Anxiety

Started on September 21, 2021

Humanity has a tendency to distance itself from the rest of the animal kingdom, as if there was some bifurcation in our evolutionary paths long ago. But Homo sapiens have walked the earth for 300,000 years, compared to the 3,500,000,000 years that life has evolved on earth; that means that 99.991% of our natural selection is still shared. It seems reasonable, then, to interpret much of human behavior through an evolutionary lens. Our habits, our responses to stimuli, our behavior, is likely no different at its core from that of our evolutionary predecessors.

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Note: the psychological and physiological conclusions made here are conjecture unless a source is specifically provided.

Origins

It's important to start with a definition: anxiety is often described as a feeling of unease, sometimes about something specific and other times is simply a nebulous unease with no apparant cause. It could be the rush felt when one realizes they just locked their (using "you" from here on) keys in the car, the churning stomach you feel in the minutes leading up to an important standardized test, or the feeling that comes when you're corrected publicly by a friend after mispronouncing a new acquitances' name.

When the trigger is specific, it appears as though anxiety almost acts as a positive punishment to discourage certain behaviors. For instance, say you find yourself riding in a car with a friend who is driving 20mph over the speed limit: this experience would likely induce anxiety in most. It's almost as if the anxiety is acting as a protective measure to provide you with a negative response (a feeling of unease) in association with this stimulus (your friend driving the car) via classical conditioning. This is clearly evolutionarily advantageous: the next time your friend offers to drive, a rush of anxiety ensues, inducing you to refuse and potentially avoiding injury or death. While our brain is capable of understanding that speeding 20mph over the speed limit is more likely to induce injury and so we should avoid doing so, it seems like it may be more effective, or primal (or both) to control behavior by associating the stimulus with a visceral feeling. Intuitively, a strong cerebral understanding appears powerless against emotion. For instance: understanding the exceedingly low probability of falling through a glass floor of a tall building does nothing to assuage the anxiety of an acrophobic standing at the top of the Space Needle.

It wouldn't be unprecedented for organisms to keep around more primal systems (i.e. the gut response) to use as an auxillary/backup system when the evolutionarily newer (i.e. the brain) system isn't sufficient. For example, in the reconstitution of ATP (the simplest form of energy for cells), once phosphocreatine in muscle cells is depleted and when there is insufficient oxygen for oxidative metabolism to take place (for instance, if many muscles are being worked excessively and the circulation isn't able to provide enough oxygen fast enough), anerobic glycolysis begins to reconstitue the ATP. Anerobic glycolysis produces ATP significantly faster (about 100x) than aerobic respiration, but significantly less efficiently (only 2 ATP are produced per mole of glucose compared with 32 ATP when sufficient oxygen is present) and with the potential byproduct of lactic acid (the cause for the burning sensation in an overworked muscle)1. It's believed that anerobic glycolysis is an ancient form of energy production that organisms had before there was sufficient oxygen in the atmosphere for oxidative metabolism to have evolved2. As anaerobic respiration is to oxidative metabolism, the gut response could be an evolutionary precursor to the highly complex organ we have for guiding decision making today: the brain.

Much of the anxiety people experience is episodic and in response to specific events, but when anxiety turns pernicious is when it is sustained and with unidentified cause. We'll refer to this as primary (or essential) anxiety3. The underlying cause of primary anxiety is likely genetic (some brain chemistry predisposition), learned secondhand (by being instructed how to or observing how parents/family/friends/partners respond to stimuli), learned firsthand via trauma (PTSD, extreme conditions like starvation, a very demanding job/school, etc.), or some combination thereof.

Benefits

Those with primary anxiety occassionally are able to harness it to achieve unparalleled productivity, provided their deficiency needs are being met (water, food, shelter, health, security, as described in Maslow's hierarchy4). Primary anxiety appears able to galvanize an individual in most circumstances despite exhaustion, sleep deprevation, hunger, etc. This is understandable, as anxiety is a mental state on which survival often relies in times of hardship (being pursued by a predator, hunting for food during famine). By channeling this anxiety into certain tasks on which survival does not rely, "I'll feel better once I perfect this project", "I'll be able to relax once I finish my homework", an extrodinary reserve of work capacity is unlocked and, if left unchecked, tends toward perfectionism and completionism. Completing tasks becomes the way this "artificial" anxiety is dispelled, and since this work ethic is often rewarded by society (parental praise, financial gain), the habit of channeling anxiety as a means of productivity is reinforced. Over time, the reinforcement of this habit tends toward completionism and perfectionism, as the brain begins to anticipate that its reward will be proportional to the amount of work and quality of work completed. It's no surprise, then, that perfectionism has been found to have significant associations with primary anxiety5. The dangers of this positive feedback loop should be evident. A sustained state of this anxiety can cause ill health effects: among individuals who reported at least one suicide attempt in their lifetime, it was found that 70% had an anxiety disorder6.

Symptoms and measurement

One can think of primary anxiety as a pre-disorder form of Generalized Anxiety Disorder (GAD). That is, before the symptoms of GAD begin to interfere with daily life and it becomes a disorder. Thus, the symptoms of primary anxiety should be lighter versions of GAD's7, which are:

When in a state of primary anxiety, one acts as though they can't handle any additional hardship. This results in a fortification of control over one's resources (which often manifests as excessive frugality), environment, and life path. A common consequence of this control is inflexibility and intolerance: those with moderate primary anxiety may attempt to control or scold the actions of others in their life (especially roommates and partners) if they percieve those actions have even a slight negative impact on them. Those with severe primary anxiety may even have panic attacks when there are even small deviations from expectations.

As an attempt to settle the underlying nebulous unease, primary anxiety screams to the conscious "x needs to change for me to go away", where x is in constant flux. This results in a perpetual and incredibly uncomfortable state of unrest, during which the anxiety appears to attach itself to every aspect of one's life (e.g. "maybe re-using this disposable water bottle is causing my daily nausea", "maybe the onions I had in last night's dinner are causing my morning GERD (gastroesophageal reflux disease)", "maybe I just need to finally vaccum the entire apartment", "maybe I just need to drop off that letter at the post office", "maybe it's the unpaid credit card bill that's causing all of this stress"). The state of action (working on a task that's been stuck on your to-do list) or distraction (e.g. chopping tomatoes for your partner's dinner) are the only states where this discomfort is abated. More passive activities, such as watching TV, reading, listening to music, etc. are too regularly interrupted by the mind's eye refocusing itself on that everpresent feeling of unease and the next proposed action that could finally be the fix. By the end of each day, this guessing game and the incessant journeys that follow finally come to an end with the onset of the anxious mind's most enjoyable activity: sleep.

For those who have not experienced severe primary anxiety first-hand, it can be very difficult to imagine. A close parallel that many have experienced is when a song is stuck in one's head. This is a good example of an intrusive thought: undesired, seemingly random, and sometimes silently demanding action before it'll dissipate (singing/humming along, tapping along, etc.). Now, instead of a song or tune, imagine the intrusive thought is something like "what if I jumped onto the tracks right before the A train arrives?", or "now that I finished my leftover food at work from Monday, what am I going to eat for lunch tomorrow?", or "is my partner upset with me? Do they still love me?", or "what if I punched my best friend in the face right now?", or any of the examples in the prior paragraph that anxiety screams to the conscious. Each of these instrusive thoughts simply leads to a web of more, and your brain has to check off and explore each one, one by one, before you can take control over your consciousness again8. The issue is, the checks fade very quickly, so you have to go back and recheck each thought regularly. Unlike a song stuck in your head, with severe primary anxiety, one can expect 50 out of every 60 waking minutes to be spent tending to these thoughts.

Anecdotally, it appears as though a common theme among many of the severely anxious mind's proposed solutions is movement. Whether it's the anxiety abating after a run, or while driving between locations, or flying to California, or deciding to move back in with your parents: it appears as though the act of deciding and the subsequent movement acts as a major temporary reliever of the anxiety. It'd stand to reason that this could be a consequence of the body's "flight" response. That is, organisms that, when experiencing an anxiety response, responded with movement were more likely to survive and reproduce, and therefore we inherited this trait. Moreover, another theme is the complete opposite: an avoidance of all unnecessary movement, and the desire for isolation and energy conservation (not leaving one's apartment, not attending events with friends, wanting deliveries instead of having to go pick something up at the store). This could be a risk reducer, that is, essentially a "hiding" response, to reduce the risk of predation. Depending on the scenario, one of these responses, either running or hiding, is likely to be evolutionarily advantageous.

(Purely anecdotal) manifestations/measurements of primary anxiety are as follows:

It's remarkably natural to fall victim to the third-cause fallacy when attempting to determine the cause of primary anxiety. In particular, one may think that because an individual has decreased outgoingness and begun to display other symptoms listed above and generally fortified control over one's life, that means these are the reasons that they are anxious (and a reversal of these symptoms will resolve the primary anxiety). However, the relationship between these symptoms and the anxiety is actually spurious; they are often caused by a third, unseen variable (for instance, an emotionally abusive partner) that is inducing both the anxiety and these symptoms.

Treatment

Neuroplasticity sits at the core of treatement for primary anxiety, but it's important to recognize that, like many biological systems, changes take effort over time. Thus, while treatment is underway, it's imperative that the patient is made as comfortable as possible so that unnecessary pain is avoided (in the same way one with a broken leg rests until using it no longer causes pain) and their desires, however unreasonable, are catered to. For instance, say your partner, who is currently suffering from severe primary anxiety, prefers to drink Coke over Pepsi. If you take them out to dinner and the restauraunt only has Pepsi, you don't simply ask them if another drink is acceptable; you should suggest going to a different restauraunt (as unreasonable as that may seem). Even this unexpected event of not having Coke and having to change plans may still be very distressing to your partner, so constant reassurance is needed that they're all right and in control.

One can visualize treatment of primary anxiety (and likely depression, or any other mental state, such as addiction) with the following analogy: imagine a snow covered hill12 and a sled repeatedly sledding down this hill. As the sled goes down the hill repeatedly, one path in the snow will eventually become predominent, and so the sled will tend toward that existing, ingrained path. As the sled continues down this existing path, it becomes deeper and deeper, and thus increasingly difficult for the sled to not end up taking the path as it heads down the hill. Now imagine that the path the sled takes is a pattern of thought (like the train of thought that's started when one is asked to recall a former lover), or a habit (like brushing your teeth every morning), or a reaction when presented with a certain stimulus (like a fear of dogs that was instilled by growing up around ferals). It's difficult, and takes concerted effort, to get the sled to take a different path down the hill after one has already been ingrained, in the same way it's difficult and takes effort to break a habit or a way of thinking. The brain is really just a collection of billions of these hills, each with a sled skidding down it at a regular interval13. Given no change in outside influence on this system of sleds, as time passes, the existing paths remain the same (in fact, they likely become even more ingrained). It takes outside influence (or external "work", in the physics definition, which is applying some force over a certain distance, Work = Force x displacement) in order to cause the sled to deviate from the existing ingrained path. It's important to remember, though, that this work is necessarily external to the system of sleds. In fact, thinking (i.e. allowing the sleds to continue down their paths) without any external influence on the system, is simply ingraining the paths more and more. It follows then that within this analogy, a depressive brain, or an anxious brain, are certain configurations of these hills. Taken all together: you can't just think your way out of, or wait out, anxiety or depression; this will only result in an exacerbation of the condition. External work must be done14. For humans, this work often takes the form of exercise, talk therapy, and medication all combined with two very necessary components: the recognition that one is anxious or depressed and a desire to heal (of course, one's outlook on their mental state and their desire to heal is itself is a pattern of thought which may need changing first before therapy will be sought).

Certain experiences, like PTSD or the use of potent addictive drugs are likely to create highly ingrained paths, which means it will take significant work to create an alternative path. Conversely, other drugs, like LSD, appear to be able to undo these ingrained paths from a single use.15 In the context of the snowy hill analogy, one can think of a guided LSD experience with a psychologist as a snowfall, which makes it much easier to forge alternative, healthier paths (of course, if all of the same external stressors exist on the individual, the same paths will be created and no long term benefit had; medication and therapy must be accompanied by life changes to be indefinitely effective).

Although the effects of this external work are immediate, the core of the anxiety, depression, or addiction will remain for quite some time so long as the undesired paths are still the predominent ones. That is, even though work has been done to create an alternative path down this snowy hill, the default state (that is the resting state of the brain while no external work is being applied), is still for the sled to down the undesired path. In a sense, then, being in a state of anxiety is a binary state rather than a spectrum: can you sit in silence with your thoughts and not feel at unease?16 Once enough work has been applied, the vector will then point in the other direction, which means over time (barring no new negative environmental factors and the avoidance of triggers), the condition should tend toward improvement rather than exacerbation. This is the turning point in treatment, where relief can finally come to the mind via means other than sleep: mental calm while conscious is finally possible.

One of the worst possible situations is two cohabitants who are both struggling with primary anxiety, as it's likely that their preferences are not fully aligned and since their desires are wholly inflexible, neither is able to accomodate the other (resulting in many fights and impasses). Moreover, the stimuli that induces anxiety in one may start to induce it in the other (i.e. second hand learning), meaning an exarcerbation in both cohabitants' anxiety. The individuals should be isolated from each other and treated separately. Both individuals need treatement, otherwise the treatement of one will likely be undone over time by continuing to live with the other. Put in another way: one must remove the entirety of this mental cancer; removing half of it simply slows its inevitable spread. Anxiety, in this way, should be viewed as a mentally transmitted disease (MTD) that can transmit between any two individuals who spend a lot of time together or cohabitate. This is likely why many psychologists start by examining one's childhood, as it's probable that an untreated MTD would be transmitted from parent to child. You are the cognitive average of the company you keep.

It’s critical to recall that neuroplasticity works both ways. As easily as anxiety can be treated, it can be induced by the same factors that caused it in the first place. As mentioned above, this means that in order for treatment to stick the external factors that contributed to its development must be identified and removed, otherwise relapse is inevitable. If the cause was a friend, parent, or partner with an MTD, that person needs to be temporarily cut off and treated before being reintroduced into the patient’s life. If the cause is drug use, then clearly the use of drugs needs to be ceased while and after treatment is performed. If the cause is a stressful job or school, measures need to be taken to reduce the impact the work has on the mental state: turning off email/Slack notifications on the phone, forcing an unconditional work stoppage at 6pm, finding a new job or reducing responsibilities/class load, etc.

To the extent possible, decisions made about events/activities should be allowed to be spur-of-the-moment at the onset of said event/activity, rather than in advance. This is because the anticipation of events also appears to exacerbate the experience of anxiety (in both healthy adults and those with GAD). Studies found that prior to being asked to touch a hot stove17,18 or being shown an aversive picture19, the amygdala (a region of the brain associated with anxiety) showed anticipatory activity. In fact, in those with GAD, the amygdala was activated preceding being shown both aversive and neutral pictures. Thus, it's likely beneficial to reduce or eliminate planning events with those who are suffering from primary anxiety, as even the anticipitation of an event (whether innocuous or not) is likely to be distressing.

Self-confidence

Self-confidence and anxiety appear to be inversely proportional. That is, full self-confidence is the absense of anxiety, and severe anxiety is the absense of self-confidence. Although it's common to think of one's self-confidence in a task as a scalar value, it should really be seen as a confidence interval (a range, which is commonly used in statistics). Higher self-confidence in a task then means a tighter range within which it's believed one's true ability lies. Over-confidence then would be when one's true ability does not lie within this confidence interval (specifically, that the lower bound of the confidence interval is higher than the true value of one's ability). A proxy for measuring self-confidence in a task is how often one makes a mistake: how often you miscalculate a walking path through a congested sidewalk and have to stop short, how often you think you're going to land a skateboarding trick and then don't, how often you assume you remember a fact to be true and it turns out you misrembered. Each time a mistake is made, the self-confidence for that task is adjusted to be slightly wider since one realizes that they are less sure of where their true ability lies (e.g. walking, skateboarding, remembering)20. Conversely, self-confidence in a task is built (the range tightened) by consistently not making mistakes; that is, accurately anticipating one's capability range and acting only when the task at hand falls within this range.

One also has a general reserve of self-confidence, which is in a sense a sum21 of all of the self-confidences for each task they perform. This reserve is called upon when doing something new (joining a new soccer team, learning how to lockpick, meeting a new person in the park, etc.). Since this reserve is simply the sum, that means each time a mistake is made (or perceived to be made, by a trusted bystander claiming it was a mistake), one's reserve of generalized self-confidence also takes a hit. This reserve can be diminished significantly when someone (or a set of people) you spend a lot of time with focus primarily on the mistakes you make or the flaws you have. When this reserve is sufficiently depleted, primary anxiety can ensue. This is actually a straightforward mechanism by which an MTD is transmitted. Since the brain is just an organ that exists to make sense of the streams of input from the senses and determine a response, it follows then that a brain in a state of anxiety or depression is going to interpret the senses and respond differently than one in a neutral state. Generally, a friend, partner, or parent with an anxious or depressive brain sees the world through jade-tinted glasses and will respond in kind (e.g. pointing out your mistakes and flaws, perceived or factual). This results in the depletion of your generalized self-confidence, which may eventually lead to anxiety, concluding the transmission of the MTD.

Juxtaposed against primary anxiety where one feels as though they can't handle any additional hardship and must consciously and carefully calculate each outcome to ensure additional hardship is avoided, individuals who are self-confident feel as though they can weather most storms life throws their way (anxiety is the state of choosing "flight" / "hide", self-confidence is the state of choosing "fight"). Thus, the larger one's self-confidence, the less hesitation they act with because they feel as though they can handle any outcome. As a corollary, then, self-confidence can be equated to the ease with which one can act/speak based on an observation or piece of data. This can approach the point where certain acts are so automatic that they feel like instinct and require no conscious intervention of thought (for many of us who have reached adulthood, we have gotten to the point where walking, for instance, is autonomic). With practice, it seems any skill can reach this level of automaticity (passing a soccer ball with our left foot, playing an F sharp minor scale on piano, etc.) and with increased self-confidence, every decision becomes easier to make (what you're going to say next, what you're going to eat for dinner, what design you're going to choose for a product you're creating, when you're going to ask if you can kiss someone, etc.)

Intelligence

Intelligence plays a rather interesting role in one's experience of primary anxiety. Intelligence can be thought of as the ability to observe details, filter out extraneous information, and draw a connection between two disparate pieces of data (a good example is the ability to manufacture analogies and puns). Confidence sits orthagonally to intelligence (imagine an x-y plane, with vacantness and intelligence on the x-axis and confidence and anxiety on the y-axis), and as discussed earlier is the ease with which one can act/speak on data (the details noticed/connections made by the intelligence). It's understandable, then, why primary anxiety can be especially crippling to those who are also intelligent: when trying to make a decision, the intelligent person sees the 1,000 variables at play and has difficulty acting without incessant rumination on these variables, whereas the vacant person may only see 10 variables at play (likley much less overwhelming).

Humor is a great example of where self-confidence and intelligence combine. Seasoned comedians specifically are incredibly quick-witted, a testament to their self-confidence (they don't have to hesitate when acting on a piece of information). At their base, jokes often rely on connecting two (conventionally) disparate pieces of data; and the act of the listener discovering that connection for themselves ("getting" a joke) is what's amusing. It's no wonder, then, that being funny is a desirable characteristic in a partner: it's a testament to two important factors (intelligence and self-confidence).

TODO: Investigate the Default Mode Network, its role in anxiety, and potentially investigate SSRI's impact on DMN activity.


  1. Guyton and Hall Textbook of Medical Physiology, page 82.
  2. Anaerobic glycolysis. https://en.wikipedia.org/wiki/Anaerobic_glycolysis
  3. This terminology is derived from "primary hypertension"/"essential hypertension", which is used to describe hypertension which is "of unknown origin". Primary anxiety that begins to interfere with daily life would likely be classified as Generalized Anxiety Disorder. Guyton and Hall Textbook of Medical Physiology, page 240.
  4. According to Maslow's hierarchy, "deficiency needs" are the four bottom-most layers of the hierarchy: https://en.wikipedia.org/wiki/Maslow%27s_hierarchy_of_needs
  5. The relationships between perfectionism, pathological worry and generalised anxiety disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234287/
  6. The Relationship Between Anxiety Disorders and Suicide Attempts: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940247/
  7. Generalized anxiety disorder, the Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/generalized-anxiety-disorder/symptoms-causes/syc-20360803
  8. It's almost as if the decisions/calculations that the brain normally makes unconsciously have bubbled up into the consciousness (every small decision that normally is made unconsciously now hits the consciousness). Whereas the brain previously seamlessly integrated all of those inputs and made a decision trivially, the consciousness is now tasked with it.
  9. When taking a typing test, an interesting positive feedback loop can occur that reduces speed: a mistake is made, which induces a small amount of anxiety, which in turn distracts the brain and causes hesitation or another mistake to be made, which in turn adds to the anxiety, ad infinitum until conscious thought is able intervene and calm the nerves.
  10. It should be clear why this is evolutionary in origin.
  11. Being able to procrastinate appears to be a sign of a (presently) healthy mind. When primary anxiety has taken hold, one's priorities are often to appease the anxiety unease (by getting important things done) over enjoying the moment (procrastinating). This is likely because it feels as though the moment can't be optimally enjoyed until the unease is lifted, so it's better to wait to enjoy the moment until the unease has been dealt with. The issue is this instinct needs to be fought, not embraced, in order to lift the unease: endeavoring to improve the condition of one's future at the cost of one's present will only exacerbate the anxiety, making it even harder to recover (another positive feedback loop).
  12. The Mind, Explained: Psychedelics. https://www.netflix.com/watch/81062192
  13. In the same way a CPU advances the state of a computer to perform calculations; its clock ticking at a regular interval, advancing the flow of electricity from the hard drive, to RAM, to registers on the CPU die.
  14. Anecdotally, it appears as though those in a state of depression or anxiety benefit from hanging out with friends (even though the initial reactions to the prospect include: "it's not going to help", "I can't see anyone right now", "nobody wants to hang out with someone who is depressed/anxious like this" etc.) However, post hangout, one almost always feels a bit better (at least temporarily). This very likely could be because something outside your brain (your friends) are acting upon it: external (positive) work is being done.
  15. "Acid Test": The case for using psychedelics to treat PTSD, depression. https://www.washingtonpost.com/lifestyle/magazine/acid-test-the-case-for-using-psychedelics-to-treat-ptsd-depression/2014/09/04/03c3c222-0e01-11e4-8c9a-923ecc0c7d23_story.html
  16. This could still be a spectrum though, it could just be that it's a matter of how long you can go before you feel anxious with your thoughts. Severe anxiety would have it be 10-15 seconds during passive activities.
  17. The Mind, Explained: Mindfullness. https://www.netflix.com/watch/81062191
  18. Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787201/
  19. Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. https://pubmed.ncbi.nlm.nih.gov/19122007/
  20. An interesting aside: the illusory superiority phenomenon (also known as the above-average effect) would dictate that the worse one is at a task, the worse they are at evaluating their performance in said task. This has interesting parallels with self-confidence. Namely, the larger the range of self-confidence (the worse they are at a task), the illusory superiority phenomenon would have it that individuals will tend to believe they are in the upper half of the the range, when in fact they aren't.
  21. Technically, it's the sum of the inverse differences, something like 1/(m-n), since smaller intervals means higher self-confidence.