Understanding Anxiety disorders: Shifting paradigms

Written By Neena Joseph

Neena Joseph

Anxiety is a recognizable state of apprehension. It is a disorder when anxiety is sustained and heightened in the absence of immediate threats(2). In other words, you worry too much for too long, and uncontrollably. Anxiety does not typically arise from real or imminent threats. It is usually brought on by imagined, remote or minor threats. The kind of threats that are not very specific or predictable(8).

Anxiety disorders are debilitating. They are the commonest of all psychiatric conditions.

Amygdala is a mass of grey matter located in our temporal lobes. There are two of them, each hidden deep in our brain hemispheres, somewhat shaped like tiny almonds. Despite their small size, they are well-connected and has strong networks with other brain sites.

Amygdala is indispensable to mediating our emotions. It functions like a referee, detecting potential threats and alerting our defence systems into action through its robust networks. It is the key mediator of fear, anxiety, and aggression. It further oversees our add-on emotions like distrust and vigilance, rules our social and emotional decisions, kindles our automatic nervous systems and jump starts our hormonal stress responses(9).

In this blog, we’ll look closely at the experience of anxiety and uncover its key cerebral underpinnings.

Being Anxious

Anxiety becomes pathological and problematic when it stops us from doing what we want or ought to do in daily life. Imaginary threats loom out of innocuous events. Life becomes strenuous, and the worst worries often take the form of extreme anxious anticipation. Daily life is weighed down by bodily manifestations of anxiety - dry mouth, pounding heart, sweaty palms, shaking or hyperventilation. Our alarm bells are ringing wild in the absence of actual threats, defenses are super activated, and the body is ready to fight, flight or freeze.

Relief from anxiety is often sought in escape or avoidance. The sufferers may also resort to other means, leading to dependence on various kinds of ‘chill pills’ or usually alcohol. In extreme cases, anxiety may lead to phobia, confining sufferers to their homes.

The instinctive solution is to avoid the specific situations that trigger too much anxiety. In reality, such avoidance alleviates distress short-term, but aggravates it long-term. Avoidance merely perpetuates anxiety and compounds disability in the sufferer.

Anxiety disorders must be recognized early. Judicious use of antianxiety medications and Cognitive Behavior Therapy is often the first resort. However, this may not always be optimal for all, and many suffer lifelong symptoms, their individual potential unrealized and leading to a sense of failure.

What do we know about Amygdala?

It is useful to understand what really happens in our brains when we are anxious — the inner talk of our neurons. How does brain interpret and signal these threats? How are the defenses activated? Which neurons are firing, how are they talking, and with whom?

Amygdala takes the center stage in this matrix. It communicates back & forth with the prefrontal cortex — The executive center where our minds do the reasoning and thinking(1,2,6). It is further connected to hippocampus (we store memories here) as well as automatic sympathetic nervous system (automatic functioning of heart, lungs, stomach etc.). These connections of amygdala are vital in spreading its influence on hypothalamus (related to stress hormones) and brainstem (arousal and automatic responses to fear).

Down to the specific pathways in amygdala, its functions are understood to be spilt. Activation of certain pathways in amygdala churn up positive feelings and open behaviors to that of exploration and approach. Conversely, the other pathways stir up negative emotions and avoidance. This is remarkably specific. Those with anxiety disorders are understood to have problems in the way these parts talk to each other(3).

Can we target amygdala to treat anxiety?

Many scientific studies on lab rats tell us amygdala can be a crucial site for direct brain therapy in anxiety. The research in this area is advancing fast and preliminary results say this may become a reality in the not too distant future.

An excellent illustration of amygdala-anxiety connection comes from a study of lab mice by Tye and her colleagues (2011). A mouse can’t speak its feelings, but this can be read in its behaviors. In order to test mouse-anxiety in a lab, a maze was set up with open and closed areas. You then observe how a mouse behaves to infer its feelings — Is it freely exploring or withdrawing?

This study pioneered the use of ‘optogenetics’ to study ‘feelings’ through experiments on the amygdala — light-sensitive parts of algae are cloned and genetically engineered to create light-sensitive neurons in the mouse-amygdala. Next, you control how this particular group of nerve cells fire, how they talk to each other by simply flipping a light switch on and off (2,3). Applying optogenetics, they were able to activate or inhibit specific projections in the amygdala of a mouse. ‘Switched on’ mouse explored freely while ‘switched off’ mouse hid in the corner(3). These behaviors were immediate and reversible. This proves that amygdala can be directly manipulated to control anxiety levels(2,3).

Amygdala-prefrontal connection is quite dynamic. Anomalies in these connections are observed in pathological anxiety(1). The integrity of this partnership is detrimental to our ability to regulate anxiety and fears. At a time of acute anxiety, this partnership breaks down, and our reactions default to reflex like automatic reactions. Remember, our reactions are not voluntary at this time(7). Capacity for self-regulation is temporarily arrested.

A potentially useful intervention for anxiety therefore is to modulate this amygdala-prefrontal pair with thoughts and relaxation skills. Reasoning with positive thoughts is a top-down approach, while muscle relaxation is a bottom-up anxiety management strategy. Simply stated, a strong amygdala-prefrontal connection can decrease your anxiety and a weak amygdala-prefrontal connection can increase your anxiety(1).

A promising study in human subjects for potential treatment of social anxiety (disabling anxiety in a range social situations) using nasally administered oxytocin (a hormone related to social bonding and attachment) was recently published in Nature. This intervention was again aimed at amygdala(4,12).

Neurofeedback is an upcoming field in psychiatric treatment. Here patients can visualize their brain pathways in real time and receive explicit feedback of their own brain activity. You can watch your brain in action. This may give one the power to alter the firing tracks of neurons by merely changing one’s thoughts. The latest results from neurofeedback studies are promising, benefitted big time with the invent of real-time functional magnetic resonance imaging of specific tracks in brain, that is, 'real-time’ brain feedback (10,11,12,13).

Novel studies now focus on brain-based interventions to help relieve symptoms of anxiety. We are privier to the workings of our brains, how it creates our emotions, deals with changes, and remains plastic while we are going about our daily lives. Potential treatments for anxiety are moving beyond medications and Cognitive Behavior Therapy, integrating the established with the new, setting new trends. The day may come when we are able to control our own amygdala and regulate our anxiety for better outcomes.

References

  1. Kim, J., Loucks, R. et al. Volume 223, Issue 2, 1 October 2011, Pages 403-410. [https://doi.org/10.1016/j.bbr.2011.04.025][0]
  2. Tye, K., Prakash, R., Kim, S. et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471, 358–362 (2011). [https://doi.org/10.1038/nature09820][1]
  3. Kay M. Tye/TED@NAS. What investigating neural pathways can reveal about mental health. [https://www.ted.com/talks/kay_m_tye_what_investigating_neural_pathways_can_reveal_about_mental_health?utm_campaign=tedspread&utm_medium=referral&utm_source=tedcomshare][2]
  4. Labuschagne, I., Phan, K., Wood, A. et al. Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder. Neuropsychopharmacology 35, 2403–2413 (2010). [https://doi.org/10.1038/npp.2010.123][3]
  5. Davidson, R. Anxiety and affective style: role of prefrontal cortex and amygdala. Volume 51, Issue 1, 1 January 2002, Pages 68-80
  6. M. Justin Kim and Paul J. Whalen. The Structural Integrity of an Amygdala–Prefrontal Pathway Predicts Trait Anxiety. Journal of Neuroscience 16 September 2009, 29 (37) 11614-11618; DOI: [https://doi.org/10.1523/JNEUROSCI.2335-09.2009][4]
  7. M. Justin Kim, Dylan G. Gee, Rebecca A. Loucks, F. Caroline Davis, Paul J. Whalen, Anxiety Dissociates Dorsal and Ventral Medial Prefrontal Cortex Functional Connectivity with the Amygdala at Rest, Cerebral Cortex, Volume 21, Issue 7, July 2011, Pages 1667–1673, [https://doi.org/10.1093/cercor/bhq237][5]
  8. Davis, M., Walker, D., Miles, L. et al. Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety. Neuropsychopharmacology.35, 105–135 (2010). [https://doi.org/10.1038/npp.2009.109][6]
  9. Sapolsky, R. M. Behave: the biology of humans at our best and worst. New York, New York: Penguin Press.30-43 (2017).
  10. Zilverstand, A., Sorger, B., Sarkheil, P et al. fMRI neurofeedback facilitates anxiety regulation in females with spider phobia.Front.Behav.Neurosci.,08 June 2015| [https://doi.org/10.3389/fnbeh.2015.00148][7]
  11. Scheinost, D., Stoica, T., Saksa, J. et al. Orbitofrontal cortex neurofeedback produces lasting changes in contamination anxiety and resting-state connectivity.Transl Psychiatry 3, e250 (2013). [https://doi.org/10.1038/tp.2013.24][8]
  12. Wikipedia. [https://en.wikipedia.org/wiki/Oxytocin][9]
Neena Joseph http://www.aucklandpsychiatrist.com