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Anxiety

Acids in the Brain: A Cause for Anxiety?

Studies suggest that acid-base imbalances in the brain could trigger panic.

Key points

  • Panic attacks are common. About one in five people will experience a panic attack at some point.
  • Panic attacks may be related to too much acid in the brain, recent studies suggest. Panic attack sufferers may have unbalanced acid-base levels.
  • People who suffer from panic disorder have a hypersensitive suffocation alarm in the brainstem.
  • Future treatments for panic disorder should attempt to target acid-base levels in the brain and/or acid hypersensitivity.

Anyone who has experienced intense, anxious fear knows how frightening it can feel. Panic attacks are shockingly common. The lifetime prevalence of panic attacks is 22.7 percent—that is more than one of every five people who will experience a panic attack in their lifetime (1).

A panic attack is a sudden episode of intense fear that triggers severe physical sensations even though there is no real danger. During the episode, the person is debilitated. A person may feel some of the following in addition to other idiosyncratic bodily sensations that peak within a few minutes after onset. According to the DSM-5, at least four out of the following symptoms must be met for a panic attack:

  • Pounding heart
  • Sweating
  • Trembling or shaking
  • Shortness of breath
  • A feeling of choking
  • Chest pain or discomfort
  • Nausea or stomachache
  • A feeling of dizziness, lightheadedness, or faintness
  • Depersonalization (a feeling of being detached from oneself) or derealization (a feeling of unreality); fear of losing control or going crazy
  • Fear of dying
  • Paresthesia (numbness or tingling sensations)
  • Chills or hot flushes

Many of the above symptoms mimic cardiac arrest, acute asthma, or other seeming medical emergencies, even though there is actually no real danger. Thus, the person can receive expensive medical tests without receiving a medical diagnosis.

When a panic attack is accompanied by a period of at least one month of anticipation anxiety and/or significant maladaptive changes in behaviors, the panic attack can escalate into a panic disorder. Some patients with panic disorder avoid most situations or even become confined to their homes. These attacks are often not triggered.

What Causes Panic Attacks?

Many scientists have attempted to explain the causes of these attacks. However, some recent brain studies have revealed some clues about the causes of recurrent panic attacks: it may be a problem of too much acid in the brain.

Keep in mind that an increase in acidity causes a decrease in pH level. The pH level of our brain is heavily regulated. We have acid-base sensors in the brain. A large increase or decrease in brain acidity can cause havoc in neurocircuitry function.

The change in acidity at synapses is detected by specialized proteins conveniently called “acid-sensing ion channels,” or ASICs. When these proteins sense acid, they stimulate neurons. The detected increase in acidity and disruption of acid-base homeostasis in the brain can lead to fear and panic (2).

In fact, genetically modified mice that lack the acid-sensing proteins ASIC show reduced instinctive and/or learned fear (3). It is not surprising that this protein is involved in fear, because they are found in fear-important brain structures such as the amygdala (3). In other words, the amygdala is an acid-base chemosensor and it evokes fear when it senses increases in acid.

One way to increase acid in the brain is to be exposed to air with a higher than normal concentration of carbon dioxide (CO2). Also, CO2 is an end-product of carbohydrate metabolism and is continuously produced by the bicarbonate system to maintain a physiological acid-base homeostasis. CO2 reacts with water to form carbonic acid, which in turn dissociates into hydrogen ions and bicarbonate. Bicarbonate balances by opposing the increasing hydrogen, thus restoring acid-base homeostasis.

Without a proper bicarbonate buffering system, hydrogen would decrease pH (increasing acidity in the brain). This can happen when CO2 increases rapidly. Lactate also increases acidity in the brain. In sum, all these agents may contribute to a panic attack because they increase acidity in the brain. In fact, one way to provoke panic in laboratory experiments is to administer lactate or air with high CO2 concentration.

Why Panic and Acid Hypersensitivity Go Together

Research revealed that people who suffer from panic attacks may be hypersensitive to acid in the brain, perhaps because of a genetic predisposition. This may explain why some people are more prone to having panic attacks than others.

What's more, patients with panic disorder tend to generate excessive lactic acid in their brains (3). Lactic acid or lactate is one of the products of glucose metabolism. Thus, lactate is continuously produced and consumed during brain activity. However, if lactate accumulates in the brain, the brain becomes more acidic and more prone to panic. This is more likely in panic patients (4).

Lactate is produced when the brain is active. But active brains in panic patients accumulate more lactate than in non-panic ones. For example, one study found that visual stimulation led to significantly greater visual cortex lactate in panic patients as compared to controls (4). It is unclear whether the problem is in the production or clearance of lactate in people who suffer from panic.

There are other regions in the brain that also contain pH chemosensors, such as the brainstem. These brainstem chemosensors play a crucial role in maintaining and triggering spontaneous panic attacks. Structural and functional MRI have demonstrated pathologies in brainstem regions in patients with panic disorder (5).

The brainstem has a key role in the detection of suffocation, and at a certain threshold, it will generate hyperventilation. Everyone has a suffocation alarm in the brain to ensure survival, but those who suffer from panic disorder have a more sensitive suffocation alarm. This alarm is falsely and often triggered in patients with panic disorder (6).

How This Affects Treatment

Current treatments for panic disorder consist of medications such as SSRIs, exposure therapy, cognitive behavioral therapy, and other talk therapies. New treatment approaches for panic disorder may wish to take this research into account. For example, specific breathing can balance pH in the brain and thus reduce the frequency of panic attacks. What's more, avoiding food, activities, and agents that increase acidity in the brain could decrease the likelihood of panic attacks. Thus, future efforts to treat panic disorder should incorporate ways to address the acid-base imbalance in the anxious brain.

References

(1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1958997/

(2) Leibold, N.K., van den Hove, D.L.A., Esquivel, G., et al. (2015). The Brain acid-base homeostasis and serotonin: a perspective on the use of carbon dioxide as human and rodent experimental model of panic. Progress in Neurobiology, 129: 58-78.

(3) Ziemann, A.E., Allen, J.A., Dahdaleh, N.S., et al. (2010). The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior. Cell, 139, 14 (5) 1012-1021.

(4) Maddock, R. J., Buonocore, M.H., Copeland, L.E., & Richards, A.L., 2009. Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study. Molecular Psychiatry, 14(5): 537-545.

(5) Sobanski, T., Wagner, G. (2019). Functional neuroanatomy in panic disorder: Status quo of the research. World Journal of Psychiatry, 22: 12-33.

(6) Klein, D.F. (1993). False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch. Gen. Psychiatry, 50: 306-317.

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