floods our bodies with hormones like adrenaline or cortisol from our endocrine system, as well as neurotransmitters like noradrenaline from the brain, to either fight off the threat or flee from it.
This adaptive reflex has helped humans evolve to identify and respond to danger.
Yet there can be too much of a good thing.
In an anxious brain this response is never properly turned off. Every situation begins to feel like a threat and our bodies react as if they are under fire. Those neural pathways that are meant for emergencies are used repeatedly until they become the go-to response in almost every situation.
Nithianantharajah explains the brains threat "watchman", a tiny nut-shaped structure called the amygdala that sits alongside the hippocampus and encodes danger, becomes hyper-activated.
Neurotransmitters like glutamate that fire up the brain, get out of whack with those like Gammaaminobutyric acid (GABA), designed to calm things down.
The amygdala's crucial connections with the brains pre-frontal cortex which develops until adolescence and acts like the sensible control centre of the brain are broken down, undermining rational thought processes that might tell the amygdala "hey, no worries, you can ease off because this is all good".
"Sometimes it's hard to understand what's the chicken and what's the egg," says Nithianantharajah, adding that within the next few years a toolkit of new treatments may become available to provide more targeted mental health care. "Not everyone who presents with anxiety has the same symptoms and they dont all respond to the same drug," she says.
But what sparks mixed-up connections in the first place?
Sarah Whittle, head of the University of Melbournes Social and Affective NeuroDevelopment Lab, is researching how early life experiences shape brain development and increase the risk of anxiety.
Her fascinating research shows a threatening environment, whether it comes from within the family or from the community, can cause a childs brain to develop faster than normal.
"In essence kids have to grow up quickly to look after themselves," she says. "The circuits in the brain responsible for responding to threat, and regulating emotions, are impacted. Those same circuits are specifically involved in anxiety."
It's suspected that links between the brains ancient "limbic system", including the amygdala, and the controlling prefrontal cortex, are disrupted.
On MRI brain scans Whittle can actually see the impact of this disruption.
Kids that have experienced threat tend to have stronger connectivity between these two brain regions as they develop, she says.
Like so much research into anxiety, the work Whittle does is brand new. Conclusions cannot yet be drawn. The next step is large longitudinal studies in children from diverse backgrounds. One such study involves10,000 US children representing a cross-section of the population.
Researchers will return to these children several times over the next decade, checking their brain structure, function and connectivity and comparing findings with psychological and cognitive development.
"It is crucial when looking at children or adolescents to see how the brain develops over time or we're not getting the whole picture," Whittle says. "Waves of this US study will be coming up over the next five or six years and we'll be able to look in more detail at how trajectories of brain development got off track following exposure to stress and at what age children are most vulnerable."
We have relatively little influence over the way our genes, or the early environments we encounter as children, influence our anxiety risk. But diet is another matter.
Felice Jacka is pioneeringa growing body of research that shows how diet, something over which we all have substantial control, can influence mood.
The link between the gut and the brain is well-known: we have all experienced "butterflies" when we are nervous. Jackas research in "nutritional psychiatry" at Deakin Universitys Mood and Food Centre has made a ground-breaking connection: diet can directly influence mental health.
When Jacka announced the topic would be the focus of her 2010 PhD "many people thought I was quite bananas", she says.
But she persisted. And when her research became the first to demonstrate a correlation between diet quality and the likelihood of having a clinically significant depressive or anxiety disorder Jacka became a sensation. Her work was published on the cover of the prestigious American Journal of Psychiatry and featured in Time magazine.
Further studies continue to strengthen the link, showing those who eat diets high in vegetables and fruits, wholegrains, legumes, nuts and seeds are up to 30 per cent less likely to become depressed.
And Jacka argues that none of this should come as a surprise. The impact of diet is well-established in physical health. Why should mental health be any different?
Yet she is at pains to ensure people do not see their anxiety as a failure of their eating habits: "You did not cause your anxiety," she says.Instead, Jacka wants us to feel empowered: unlike many other risk factors for mental disorders diet is easily manipulated. "Identifying factors we can modify in order to improve mental health outcomes is very, very important," she says.
The scope of Jackas findings are fascinating.
A study of 23,000 Norwegian mothers shows their diet when pregnant is linked to the emotional health of their children, independent of other risk factors.
Another significant association shows diet quality is related to the size of a brain region called the hippocampus, a structure of densely-packed neurons that is unique in its ability to add neural connections throughout life. It is influential in learning and memory as well as mental health.
Jacka saysthe hippocampus can grow or shrink in response to environmental impacts and its size has been linked to anxiety.
"People with mental disorders often have a smaller hippocampus and as they recover the hippocampus grows again," Jacka says. "As people age the hippocampus also tends to get smaller but around 60 per cent of this age-related shrinkage maybe influenced by diet quality."
Jacka conducted a three-month study comparing the impact of diet and social support on moderate-to-severe clinical depression.
"What we saw at the end of that three months was actually quite astounding,"she says. "About a third of (the dietary support cohort) went on to have full clinical remission compared with about 8 per cent in the other condition."
But why does it work?
It is suspected pathways between the gut and brain influence the release of neurotransmitters like serotonin and gamma aminobutyric acid (GABA), two of the bodys most important "feel good" chemicals.
Diet may offer a way to "hack" these chemicals, ensuring our bodies are working optimally, with plenty of happy chemicals available to support and even boost our mood.
In addition, diet influences the function of our immune systems. "And we know that low-grade immune activation, causing inflammation, is an important factor in mental and brain health," Jacka says.
While we wait for the relationship between anxiety, genes, diet and brain structure to deliver new treatments, the ongoing role of psychotherapy in managing symptoms and changing thought patterns to restructure neural pathways cannot be overstated.
Psychologist Peter McEvoy, an anxiety specialist, has devoted many hours of clinical practice to helping people confront and overcome anxiety conditions.
"What causes anxiety is a big question and it's a complex one," says McEvoy, Professor of Psychology at Curtin University, and associate editor of the academic Journal of Anxiety Disorders.
While some individuals may experience anxiety because of "a high genetic load", McEvoy says others are more vulnerable to the "environmental load" including experiences of trauma or pandemic stressors for example.
Notwithstanding these risk factors "we don't really know why one particular individual is going to develop an anxiety disorder and another isn't," he says.
But his years of experience have highlighted one key constant in anxious patients: the need for certainty.
Intolerance of uncertainty, he says, is "ripe for breeding anxiety", noting the "but what if" cycle is a feature of many anxious thoughts. Psychotherapy is excellent at helping patients question these thought cycles.
McEvoy's research into the certainty/uncertainty principle suggests that humans are hard-wired to want to predict the future, a survival instinct that allows us to plan and prevent bad things from happening.
This urge has been quite literally built into the structure of the brain, he says.
Like Nithianantharajah and Whittle, he notes the importance of the pre-frontal cortex in "planning for things and predicting things so we can modify our risk in some way".
Uncertain situations like COVID can set up a battle inside the brain between our innate need to seek certainty, and plan contingencies to keep us safe, while facing a situation that is genuinely uncertain and even out of control.
Some people, McEvoy says, become stuck in a circular pattern of worry, trying to sort out a plan, trying to prevent a bad outcome from a perceived threat, but in reality "if we pursue that goal of achieving certainty, it is likely to lead us down the pathway of excessive worry, and anxiety".
The answer, according to McEvoy, is at once practical and yet, for someone trapped in a cycle of worry, tortuously difficult to achieve: "The goal is to learn to tolerate and accept uncertainty," he says. "To focus more on the here and now and simply ask yourself 'what is controllable today?'.'
How will you know youve reached that place of comfort? For McEvoy the answer is simple: If were still going, then were coping, were resilient. And if were feeling a little exhausted by it then thats ok too.
Words and production: Catherine Taylor
Video:Zalika Rizmal andAndrew McKenzie
Illustrations : Emma Machan
The rest is here:
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