Interview with Merel Kindt, professor of Experimental Clinical Psychology

Merel Kindt

Photo: Jeroen Oerlemans

 

It usually comes on with a feeling of nervous tension. One moment everything seems on an even keel when suddenly, out of nowhere, a stream of dark and menacing thoughts start flooding your mind. Soon the terror stoked by these thoughts – fear, dejection, a nagging sense of worthlessness – spreads throughout your body and takes hold of it with an iron grip. Your breathing becomes erratic, your vision blurred and it feels like your pounding heart is about to break free from the rib cage than imprisons it. Whereas the world seemed to make perfect sense to you mere seconds ago, it has now morphed into a black hole that is slowly, but surely, devouring you.

Anxiety and panic disorders have a far-reaching impact on the quality of life of millions of people around the world. To the uninitiated, the physical and mental anguish experienced by those suffering from these disorders can be difficult to understand, let alone grasp. For sufferers, however, anxiety disorders have a very real and very profound influence on the way they live and on their dealings with the world around them. No wonder then that a multitude of treatment options exist for such disorders, with Cognitive Behavioural Therapy (CBT) probably being one of the most well known. While many of these therapies have a positive effect, they also have certain drawbacks: they’re time consuming, invasive and in the long-run are often followed by a relapse.

But what if a quicker, more lasting form of treatment was possible?

For several years now Merel Kindt, professor of Experimental Clinical Psychology at the University of Amsterdam, has been conducting research into a new form of therapy that promises to be a game-changer in the treatment of anxiety disorders. The treatment, which combines so-called memory reconsolidation with the use of propranolol, a beta-blocker, has already shown encouraging results during trials and plans are now being made for a larger roll out. ‘An exciting prospect’, says Kindt, whose research forms part of the UvA’s Brain and Cognition research priority area.

What is the exact background to your research?

A perennial question within the field of behavioural neuroscience is can emotional memory change? Although several effective therapies for emotional disorders exist, in many instances such therapies are unsuccessful in the long run with the anxieties eventually resurfacing. An explanation for this recurrence can be found in animal and human research on fear conditioning, whereby an associative fear memory is created by using, for example, pictures in conjunction with administered pain signals, resulting in a learned fear response. The knowledge of this process is also used as a basis to unlearn the fear response. Known as extinction learning, the created fear response is treated by using the same pictures but then without the accompanying pain signal. With time, one slowly sees the fear response diminishing until it eventually disappears. However, when one waits a couple of days or the change the context or environment, one starts to see the fear steadily returning, both in humans and animals.

What we now know from the field of neuroscience is that during the reversal process a new memory trace is formed alongside the original fear memory, which remains intact and is not erased, and these two end up competing with each other. As long as the new memory remains powerful and dominant, the fear is kept at bay. But sometimes the fear memory returns and becomes powerful again. It was this process which made me curious as to whether there was a way to diminish or totally erase the fear memory.

How did your research on the use of propranolol come about?

After obtaining my PhD I went ahead and did a clinical training. Throughout this period, I kept having the same nagging questions: what exactly are we doing? Why do therapies sometimes work and sometimes fail? What exactly are the underlying mechanisms of change? My curiosity led me to study a lot of neuroscientific literature and one day I came across a seminal paper by Karim Nader titled ‘Memory traces unbound’. This paper showed that it was possible to erase fear memories in animals by using a new insight called memory reconsolidation, which refers to the intrinsically dynamic nature of memory. Further research showed that this process is possible in specific settings in which something new can be learned or in situations where the organism experiences a match-mismatch between what has been learned and the actual situation, and that under such circumstances the memory trace actually ‘opens up’ as it were. When this happens, similar processes take place, such as the synthesis of protein, as those that occur when a fear comes into being.  

Armed with the knowledge that protein synthesis plays a large role in the formation of a fear and that it can be blocked, we shifted our focus to the use of propranolol, a noradrenergic beta blocker. In 2007 I received a Vici grant which further spurred my research and enabled me to create a lab and start conducting the first human trials. My initial research into its use in conjunction with memory retrieval yielded promising data, including a series of replications and extensions. Since then we have booked good results in people with arachnophobia and at the moment we’re busy with a pilot on people with panic and posttraumatic stress disorders.  

What exactly happens during memory reconsolidation?

The memory trace opens up when the fear memory is triggered, say by exposing subjects with arachnophobia to spiders. Once this happens, we have a specific time frame in which to administer propranolol, which blocks the beta-adrenergic receptors in the brain through which noradrenaline is released. This in turn plays a role in a number of steps and in the synthesis of protein, which is now blocked. The pill itself is only taken once. When the subjects we have treated return in the period after the memory retrieval session, usually between a few days and three months later, the fear has disappeared and doesn’t return, as opposed to extinction. 

It is important to note that during memory reconsolidation the emotional memory is erased but patients still continue to have ‘cold cognition’, i.e. remember what happened and how they felt. The curious thing, though, is that their behaviour is the first to change and only then their cognition. This is in contrast to traditional cognitive behavioural therapy whereby people first start thinking differently before a change in behaviour occurs. In our tests on people with arachnophobia, for example, the subjects who returned after treatment still felt nervous when asked to touch a picture of a spider, but admitted that their nervousness was different and that they have more confidence. It is almost as if their autobiographical memory still has to adapt to the fact that the physical fear response has vanished.

Is it presumptuous to state that your use of propranolol might bring the curtain down on established therapies such as CBT?

I wouldn’t venture that far yet. What I do know is that propranolol only works in conjunction with the process of memory reconsolidation. Just taking the pill itself won’t have any effect. We’ve done double blind experiments in three different situations (one with reactivation and placebo, one with only propranolol and one with a combination of reactivation and propranolol) and only memory reactivation with propranolol  produces the loss of a specific fear.

When it does succeed, however, the treatment is more effective and more rigorous than traditional therapy. It is also less invasive and the use of propranolol only a one-off, as opposed to established anti-anxiety meds that need to be taken regularly and pose risks in terms of addiction and withdrawal.   

How long until you start with a large scale roll-out?

We’re still in the preliminary stage at the moment. Once the tests we’re currently doing turn out successful, we’ll be able to start thinking about a larger roll-out of the therapy. The jump from animal testing to randomised control trials sometimes happen too quickly, and as a result one misses a number of crucial steps. This is why we are still doing various pilots. If all goes well, however, we’ll be ready to make the treatment available in the coming years.

Published by  UvA Persvoorlichting

11 January 2016