The ZRT Laboratory Blog

PTSD and the Resilient Brain: A Symphony of Neurotransmitters and Hormones

Fri, 26 Jan 2018 12:37:00 -0800

Traumatic stressors are defined by the direct experience, witnessing of, or confrontation by an event involving actual or threatened danger, and they evoke responses that include intense fear, helplessness or horror. On a national and global level 2017 was peppered with one disaster after another. There has been a palpable sort of post-traumatic stress permeating the nation. On the heels of the catastrophic storms, life-altering fires and manmade events, re-visiting what allows some people to bounce back more quickly than others after trauma may shed light on important, emergent assessment criteria.

More and more research has identified the alterations that stress hormones and neurotransmitters impose on brain development. In a series of revolutionary experiments, associate professor of integrative biology Daniela Kaufer, UC Berkeley, and her colleagues, discovered that chronic stress and elevated levels of cortisol can generate more overproduction of myelin-producing cells and fewer neurons than normal. Kaufer et al. published their findings in the February 11, 2014 issue of the journal Molecular Psychiatry [1]. Severe stress reactions can produce a series of neurological changes that affect the structure and function of the HPA axis and critical brain regions. These findings might provide an explanation for how chronic stress can also affect learning and memory.

As with many mood disorders, a multi-modal approach to treatment often yields the best outcomes. PTSD is no different in the sense that resolution or modification of this anxiety disorder relies on a combination of proper assessment and management. Understanding the impact of PTSD at a neurobiological level has relevance in personalizing treatment of this condition. Proper testing to evaluate neurochemistry and hormones can offer an advantage in both assessment and more targeted treatment options.

Stress

The Sympathetic Nervous System and HPA axis are both activated as part of the stress response and work in concert to promote adaptation, or allostasis, by enabling organisms to adapt to changing conditions in their environment [2]. In considering the neuro-endo cascade as it relates to high stress, we often consider the big players to be cortisol, norepinephrine, and epinephrine. During stress and trauma, the “fight or flight” response is activated - epinephrine increases your heart rate so you can move fast. Norepinephrine sends blood to large muscle groups and the lungs, and pupils dilate. Cortisol is released, which over time suppresses the immune system. Emotions intensify and, as the limbic and endocrine systems go into full speed, the executive functioning of your brain decreases (frontal lobe blur), and the reptilian brain takes over.

Small but Mighty!

Key brain regions get flooded with signals from hormones and neurotransmitters. Two critical areas of the brain that manage the incoming stressor and cascade of hormones (and neurotransmitters) are the hippocampus and the amygdala. Small but mighty, the amygdala is amazingly powerful. When amygdala neurons fire intensely, a physical stress response is triggered in the body. After the amygdala sends a distress signal, the hypothalamus activates the sympathetic nervous system by sending signals to the adrenal glands. Conditions such as anxiety, depression, post-traumatic stress disorder, and phobias have been linked to abnormal functioning of the amygdala. The amygdala orchestrates the fear/emotional response to an experience and sends signals to the brain stem. During this "survival trigger" the prefrontal cortex (executive function) is bypassed.

The evolving research on PTSD reveals its complexity and system-wide effects. Supporting the inhibitory and HPA systems and managing excitatory overdrive are critical cornerstones of treatment. It has been suggested that alterations in norepinephrine, epinephrine, and serotonin may have relevance for symptoms commonly seen in survivors of trauma who have PTSD, including hypervigilance, exaggerated startle, irritability, impulsivity, aggression, intrusive memories, depressed mood, and suicidality [3].

Key Markers in Assessment:

Cortisol

Cortisol is prototypically the stress hormone as both physical and psychological stress leads to cortisol elevation in the blood and brain [4]. Yet the relationship of cortisol to PTSD has been varied. Early work with people who had survived years after extensive chronic trauma in the Holocaust found that they had lower than normal cortisol levels [5]. This was a paradox as trauma elevates cortisol, but it now seems that this low level may either reflect some compensatory response to the elevated cortisol at the time of the trauma or be a phenotype that assists people in resisting the effects of stress. Studies of acute trauma show elevations of cortisol [6], and that higher plasma cortisol correlates with symptoms of PTSD [7].

Diurnal Epinephrine and Norepinephrine

Cortisol alone was not as predictive as the combination of norepinephrine to cortisol levels in defining PTSD.

In many of the findings the levels of norepinephrine in relation to cortisol proved important. Cortisol alone was not as predictive as the combination of norepinephrine to cortisol levels in defining PTSD. From the research, it appears that low cortisol levels, together with high catecholamines, may reflect a late event in the natural history of the disorder, months or years after the trauma [8].

Across a lifespan, the continued ability to respond to stress appropriately is a critical component to maintaining optimal health [9][10][11].

Because of its multiple roles in regulating arousal and autonomic stress responses, as well as promoting the encoding of emotional memories, norepinephrine has been a central focus of many studies investigating the pathophysiology of PTSD [12].

Cortisol in Relation to Norepinephrine, Epinephrine

Evaluating the diurnal rhythms of epinephrine and norepinephrine, along with the circadian rhythm of cortisol, may help identify specific imbalances in an individual’s response to stress, and how the body adjusts sympathetic nervous system parameters accordingly. (- Kate Placzek)

With the refinement of diurnal neurotransmitter testing and hormones testing there is now a way to measure markers, which gives insight into the biology of an individual’s system-wide response to trauma.

This lends encouragement for exploring multivariant strategies, using hormonal ratios, in an effort to increase the diagnostic sensitivity of neuroendocrine criteria in the assessment of psychiatric patients [13].

Glutamate

Glutamate is the major excitatory neurotransmitter in the brain and a key neurotransmitter in memory formation. It plays a crucial role in the human stress response and probably in the pathophysiology of PTSD. Release of glutamate leads to the long-term changes in synaptic plasticity that ensure memory is encoded, whereas GABA receptor activation inhibits this, which is why benzodiazepines lead to amnesia. Other neurotransmitters, especially noradrenaline, may also play a facilitatory role, especially in traumatic memories [14].

GABA

GABA is the brain's major inhibitory neurotransmitter. It suppresses stress-induced actions of the amygdala. GABA receptors within the amygdala inhibit glutamatergic excitation.

Serotonin

The serotonergic system has important interactions with the adrenergic, glutaminergic, GABA, and dopamine systems. There also appears to be a synergistic interaction between 5-HT-1-A and GABA receptors with regard to acute stress and PTSD. Research supports that SSRIs and serotonin support may be just one component/consideration of PTSD treatment.

Dopamine (DA)

During uncontrollable stress, amygdala activation produces prefrontal cortex dopamine release. Whether or not DA metabolism is altered in PTSD remains unclear, though genetic variations in the DA system have been implicated in moderating risk for PTSD [12].

The Good News

Human beings are more than just the working of our automatic brain, and volumes of research support that the power of neuroplasticity makes it possible to change brain structure and function throughout your lifespan. The brain circuits, while influenced by our early experiences, are capable of changing throughout our lives. Mindset, behaviors and stress are never fixed. In addition to neurobiological considerations, building resilience during times of stress, natural disasters and life-altering events is critical. As we welcome in a New Year let’s remember that a sense of community, personal support systems, proper sleep, nutrition, regular exercise and individual assessment of our stress response can all empower us to better withstand more critical times of stress.

Related Resources

References

[1] Chetty S, et al. Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. Mol Psychiatry. 2014;19(12):1275-1283.

[2] McEwen BS, Seeman T. Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci. 1999;896:30-47.

[3] Southwick M, et al. Neurotransmitter alterations in PTSD: Catecholamines and serotonin. Seminars in Clinical Neuropsychiatry, 4, 242-248. Seminars in clinical neuropsychiatry. 1999; 4:242-8.

[4] Droste SK, et al. Corticosterone levels in the brain show a distinct ultradian rhythm but a delayed response to forced swim stress. Endocrinology. 2008;149(7):3244-53.

[5] Yehuda R, et al. Low cortisol and risk for PTSD in adult offspring of holocaust survivors. Am J Psychiatry. 2000;157(8):1252-9.

[6] Fukuda S, et al. Effect of the Hanshin-Awaji earthquake on posttraumatic stress, lifestyle changes, and cortisol levels of victims. Arch Environ Health. 2000;55(2):121-5.

[7] Maes M, et al. Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia. Acta Psychiatr Scand. 1998;98(4):328-35.

[8] Pervanidou P, et al. The immediate and long-term impact of physical and/or emotional stress from motor vehicle accidents on circulating stress hormones and adipo-cytokines in children and adolescents. Stress. 2008;11(6):438-47.

[9] Yehuda R, et al. Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. J Nerv Ment Dis 1992;180: 321–325.

[10] Southwick SM, et al. Neurotransmitter alterations in PTSD: catecholamines and serotonin. Semin Clin Neuropsychiatry 1999;4:242-8.

[11] Yehuda R. Biology of posttraumatic stress disorder. J Clin Psychiatry 2001;62: 41–46.

[12] Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma Dialogues Clin Neurosci. 2011; 13: 263–278.

[13] Mason JW, et al. Elevation of urinary norepinephrine/cortisol ratio in posttraumatic stress disorder. J Nerv Ment Dis. 1988;176:498-502.

[14] Nutt DJ. The psychobiology of posttraumatic stress disorder. J Clin Psychiatry. 2000;61 Suppl 5:24-9; discussion 30-2.

Holiday Health: The Food & Mood Connections

Fri, 18 Nov 2016 08:31:00 -0800

With the holidays ahead, it is an important time to take a closer look at the stress response, food and mood. The holidays, for many, can trigger stress and food behaviors that set off a cascade of hormones and neurochemicals.

The emotional stress that the holidays can elicit for many people, paired with the excess foods and libations that abound, can set us up for trouble. Understanding the neurochemical response to certain foods can help us better navigate our foods and mood this holiday season.

Hooked

Many people complain about "holiday weight" gain. Not surprisingly, the week of New Year’s is the time of year that fitness clubs report their strongest upswing in membership. So is it possible to navigate the holiday season with less pudge, better sleep and less stress? Absolutely!

Over the past decade the topic of addictive food misuse has steadily become more prevalent in the media. With the obesity epidemic in our nation (approximately 37% of the U.S. adult population), the addictive, brain-chemical-altering effects of sugar, salt and high fat foods are important areas to understand and address. How have these foods affected us and kept us addicted to the substances in them that impact our mood and health?

In addition to considering key neurochemicals that certain foods can elicit, "comfort foods" can put the brakes on stress by affecting the glucocorticoid feedback system (HPA axis). Fats, for instance, can quell cortisol (a key stress hormone produced by the adrenal glands). Research supports that chronically elevated glucocorticoids can lead to the tendency for poor food choices (sugars and fats especially) and even drug seeking behaviors. With nearly two-thirds of Americans being overweight, the epidemic of food addiction resulting in metabolic issues is creating a health crisis. Solutions need to consider food intake, energy output and stress-reducing behavior modification.

A Spoonful of Sugar

Over the years, the medical community has gained a deeper understanding of dopamine and its relationship to food disorders, drug use, sexual addictions and ADD/ADHD. Foods signal pleasure through the substances that they contain, which set off a series of biological events in the body and brain. Three key areas of the brain that are activated and affected are the ventral tegmental area (VTA), the prefrontal cortex (PFC) and the nucleus accumbens (NAc). These areas of the brain are tied to motivation, reward and reinforcement learning. The VTA and NAc are all deep brain regions where dopamine is very active. One of the biggest triggers in brain dopamine is sugar. It is clear from the studies that glucose causes dopamine to double in certain areas of the brain. Sugar is a powerful substance that is in ample supply during the holidays!

The good news is that through novel testing, it is possible to gauge how the neuro-hormone system is running.

The conversation about food and pleasure-seeking behaviors would be shortchanged without considering the teenage brain as an example of how the brain can get "high-jacked." Teens are especially prone to dysregulated behaviors as their executive centers of the brain (PFC) are still in development. The teenage brain is dominated by the amygdala and the NAc (which is above a key dopamine center). This has been looked at as one physiological explanation for why teens are susceptible to unhealthy relationships with both food and drugs. This biological fact paired with our food environment, which has changed dramatically as companies “enhance” (to increase sales) and modify food (adding sugar which blasts dopamine), reveals a clear relationship for how the developing brain is susceptible to getting "hooked." So the earlier we intervene, the better.

The good news is that through novel testing, it is possible to gauge how the neuro-hormone system is running. The ability to look at dopamine levels, and importantly dopamine metabolite levels, can give indications of imbalances and offer clues to effective interventions.

Holiday Stress

We are wired to tolerate short bursts of stress. Excess levels, over long periods, can dysregulate neurotransmitters such as serotonin and dopamine, and hormones such as cortisol. The holidays for many can raise stress and impact the cortisol response. The HPA axis regulates the cortisol response and is the body’s biological attempt to modulate stress. Yet "switched on" for too long and we begin to store fat and negatively impact neurotransmitters and hormones.

In addition to effects that stress elicits on neurochemicals and hormones, calorie-laden and nutrient-light (high sugar, high “bad” fats) food choices disrupt balance as well. We are designed for small blasts of stress like running from a bear in the woods, hiding from lions or even hosting Thanksgiving! Chronic stress and exposure to stressors during the early years of life set the stage for a brain that can become wired for addiction to drugs, foods and behaviors. The fight-or-flight system, under constant demand, will disrupt the connection between the stress centers of the brain and the frontal lobe. Akin to a broken signal light at a busy intersection, having the brain on "red alert" constantly disrupts grey and white matter ratios in the brain and sets up potential lifelong patterns for addiction and mood disorders. The good news is that the brain is malleable and neuroplasticity is real. The brain can shift throughout life.

The Calm Turkey

We cannot discuss food and mood at this time of year without including our upcoming Thanksgiving turkey rituals. Tryptophan, an amino acid found in many foods, is often viewed as the source of our post-meal lethargy. It is true that turkey does contain an ample source of tryptophan (yet no more than other poultry). Therefore we cannot simply look to the turkey as the reason for the surge in post-meal calm. Likely it is the symphony of insulin and carbohydrates that assists the free form of tryptophan in making its way across our blood-brain barrier. Without the insulin blast from those mashed potatoes or pie, a small percentage of dietary tryptophan would be battling it out in the blood stream with other competitive amino acids trying to make their journey across the blood-brain barrier.

So if you want to get the post-dinner sleepy effect of that Thanksgiving turkey, eating some of those carbs may be just the thing to do. For individuals with metabolic issues it is not a simple equation and I am not proposing a high sugar diet to manage mood. Mindfully indulge in some potatoes with your Thanksgiving turkey, it will assist in the serotonin-bliss-state. But skip the sugary desserts that could set off a glycemic response.

This holiday season practice mental, physical and emotional hygiene by giving gratitude, breathing deeply, getting adequate rest, balancing work-life demands and taking time in nature to recharge your system. Remember that managing stress is proven to have lasting and positive effects on both neurotransmitters and hormones!