Anxiety

Edvard Munch. “Anxiety.” 1894. Oil on Canvas, 94cm x 74cm

It’s been a couple of weeks since my last blog post. I’ve been busily setting up my private practice and have felt as though I’ve been in freefall at times. There is so much to think about, so many things to put into place.

And they teach you none of these in medical school or specialty training. So even the informal chats with other specialists who have set up their own practice is like a foreign language. At least I have a good accountant and a good practice manager to help guide me through this.

But setting up my own business is something I’ve wanted to do since before I even considered a career in medicine. So to me, this is exciting and nerve wracking all at once.

It is with this that I turn my pen towards a topic I’ve wanted to discuss for a while: Anxiety.

What is Anxiety?

Anxiety is more than feeling nervous. There’s a whole constellation of anxiety disorders, ranging from Specific Phobias to Generalised Anxiety Disorder to Panic Disorder. The common thread among all of these disorders is excessive fear and anxiety with associated behavioural disturbances.

Fear and anxiety are often used interchangably, but there is a difference between them. While fear is the emotional response to real or perceived threat, anxiety is the anticipation of future threat. Fear evokes fawn, fight, flight, freeze, or dissociate responses, which each have characteristic symptoms. Anxiety on the other hand involves vigillance and preparation for future danger, or behaviours to avoid confrontation with the anticipated danger.

Anxiety disorders are persistent and out of proportion to the situation. This needs to be placed within developmentally and socioculturally appropriate contexts. And physiological causes also need to be excluded, such as the effects of a substance or other medical pathology.

Anxiety disorders are the most common mental health disorder in Australia, with roughly one in six Australians living with Anxiety in any given year, and females are almost twice as likely to live with Anxiety than males; transgender and gender diverse people have much higher rates of Anxiety than other Australians. Among the Anxiety disorders, Social Anxiety is the most common in Australia.

The Conventional View of Anxiety

Understanding the neuroscience of Anxiety helps to unlock treatement.

The conventional view of Anxiety involves subcortical circuits of the brain. Within this model, a threat stimulates the lateral nucleus of the amygdala, which in turn sends a signal to the central nucleus of the amygdala to induce a physiological response (heart racing, sweating, tremor, dry mouth), which supports defensive behaviours (fight, flight, freeze, dissociate). Meanwhile, the lateral nucleus also sends a signal to the basal nucleus of the amygdala, which in turn triggers the nucleus accumbens to control avoidance behaviours.

Higher brain circuits in the cortex (notably the prefrontal cortex) dampen the effects of these subcortical circuits and are the target of cognitive approaches to psychotherapy. Medication helps to strengthen the control of these higher brain circuits or reduce the intensity of the physiological responses, and so in turn work synergistically with psychotherapy.

I find myself using this model to explain Anxiety disorders in my clinic. But something is missing: conscious experience. Conscious experience is a cortical activity, so the conventional view is of non-conscious fear.

Whilst this brain circuit controls the behavioural and physicological response to a threat, it doesn’t follow that the subjective experience of fear emerges from this brain circuit. After all, subjective experiences of fear and anxiety don’t always correlate with physiological symptoms. Correlation does not prove a cause, but a lack of correlation suggests there is something else going on. There are also a number of neuroscientific papers that highlight how patients with damage to parts of this subcortical fear circuit still have the subjective experience of fear and anxiety.

Moreover, the conventional view describes brain circuits that evolved to protect against predators. There are various other types of fear that involve non-predatory threats, such as deficits in food and fluid.

Returning the Conscious Experience to Neuroscience

Renowned affective neuroscientist Professor Joseph E LeDoux wrote an article a few years ago with Dr Daniel S Pine on this issue. In their heavily cited article, they proposed an alternate approach that places the subjective experience of fear and anxiety in the higher brain.

From: LeDoux JE, Pine DS. Using Neuroscience to Help Understand Fear and Anxiety. American Journal of Psychiatry 2016; 173(11): 1083-93

They separate the behaviour response circuits, such as the traditional view described above, from conscious feeling circuits. On the one hand, this beautifully allows for the experience of fear and anxiety to be shaped by language and culture. On the other hand, it helps to explain why young children have emotional reactions before they are able to name those emotions.

Importantly, this model highlights the limits of what we can learn from the animal studies that provided the evidence for the traditional model. LeDoux and Pine are careful to point out that they “are not necessarily suggesting that animals lack conscious experiences, but rather that it is problematic to draw inferences about conscious experiences, and thus problematic to use words like fear and anxiety, when describing animal behavior and physiology.”

The more recent functional MRI study by Dr Feng Zhou and colleagues supported LeDoux and Pine’s proposal. Their study found that the experience of fear is distributed across multiple brain circuits, both cortical and subcortical. To me, this finding isn’t at all surprising.

Therapeutic Implications

Aside from the need to update my explanations to patients, this new model has enormous implications for therapy.

Importantly, it highlights why pharmacological approaches alone are not sufficient to treat Anxiety. Indeed, animal-models are a fundamental part of pre-clinical drug discovery, and so can only really test the subcortical circuits. However, if the experience of fear and anxiety emerge from cortical circuits, then it is difficult to translate animal behaviours in the lab to the conscious experience of fear and anxiety.

This runs counter to how I have been trained as a clinician. Whilst behavioural change is important, I ultimately want to know how the patient is feeling.

LeDoux and Pine’s model suggests consideration of alternate medications that affect the cortical networks. This may include the off-label use of medication or novel therapeutics tailored to the individual. If the cortical network is where the experience of anxiety and fear resides, then the goal of these alternative medications is to support engagement in psychotherapy.

Conversely, given Anxiety involves multiple brain circuits, both conscious and unconscious, this opens up an enormous world of possibilities in psychotherapy. Cognitive Behaviour Therapy for instance works primarily on cortical networks, but therapy can be derailed by the subcortical networks.

My own clinical experience is that tailoring treatment that works synergistically across multiple domains leads to the best results for patients with Anxiety. This approach is supported by neuroscience.

Now I need to update my approach to explaining fear and anxiety.