by Carolyn Lacey, 24 June 2015
I am stressed out of my mind. Isn't this phrase something you hear, or even say, often? Our brains are essential to our perception and our response to stress, protecting us from harm via the so-called fight-or-flight response. In short bursts our brains do a pretty good job of this, but long-term or chronic stress, can manifest itself as severe mental health disorders such as depression, post-traumatic stress disorder (PTSD) or addiction. The statistics about how much these "problems" cost society are readily available so I don't feel the need to quote them here as, ultimately, the greatest cost is to the individual and their families. I am, however, going to highlight an interesting research article that was published earlier this month concerning chronic stress in Nature Neuroscience led by Daniel Christoffel in Scott Russo's group at Mount Sinai, New York, and discuss how their research might help us manage chronic stress and keep stress out of our minds.
When it comes to enduring chronic stress, people are typically split into two broad groups: those who "cope" and those who don't. Those who have brains that are wired to cope with chronic stress are known as "resilient". Those not quite so lucky will eventually (depending on their threshold) develop other mental health disorders ("susceptible"). This variability in the brain response to chronic stress found in humans is also found in mice. Some mice are resilient to stress and others suffer depression-like symptoms. Researchers take advantage of this to study the effects of chronic stress on the brain. Like humans, different mice have different "personalities" and Daniel Christoffel took a strain of mouse known for its gentler disposition and put it in a cage with a mouse from a more aggressive p ersonality strain. To make matters worse, after the short exposure to the aggressive mouse, the gentler mouse is "protected" from the aggressive mouse only by a screen. This test, implemented over many days, is known as "chronic social defeat stress" and leads to increased social avoidance and other depression-like behaviour. What makes this a cool model is that just like in humans, all of the gentle mice experience acute physiological stress responses (increased heart rate etc.) but only a proportion of those mice will develop depression-like symptoms. By comparing these two groups of mice, neuroscientists can gain a better understanding of what causes deleterious effects of chronic stress and, moreover, hijack the "safety" mechanisms shown by the brains of those who don't.
One of the brain areas suggested to play a pivotal role in developing depression-like symptoms following chronic stress is the ventral striatum (part of the brain's limbic or "emotional" system). Massive input to the ventral striatum comes from brain areas containing dopamine (the "reward" neurochemical), the cortex (complex behaviors such as decision making, social interaction) and the thalamus (important for processing sensory information, arousal and sleep). Although the role of the dopamine system and the cortex have been well-documented in all kinds of mental health disorders (including depression and PTSD), the role of the thalamus in mental health disorders is not well-documented. Daniel Christoffel and team took advantage of virus and optogenetic technology (see this video http://mit.tv/A1bkSr for more information on this technique) and found something surprising: it was the input from the thalamus that caused the gentle mouse to become depressed after chronic stress. Simply, activating the thalamic circuit caused increased social avoidance (more susceptible) and inactivating it caused less social avoidance (more resilient). Even more incredible, this thalamic-led reaction to chronic stress caused changes in the striatum (long-term structural changes or "plasticity" leading to long-term behaviour changes). Manipulations of the cortical input had minimal, if any, effect on this depression-like behavior. Thus the thalamic input to striatum is key to understanding why some people are "resilient" to the effects of chronic stress. A role for the thalamus in controlling mental health is groundbreaking.
But, for now, what does this mean for chronic stress sufferers? Let me hypothesize a little. Mental health problems, such as depression and PTSD, are tackled with pharmaceutical- and psychological-based therapy. The thalamic nuclei that provide input to the striatum discussed above are exceptionally important for arousal, attention, pain processing, and consciousness (indeed, lesions lead to coma). They mediate conversation between parts of the brain that respond to direct input from the environment and the parts that make the decisions on how to respond, navigating what is important to respond to and what isn't (in this case the gentler mouse was in potential danger while in the same cage as the aggressive mouse but not when it was behind a screen). Part of being resilient to the effects of chronic stress is how our brains perceive the stressor and part of stress management is teaching our brains to understand what is a real stressor. Therapies such as Cognitive Behavioral Therapy (CBT) and Mindfulness-Based Stress Reduction (MBSR) are proving to be successful for managing response to chronic stress and its co-conspirators. Thus, by moderating what will be perceived a stressor by the thalamus, one might pro-actively be keeping stress out of your mind. Being susceptible to the effects of chronic stress is potentially manageable. So in my opinion, this paper is exciting as not only can it open new doors through the thalamus to understand why chronic stress can lead to other mental health disorders, but it also opens doors to a system that might directly help the way professionals treat sufferers, through new pharmaceuticals or behavioural therapies. The thalamus (an area of expertise of Neurexpert co-founders http://doi.org/10.1016/j.neuropharm.2014.12.031) will likely be a future hotspot for research into mental health disorders related to chronic stress (including PTSD).
To view the original paper discussed in this blog, "Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress" in Nature Neuroscience please click here.