Anxiety, Nutrition, and the Brain

by Vanessa Chiarello, UofT Undergraduate Student in Neuroscience and Blogger for CAN

One minute you feel fine; the next, you are in a frantic frenzy. Just like the calm before a storm, you seem ok but then lightning strikes, creating havoc in the emotion-linked neural pathways of your brain.  

This is panic. This is fear. 

This is anxiety: a sudden physiological response, or a sensation, of extreme fear or worry, that is felt within your body and that consumes every inch of your mind.
To explain anxiety further, let’s start with an example: It’s the first day of the semester. Walking into your calculus class, you think to yourself “Sure, I never learned calculus before and high school math was over two years ago, but I got this. It’s going to be ok.” You sit down with this optimistic mindset. You open your notebook, take out your pen, ready to begin your notes. As you patiently await the arrival of your professor, you reassure yourself that this will be fine, and to pass the time, you start to tune into the conversations of people around you. Oops, maybe that was a bad idea. They’re talking about how they failed this course, not only once, but twice. “Oh,” you say. Somehow though, you manage to shake off that fear before it grows into something big.

“IT WILL BE OK.” Four simple words that you mentally repeat to yourself over and over again as the professor walks in. Immediately, he starts to go over the course syllabus, a typical first-day routine. But there’s an addition: he warns you that this class is fast-paced because it’s a summer course. He warns you that if you don’t do your homework or if you haven’t taken calculus before (like me), this class can quickly become your worst nightmare. He warns you that you may fail this course. Going through page by page of the outline, you suddenly feel overwhelmed. You see chapter titles that sound confusing just on their own and homework questions that seem to go on forever, and now your heart is racing. It skips a beat. Two beats. It’s fluttering. Actually, it feels like its dancing the quick-step. Thoughts of worry and regret flow through your mind at what seems like 100 miles per hour, and you cannot control them. You feel your face grow red and flushed. Has the temperature turned up? Your pen drops because you’re slightly shaking. You feel nauseas, and you can’t breathe. What’s happening to you? Unfortunately, you are experiencing an "anxiety attack."
This was me about two months ago. In what seemed like a fraction of a second, I went from cool, confident, and collected about my calculus class, to a bewildered, can’t-breathe, going to be sick “hot” mess, so to speak. This sensation, called anxiety, was my body’s physiological response to my surrounding external environment—or in other words, my reaction to my calculus professor. Not a pretty good first day, was it? So what did I do? Besides panicking, I did my research, and fortunately I found that nutrition may be a simple and effective way to help. Phew!  

LOWERING ANXIETY NATURALLY: HOW NUTRITION HELPS
Although some of us (the unlucky ones) may be more susceptible to one too many anxiety attacks, there is a way to build up our strength against them: nutrition! How can food be our antidote to anxiety? Well, a number of brain chemicals are out of balance during an anxiety attack, so the solution is to find nutrients that break down into these very important chemicals that we’re in dire need of. Serotonin is one of the major brain-calming chemicals often in deficit in those anxiety-prone people like me. An interesting experiment done on two groups of rats helps explain why serotonin is our saviour: one group had the gene for the transportation of serotonin back into neurons to be used for sending chemical messages, whereas the other group did not have this gene.  Rats of the former group not only have insufficient availability of serotonin but they also have less emotional control and anxiety-like personalities. The same holds true for human subjects. This genotype for abnormal serotonin transporter gene correlates with a hyperactive amygdala, an area of the brain known for its role in processing fear and other emotions. This abnormality seems to lead to lower stress resilience (i.e., inability to cope or “bounce back” after stress). To further test how a low or high level of 5-HT transportation contributes to anxiety, researches fed the two groups of rats a specific diet of polyunsaturated fatty acids (PUFAs), B vitamins, and phospholipids (soy lethicin): three nutrients shown to decrease anxiety (especially PUFAs). When rats with low serotonin transporter activity were fed a regular diet not rich in the three key nutrients mentioned above they displayed higher anxiety-related behaviour and could not stop their fear response. However, these effects reversed when rats with the same low serotonin were fed a diet rich in the nutrients. In other words, with the specific diet, rats’ anxiety behaviours were reduced! The diet did nothing to rats that had normal functioning serotonin, however, showing that diet has therapeutic benefits only when animals were genetically compromised. 

B vitamins exhibit most of their benefits by elevating mood (i.e., are sometimes used as anti-depressants), which may also help anxiety by contributing to a “feel good” mood. PUFAs increase some serotonin receptors, which make binding of serotonin more efficient and increases serotonin levels in the brain. This leads to decreased anxiety. Other brain chemicals often deficient in anxiety-prone people are GABA (the brains biggest calming chemical), magnesium (prevents against substance P toxicity), potassium (not enough allows too much sodium to enter channels in the brain causing an “overactive, over electrified, anxious” brain), taurine (enhances GABA effects), estrodial (enhances serotonin receptivity), and progesterone (converts into a compound that activates GABA). On the other hand, excess dopamine and glutamate (the brain’s stimulating neurochemicals), as well as histamine (a chemical that activates dopamine receptors) and caffeine can lead to a more anxious, over stimulated brain. In summary, the problem is easily solved at least from a neurochemical perspective: boost your levels of these calming compounds, and avoid the stimulants!

BRAIN CALMING FOODS
So what do we include in our daily diets to calm our brains? Let’s start with polyunsaturated fatty acids first since they seemed to work well for the rodents in the described experiment. Foods high in polyunsaturated fats include vegetable oils (soy, coconut, corn, safflower, and fish oil), fatty fish (salmon, mackerel, herring, and trout), and some nuts and seeds such as walnuts and sunflower seeds. Another bonus of foods high in PUFAs: they are great for your heart! 

Now let’s move onto serotonin foods. The key fact to remember is that no food source contains serotonin directly. Serotonin is derived from the essential amino acid tryptophan (L-tryptophan). Amino acids can be thought of as the “building blocks” of proteins, and tryptophan is considered “essential” because the body cannot make this compound on its own—it has to be derived from your diet. Tryptophan is a key ingredient in several protein rich foods and is the only direct substance that can convert into serotonin. It does this through a two step process: first tryptophan is converted into a chemical called 5-HTP which then converts into serotonin. So if you want to increase your serotonin, its food high in tryptophan that you need to be on the look-out for. Some of these foods include: tofu and most soy products, black-eyed peas, walnuts, almonds, sesame seeds, roasted pumpkin seeds, complex carbohydrates (whole wheat bread, brown rice, and quinoa), poultry (chicken and turkey), seafood, and low fat dairy. Another bonus of tryptophan is that it helps produce Vitamin B3 (niacin), another vitamin (as the rodent experiment also showed) that helps create a healthy mood. 

This brings us to the B vitamins, which are found in a variety of foods such as dark leafy green vegetables, fortified cereals, almonds and peanuts, asparagus, dairy products, legumes, poultry, bananas, seafood and avocados (just to name a few). Now how about GABA? Some of the foods that naturally help increase levels of GABA in the brain are shrimp, brown rice, hummus, olive oil, cherry tomatoes, and kefir. Did you know that B vitamins and magnesium are needed for GABA to be converted from its precursor? See how everything is all connected! This hopefully shows how one item out of balance can produce a domino effect on the brain. Foods high in magnesium and potassium have all been mentioned above with the additions of dried fruits and dark chocolate (for magnesium) and cruciferous vegetables like broccoli and brussel sprouts, potatoes, squash, and mushrooms (for potassium). As for sugary foods and drinks, processed foods, refined carbohydrates, caffeine, and alcohol—stay away! These foods trigger anxiety (and a depressed mood). So if you want to lower your anxiety (or depression) naturally, it’s time to start eating the right foods that will give you a healthy, calm mind and spirit.

As my very own calculus professor said, "If you come to write your test and you get anxiety, you know when your palms begin to sweat and you get clammy, and now you know nothing? Well, if you do that, then you have no hope." I think what he was trying to say was that anxiety can have a widespread affect, not only interfering with our biochemistry but also with the outcomes of our situations. What is going on internally gets projected externally. Anxiety has consequences, but luckily, it can also be managed. So here is my prescription for you: sit down, have a handful of almonds, or a banana smoothie, maybe add in some spinach and an avocado, and relax. Breathe deeply. You can get through this. 

Understanding the brain mechanisms associated with anxiety are challenging for researchers, never mind the non-scientist. However, some of you may be interested in going a bit deeper. Below is a more comprehensive overview of some of that ways in which neuroscience is informing us about the biology of anxiety.

WHAT EXACTLY IS GOING ON IN MY BRAIN AND HOW CAN NUTRITION HELP?
For starters, the brain mechanisms and chemicals involved in anxiety are not yet fully understood, but enough evidence exists that tells us a lot is going on within the brain. Anxiety, especially anxiety attacks, is complex, and many brain pathways (called neural circuits) and brain chemicals (called neurotransmitters) are affected. Let’s begin with the amygdala, a structure within the brain where emotions, including fear, are processed. It makes sense then that this brain region is hyperactive during a burst of anxiety (or an anxiety attack). The amygdala has reciprocal connections to the prefrontal cortex (PFC), the brain region that regulates thought and that is responsible for focus, concentration, and attention. If the amygdala is overactive, this may alter PFC functioning, which could be why we can’t seem to focus or concentrate when anxiety seizes control over us. Additionally, anxiety involves alterations in the processing of the anterior insula, the area of the brain that gives an emotional context for a specific sensory experience. It could be that an over-active response to fear in this brain area leads to a prolonged, and inappropriate, response of anxiety, or an anxiety attack. As you can probably already see, just as the brain is complex and somewhat confusing, disorders of the brain, such as anxiety, are equally as complex.

Neuroscientists and psychologists propose that a region of the brain called the pariaqueductal grey region (PAG) is also hyperactive during anxiety. This is the area involved with fear response (defense reaction). When the PAG is stimulated, studies show that it leads to an “explosive fear reaction” that resembles a panic attack; but the hyper activation of the brain does not stop here! Studies on rodents demonstrate that the anterior hypothalamic area, the medial preoptic area, and the paraventricular nuclei are hyperactive during anxiety; areas of the brain involved in a chemical stress response system called the HPA axis response that integrates stress. It must seem that the entire brain is hyperactivated during anxiety, but remember that the brain is large and complex (and somewhat of a puzzle). Although several brain regions are described to be hyperactive during an anxiety attack or during some kind of stress, some regions (believe it or not) are hypoactive—they are working a little too slow to be helpful. Some of these underactive brain regions are the cingulate cortex and the medial prefrontal cortex (mPFC). The cingulate cortex controls and manages uncomfortable emotions, such as anxiety, and is linked to the cognitive prefrontal cortex system and the emotional limbic system. If this area is underactive, then that means that whatever is making a person uncomfortable, nervous, fearful or stressed is not being managed very well. This lack of, or insuffient, ability to regulate or control stressful conditions may contribute to the sudden and severe anxious response of an anxiety attack.

THE BRAIN CHEMICALS
How about brain chemicals? Which ones are affected by anxiety? Firstly, anxiety involves an elevated level of corticoptrophin releasing factor (CRF). This brain chemical causes part of the adrenal gland to release stress hormones called gluccocorticoids. These stress hormones include cortisol and noradrenalin (aka norepindephrine). If CRF is high during anxiety, then the brain is telling the body that danger is in the environment. The result is that the body releases an excess of stress hormones and then you feel stressed-out and afraid—your heart starts pumping fast, your breathing increases, your mind is racing, and you feel kind of scared. This is the body’s normal response to fear; however, the body should also enact fear extinguishing mechanisms. This is where the brain chemical glutamate comes in, one of the brains greatest excitatory chemicals. Research has shown that glutamergic receptor antagonists (drugs that block glutamate binding sites in the brain) are effective in treating anxiety because they help facilitate fear extinction by encouraging a calmer brain. Another chemical that helps calm the brain is known by its acronym GABA. If anxiety leads to an increase in glutamate, then the ratio between glutamate (excitatory) and GABA (inhibitory or calming) is imbalanced. Treatment may involve either decreasing glutamate (through glutamate-inhibitor drugs) or by increasing GABA levels (or both). In any case, an anxious brain needs to be calmed down.

Now back to the amygdala. This brain region, as said before, processes fearful information and coordinates the threat response by integrating information from the senses, environment, and past experience. The amgydala initiates behavioural and autonomic nervous responses by sending this information through projections to motor (movement) areas and brain stem nuclei (sensory nerves). In healthy individuals, the amydgalar response is modulated or controlled by top-down processing mechanisms involving the medial (middle) prefrontal cortex region, the hippocampus, and the anterior cingulate cortex. The hippocampus is involved in memory and the anterior cingulate cortex is involved in emotional regulation and decision making. Top-down mechanisms use stored information from past experiences to help make sense of a situation or a sensation; in this case, the brain uses its past knowledge on anxiety and the given situation to help regulate the anxiety, or in other words, to tell the brain to relax and breathe. Research shows that individuals who experience frequent anxiety attacks or who have been diagnosed with one of the many types of anxiety disorders, respond to threat with increased activity in the amgydala. Research also shows that anxiety-prone people have altered insular function. As mentioned above, the anterior insula is a brain region responsible for environment-emotion evaluation. It might just be that more anxious people have more sensitive and reactive amydalas and misbehaving insulas.

Now perhaps the most important are the neurotransmitters involved in anxiety: the monoamines. More specifically, serotonin and norepinephrine are widely recognized for their roles in mood disorders like anxiety. Another brain chemical, neuropeptides, are also believed to play a role in anxiety. This group includes substance P and neuropeptide Y. Substance P increases during anxiety, prolonging the feeling and increasing the stress response, whereas neuropeptide Y modulates mood and reduces anxiety and stress, meaning that there may be a deficiency of it within the brain of those who experience anxiety attacks. Additionally, the hormones oxytocin and orexin are involved. In a rodent-model study (a study done on rats), oxytocin is shown to act on nuclei (parts of brain cells) in the amygdala, inhibiting or blocking excitatory flow from the amygdala to the autonomic nervous system (the branch of the nervous system that mediates fear response). In other words, oxytocin helps reduce anxiety by decreasing amygdalar reaction to something perceived as stressful or fearful. 

Orexin, on the other hand, may be in excess in those prone to anxiety. Orexin is the hormone involved in the “brain reward” pathway, and may lead to excess of the neurotransmitter dopamine—the brain’s greatest stimulating chemical. If dopamine increases, then the brain is on a kind of “high” where everything it perceives is heightened, including fear. This happens because the body naturally converts dopamine to norepinephrine (a major stress hormone) that then converts to adrenaline (major stimulating hormone). Research however, shows that individual differences do exist in neuroendocrine (brain hormone) sensitivity, so different people may experience anxiety because of different abnormalities in their brains. This supports the theory that anxiety attacks have a genetic basis.

This seems like an overwhelming amount of changes that go on in the anxious brain, but there is one more abnormality to explore: the chemical release system, called the HPA axis, which is responsible for the release of the stress hormones during the experience of anxiety. Here is what happens: CRF is released by a brain region called the hypothalamus, which then tells another brain region called the pituitary gland (situated just under the hypothalamus) to release adrenocorticotropin-releasing hormone (ACTH) which tells the adrenal gland to release glucocorticoids—the stress hormones. When an anxiety attack is experienced, however, and the individual is prone to anxiety (maybe because of their genetics), this system is hyperactive, meaning that it is working in overdrive, pumping out too many stress hormones and leading to heightened anxiety. What this system lacks in highly-anxious people are a strong pair of “brakes”. The negative feedback mechanism that tells the brain to work in reverse (lower anxiety and production of stress hormones) is not functioning that well. In result, anxious people have elevated CRF levels and an altered HPA axis: stress hormones are taking over! In normal, non-anxious prone individuals, gluccocorticoids should bind to receptors on the hypothalamus and pituitary gland, telling them to stop releasing any more CRF and ACTH. This is the body`s normal, natural way of lowering anxiety and bringing back a balance.

Obviously, something goes wrong in the brain during an anxiety attack. Given the diversity within the human population in terms of individual genes (called genotypes), what exactly is going wrong in the brains of those who experience anxiety may not always be the same between people. For example, perhaps one person gets anxious because they have insufficient serotonin, which may occur for multiple of reasons (i.e. not enough serotonin receptors, binding insufficiency, or low serotonin levels). But maybe another person has perfectly normal serotonin levels, but has a hyperactive HPA system or a more reactive amygdala. The reasons for an anxiety attack are many, but perhaps the most interesting is their onset. How do anxiety attacks occur? Numerous research studies done on rats have tested anxiety and fear, and most theorize that anxiety attacks arise because of the way an individual’s genes and their environment interact. 

HOW YOUR ENVIRONMENT AND YOUR GENES MAY BE MAKING YOU ANXIOUS
Pathological anxiety, or anxiety that is abnormal and interferes with everyday life, is defined as excessive anxiety that causes significant distress. An anxiety attack can be triggered in a diverse range of conditions, and involves a combination of external (environment) and internal (genetic) factors. These factors increase a person’s vulnerability to an anxiety attack and decrease the efficiency of the brain and body to reduce or prevent excessive bursts of anxiety. There are dysfunctions in neural circuitries:  inadequate “calming” mechanisms and overactive anxiety, or excitatory, mechanisms, making a person respond aversively to emotional challenges and causing prolonged and/or exaggerated stress and fear responses. A person who suffers from anxiety or anxiety attacks express inappropriate anxious behaviour, interpret a situation as threatening when it’s not (or more threatening than it is), and have a lower stress response threshold. But why does this happen?
Through rodent-model studies, scientists learned that fear and anxiety-like behaviours are polygenetically inherited, meaning that many genes contribute to anxiety. This is also true for humans, and is why some people are more vulnerable to stress response and anxiety attacks, while others seem to cope better with emotional challenges.  It may also be the case that those people with anxiety attacks have coping deficits: anxiety from the same stimulus in rodents resulted in longer lasting anxiety-related behaviour in rodents with the genotype for increased susceptibility to anxiety. 

Overall, research suggests that dysfunctions in the processing of anxiety in integrated brain circuits involved with fear, anxiety, and stress (such as the limbic, hypothalamic, and hindbrain areas) may either lead to exaggerated activation of pathways that mediate anxiety or to insufficient regulating mechanisms that suppress anxiety and stress.  The exact dysfunction can vary within individuals, and occurs because of the inheritance of an “anxiety gene” on which the environment acts upon and activates its expression. 

Remarkably, an anxiety attack is therefore more than just an unpleasant sensation: it is the product of many hyper activated brain regions and hypoactive or dysfunctional coping mechanisms, without forgetting the influence and interaction of environment and genetics. What happens in the brain depends slightly on what exactly happens in the environment: different situations evoke different brain circuitries involved in stress, emotion, and memory. Any alterations to these pathways and responses may be induced by a person’s specific genotype that makes him or her more likely to experience an anxiety attack under less aversive conditions than what would cause the average person anxiety. 


So don’t stress out too much. If you experience anxiety attacks like I do, hopefully you can find some peace of mind in knowing that it may not be you, but your genes, environment, or diet (or a combination) that is making you anxious! Inhale calmness, and exhale stress. It’s time to gain control over your anxiety by knowing about your brain.