Catecholamines: Direct influence in mood and health

Catechol-awhat? Most have probably only heard the word ‘catecholamines’ in passing or during a brief lesson in science class years ago. While the name sounds confusing, catecholamines are integral to the functioning of the human body. These hormones and neurotransmitters influence stress responses, mood, and general health.

Catecholamines
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What Are Catecholamines?

Catecholamines are substances that function as both hormones and neurotransmitters depending on the location they are produced. When produced by the adrenal glands, which are two small glands positioned above the kidneys, they function as circulating hormones. However, catecholamines also act as neurotransmitters if synthesized in the nervous system or as they are sent to the brain from the adrenal glands.

Catecholamines: Fight-or-Flight Response

The fight or flight response is a physiological reaction in response to stress such as a threat, attack, and other dangers. This is how our ancient ancestors either avoided or confronted danger. While our sense of danger may have evolved over the years, the fight-or-flight response is still an important component of our protection. It is driven by catecholamines.

This response prepares the body to fight or flee (“fight”) after experiencing physical or emotional stress. First, the adrenal glands release a hormone called cortisol into the blood, which further stimulates the production and release of catecholamines like adrenaline. Heart rate increases, breathing quickens, perspiration is in excess, and blood flow is redirected from functions that are non-vital in the moment like digestion to the major organs such as the heart, brain, and kidneys.

Primary Catecholamines

Catecholamines are any naturally occurring substances function as hormones and neurotransmitters within the body. Thus, there are many catecholamines. The most common primary catecholamines consist of dopamine, epinephrine, and norepinephrine. Each is synthesized by the essential amino acid, tyrosine, and are broken down into vanillylmandelic acid (VMA), metanephrine, and normetanephrine before being excreted through urination. All of the primary catecholamines have a unique role in bodily functioning.

Dopamine

Dopamine is made in the midbrain (substantia nigrae and ventral tegmental areas) from tyrosine. It is the precursor by which the other catecholamines, norepinephrine and epinephrine, are formed. Along with its influence in the fight-or-flight response, dopamine as a neurotransmitter is associated with motivation and reward behavior, executive functions, and is critical for controlling movement.  

Norepinephrine

Norepinephrine is synthesized by dopamine. It is primarily released by noradrenergic neurons and stored in the sympathetic nervous system where it acts as a neurotransmitter. Norepinephrine is the key catecholamine for arousal. Its job is to send messages to the sympathetic nervous system, which prepares the brain to respond to the environment like in the fight-or-flight response in instances of danger.

It is important to regulate cognitive functioning like focus, attention, mood, and memory. Physically, it is essential for remaining awake and alert and has even been linked to immune function. A lack of norepinephrine leads to depression, anxiety, insomnia, fatigue, and a reduced attention span.

Epinephrine

Most recognize epinephrine as a medication used to treat severe allergic reactions. As a catecholamine, epinephrine stems directly from the adrenal glands where is stored in larger amounts than its precursor, norepinephrine. An enzyme called phenylethanolamine N-methyltransferase converts norepinephrine to epinephrine.

Epinephrine is pivotal to increase cardiac output and to regulate blood glucose levels because it increases blood flow to the liver, heart, and muscles. A deficiency of epinephrine can cause dizziness, anxiety, hyperactivity, fatigue because it is involved in metabolism, heart rate, appetite, sleep, learning, and respiratory function.

Catecholamines and Mood

Because they are neurotransmitters, they have a profound impact on mood. The reason is rather simple. To avert danger, the release of catecholamines, particularly dopamine and noradrenaline, increases anxiety. Mood changes are a precursor to communicate something is wrong (i.e. a threat) and actions must be taken to ensure safety.

These psychological effects are complexly normal—even expected—but prolonged exposure to catecholamines can be detrimental. For example, researchers at the National Institute of Mental Health (2004) have established a link between genes involved in depression as well as genes responsible for catecholamine production and metabolism. Decreased precursors of catecholamines are linked to low mood and the potential for psychomotor retardation.

Depression is not the sole mood disorder relevant to them. The symptoms of schizophrenia align with alterations in catecholamine levels. Schizophrenics experience a constant state of hyperstimulation of the neuronal systems in the location of the brain catecholamines are synthesized. Medications geared to treat the disorder are intended to lower the amount of noradrenaline contributing to the overactivity (Hornykiewicz, 1982). Additionally, manic episodes as seen in bipolar disorder are associated with the release of extreme amounts of norepinephrine.

How Catecholamines Influence Cognition

All three of the primary catecholamines are involved in the higher-order thinking processes referred to as executive functioning. The goal of the executive function is to accomplish goal-directed behaviors. Without them, we would not be able to apply appropriate decision-making. Attention, working memory, and cognitive flexibility are the executive functions most dependent on catecholamine release. Dopamine and norepinephrine are especially implicated. They happen to stimulate the prefrontal cortex of the brain, which is the location that controls these executive functions:

  • Attention—the cognitive process of focusing awareness on selected information and ignoring irrelevant stimuli
  • Working memory—storing and manipulating information
  • Cognitive flexibility—the ability to simultaneously think about multiple concepts or switch between concepts

The role catecholamines play in attention is supported by studies on subjects diagnosed with attention deficit hyperactivity disorder and Parkinson’s disease. The patients display attention deficits while possessing low amounts of dopamine or exhibiting abnormal dopaminergic activity (Clark et al., 1987). Other executive functions also rely on the same areas of the brain.

Catecholamines In Exercise

Exercise, although good for the body, induces physical stress that consequently triggers the release of catecholamines from the adrenal glands. The catecholamines, epinephrine, norepinephrine, and dopamine are necessary to power muscle activity needed for exercise because they increase metabolic activity.

Catecholamines
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When exercising, catecholamines also:

  • Improve blood flow to the muscles through vasodilation
  • Increase blood pressure
  • Increase the rate of muscle contraction
  • Make more energy available
  • Contribute to the release of hormones

Catecholamines and Cardiovascular Wellness

Catecholamines have a direct effect on the cardiovascular system via beta 1 and beta 2 receptors—the main adrenergic receptors in cardiac tissues responsible for communicating signals to the nervous system. Catecholamines are released in periods of high stress and cardiac pathologies are considered potential stressors. An increase in catecholamines speed the progression of heart failure, as well as worsening the damage of myocardial ischemia. As the heart stores catecholamines, blood pressure rises and the heart rate can become too high.

Catecholamines and Neurodegenerative Disorders

Neurodegenerative disorders are conditions that result in the degeneration of neurons (i.e. nerve cells) in the brain. Parkinson’s disease is the main neurodegenerative disorder effected by catecholamines. In Parkinson’s, damage to the neurons causes a sharp decline in dopamine levels, which impacts movement and generates symptoms like tremors, muscular rigidity, postural instability, and bradykinesia. Studies suggest the neurons containing catecholamines are fragile in these patients (Sawada et al., 2013). With dopamine as a catecholamine, destruction of the neurons supports that catecholamines contribute to the disease manifestations of neurodegenerative disorders simply due to the neurodegeneration of catecholaminergic and dopaminergic neurons.

Testing the Body’s Catecholamine Levels

Certain symptoms such as a high heart rate, difficulty sleeping, tremors, excessive sweating, elevated blood pressure, and headaches could be indicative of an imbalance in catecholamine levels. A medical professional can test levels of dopamine, epinephrine, norepinephrine, and their metabolites metanephrine and normetanephrine through urine or blood.

Catecholamine levels vary throughout the day. A urine catecholamine test is optimal, as it measures the number of catecholamines over a 24-hour time period to measure these fluctuations. The urine test entails peeing into a container provided by a doctor and then storing the container in a cool, dry place in the refrigerator. Testing catecholamines in the blood requires a blood draw. Unlike the 24-hour urine test, the blood test only measures the levels in that exact moment instead of the entire day.

What Do Elevated Catecholamine Levels Mean

Symptoms including headaches, high blood pressure, loss of consciousness, anxiety, nausea and vomiting, and excessive sweating are signs of elevated catecholamines. Elevated levels may indicate the presence of rare tumors—the most common being pheochromocytoma. Pheochromocytoma tumors develop inside of the adrenal gland. Although not malignant, they can be fatal without treatment to surgically remove the tumor. Other rare tumors characterized by elevated catecholamine levels are paraganglioma tumors that grow outside of the adrenal gland and cancerous neuroblastoma tumors that originate in the nerve cells of the brain.

Low Catecholamine Levels

While low levels of catecholamines are not typically as sinister as elevated levels, they still have the potential to cause uncomfortable symptoms. Symptoms associated with low catecholamines are:

  • Fatigue
  • Depression
  • Dizziness
  • Insomnia
  • Adrenal insufficiency
  • Anxiety
  • Brain fog  

It is always wise to consult a medical professional about any new symptoms.

References

Clark, C.R., Geffen, G.M., Geffen, L.B. (1987). Catecholamines and attention. I: Animal and clinical studies. Neurosci Biobehav Rev., 11:341–352. doi: 10.1016/S0149-7634(87)80006

Hornykiewicz, O. (1982). Brain catecholamines in schizophrenia—a good case for noradrenaline. Nature, 299(5883), 484–486. https://doi.org/10.1038/299484a0

Sawada, H., Oeda, T., & Yamamoto, K. (2013). Catecholamines and Neurodegeneration in Parkinson’s Disease-From Diagnostic Marker to Aggregations of α-Synuclein. Diagnostics (Basel, Switzerland)3(2), 210–221. doi:10.3390/diagnostics3020210