15 Sep Specific Brain Circuit Permanently Switched On In Patients With Anxiety Disorders
MedicalResearch.com Interview with:
Dr Oliver J Robinson Ph.D.
Section on Neurobiology of Fear and Anxiety,
National Institute of Mental Health, NIH, Bethesda, MD,
Institute of Cognitive Neuroscience
University College London, London, UK
Medical Research: What are the main findings of the study?
Dr. Robinson: This study is looking at a symptom of anxiety disorders known as “negative affective bias”. This describes the tendency of people with anxiety disorders to focus on negative or threatening information at the expense of positive information.
We completed a number of previous studies looking at so called “adaptive” anxiety in healthy individuals – this is the normal, everyday anxiety that everyone experiences; walking home in the dark, for instance (in these prior studies we used unpredictable electrical shocks to make people anxious and stressed). When we made healthy people transiently anxious in this way we showed that this was also associated with negative affective bias and driven by a specific brain circuit: the dorsal medial prefrontal (anterior cingulate) cortex—amygdala aversive amplification circuit.
In this study we showed that the same circuit that was engaged by transient anxiety in our healthy sample was actually engaged ‘at baseline’ (i.e. without stress) in our patient group. This suggests that this mechanism which can be temporarily activated in healthy controls becomes permanently ‘switched on’ in our patient group. This might explain why people with anxiety disorders show persistent ‘negative affective biases’.
Furthermore, the extent to which this circuit was turned on correlated with self-reported anxiety. That is to say the more anxious an individual said they were, the greater the activity in this circuit. Therefore, there seems to be more of a dimension or scale of anxiety, rather than a simple well/unwell diagnosis.
Medical Research: Were any of the findings unexpected?
Dr. Robinson: This was part of a programmatic sequence of studies following up from healthy control studies. As such our findings were as hypothesized. However, the idea that the same mechanism might be involved in so called healthy anxiety and anxiety disorders may be surprising to many (given how different the two experiences can be).
Medical Research: What should clinicians and patients take away from your report?
Dr. Robinson: The first thing to note is that this will not actually have an immediate effect. It will need to be replicated and a number of follow up studies are needed. However, one key thing is that we have previously shown that this circuit is modulated by serotonin. Specifically, if you lower serotonin in healthy individuals using a dietary manipulation, you actually see increase in activity of this circuit – in the same way that it is recruited in patients. This suggests that serotonin may be involved in ‘inhibiting’ this so called ‘aversive amplification circuit’. As such, selective serotonin reuptake inhibitors (SSRIs – the first line pharmacological treatment for anxiety disorders e.g prozac) may work by dampening down and restoring balance in this circuit. This is important, firstly because – surprising as it may be – we do not actually know how these drugs work. At the moment for the majority of people with a mood or anxiety disorder, the first treatment they try does not work. Anything we can do to improve this hit rate would be enormously beneficial. It would avoid unnecessary suffering and wasted time.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Robinson: Firstly, we need to replicate these findings. I am currently about to explore this same circuit in people with depression – who also show negative biases – to see if this mechanism may cut across diagnoses. We are also going to directly look at the effects of SSRIs on this circuit and see if it is possible to start using this technique to stratify patients into those who will respond to SSRIs and those who wont. Ultimately can we use this understanding to improve the diagnosis and treatment of anxiety disorders, because at the end of the day that is all that matters. Can we improve the lives of people who suffer from these problems? Can we translate this to clinical relevance?
Citation:
Dr Oliver J Robinson PhD,Marissa Krimsky BA,Lynne Lieberman BA,Phillip Allen BA,Katherine Vytal PhD,Christian Grillon PhD
The Lancet Psychiatry – 1 September 2014 ( Vol. 1, Issue 4, Pages 294-302 )
DOI: 10.1016/S2215-0366(14)70305-0
| Sep 2014 | The Lancet Psychiatry, Vol. 1 No. 4 pp 294-30 |
Last Updated on September 15, 2014 by Marie Benz MD FAAD