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Anxiety & GABA

Posted Kelly Engelmann, CFNP Blog

Anxiety is the body’s natural response to danger, an automatic alarm that goes off when the body feels threatened, under pressure, or facing a stressful situation.  The feeling of anxiety is not always a bad thing—in moderation anxiety can help the brain stay alert, stay focused, initiate action and motivate behavior. However, if anxiety is chronically activated, it can be overwhelming. If anxiety is interfering with daily activities or relationships, then it stops being functional and can actually be an anxiety disorder.

According to the new ICD-10 guidelines, 5 anxiety is:

  • A category of psychiatric disorders which are characterized by anxious feelings or fear often accompanied by physical symptoms associated with anxiety
  • A disorder characterized by apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable stimulus
  • Disorders characterized by anxiety or dread without apparent object or cause. Symptoms include irritability, anxious expectations, pangs of conscience, anxiety attacks, or phobias
  • General term for the group of specific, anxiety-related, avoidance- prone disorders
  • Persistent and disabling anxiety

Anxiety is the most prevalent psychiatric disorder and is an important cause of functional impairment. Anxiety most frequently precedes other comorbid psychiatric disorders such as depression and substance abuse.7

Emotional Symptoms of Anxiety

  • Feelings of apprehension or dread
  • Trouble concentrating
  • Feeling tense and jumpy
  • Anticipating the worst
  • Irritability
  • Restlessness
  • Watching for signs of danger
  • Feeling like your mind has gone blank

Physical Symptoms of Anxiety

Anxiety is more than just a feeling. As a product of the body’s fight-or-flight response, anxiety involves a wide range of physical symptoms. Common physical symptoms of anxiety include: 6

  • Pounding heart
  • Sweating
  • Stomach upset or dizziness
  • Frequent urination or diarrhea
  • Shortness of breath
  • Tremors and twitches
  • Muscle tension

GABA to the Rescue

GABA is the brain’s primary inhibitory neurotransmitter, and helps modulate the stress response by balancing excitatory neurotransmitters.

Gamma-aminobutyric acid was first synthesized in 1883, and was initially known only as a plant and microbe metabolic product. In 1950, GABA was discovered to be an integral part of the mammalian central nervous system.1

Exogenous GAGA does not cross the blood brain barrier.2 To have an inhibitory effect in the brain, GABA must be synthesized in the brain. GABA synthesis in the brain requires glutamate and the enzyme glutamate decarboxylase (GAD) and pyridoxal phosphate (B6) as a cofactor. This process converts glutamate, the principle excitatory neurotransmitter, into the principle inhibitory neurotransmitter GABA.3,4

Too much excitatory activity without adequate GABA inhibition can lead to symptoms such as restlessness, irritability, insomnia, and even seizure activity. GABA’s job is to produce relaxation, analgesia and sleep.

Glutamate elevation without GABA’s inhibitory control is dangerous to the brain, due to the excitatory nature of excessive glutamate. High glutamate can lead to neuronal cell death and neurodegeneration. Glutamate receptors also pull other excitatory substances into the cell besides glutamate, such as:

  • Aspartate (which can be converted to glutamate)
  • Aspartame
  • Aspartic Acid
  • Glutamate
  • Glutamine
  • Glutamic Acid
  • Cysteine
  • Homocysteine

Each of these can bind to the glutamate receptor which results in excessive stimulation and contributes to the imbalances of GABA and glutamate. The more glutamate receptors you have, the more excitatory substances will be pulled in.

GABA: a Balancing Act

Chronic alcohol use can lead to downregulation in the number and sensitivity of GABA receptors in the brain and can reduce GABA’s ability to bind to its receptors. Also the loss of GABA in the urine can lead to depletion of GABA stores.

Anemia may contribute to inadequate receptor binding of GABA and low GABA stores. There is primary evidence that iron deficiency in the brain can change the utilization and metabolism of GABA. The state of anemia in the body also produces a stress response which can contribute to the depletion of GABA.

Chronic stress in the body, regardless of the cause, will elevate the catecholamine neurotransmitters and, over time, can contribute to GABA depletion. The body does not discern the cause of the stressor, whether physical, chemical or emotional, and will respond the same for each stressor. The standard Western lifestyle tends to drive a sympathetic dominate state, the over-fed/under-nourished, over-scheduled, sleep-deprived and chemically-laden lifestyle can be one of the main contributors to GABA imbalance.

Deficient vitamin B6 can be caused from poor diet, protein-energy under-nutrition, alcoholism, malabsorption and excessive loss. The concentration of GABA in the brain is controlled by two P5P (pyridoxal 5′-phosphate)-dependent enzymes, glutamate decarboxlyase GAD and GABA transaminase (GAD-T). Vitamin B6 is the primary cofactor in the conversion from glutamate to GABA, so depletion from any cause can contribute to low GABA and symptoms of anxiety.

Strategies for Improving GABA Balance

  • Limit the use of alcohol. Alcohol can cause a sedative effect but chronic use will deplete GABA.
  • Manage stress! Long-term stress—physical, chemical or emotional—can impact GABA levels and cause anxiety. Developing strategies and tactics to modulate the stress response and HPA axis will be beneficial under any circumstance.
  • Assess for and treat anemia.
  • Replete B6 as the cofactor for conversion of glutamate into GABA.
  • Replete taurine. The amino acid taurine increases the enzyme GAD and consequently GABA levels. Additionally, taurine doubles as an inhibitory neurotransmitter and can bind directly to GABA receptors, so it can provide balance naturally in that manner as well. Taurine is found in seafood and animal protein.

Urinary testing for levels of GABA, glutamate and the catecholamines can provide a window into brain chemistry and guide both initial treatment and the monitoring process.

 

References

  1. Roth RJ, Cooper JR, Bloom FE, (2003) The biochemical basis of Neuropharmacology Oxford: Oxford University Press p.106
  2. Kuriyama K, size PY (Jan 1971) ” Blood brain barrier H3-y-aminobutyric acid in normal amino oxyacetic acid- treated animals”. Neuropharmacology. 10(1):103-108
  3. Pet riff OA, (December 2002). “GABA and glutamate in the human brain” Neuroscientis. 8(6): 562-573.
  4. Schousboe A, Waagepeterson HS(2007). “GABA: homeostatic and pharmacological aspects.” Prog. Brain Res. Progress in Brain Research. 160:9-19.
  5. ICD 10 Data.com
  6. Melinda Smith, M.A., Lawrence Robinson, and Jeanne Segal, Ph.D. Last updated: May 2016
  7. Martin, Patrick MD, PhD, “The epidemiology of anxiety disorders: a review. Dialogues in Clinical Neuroscience, 2003 Sept: 5(3): 281-298
Kelly Engelmann, CFNP

Kelly Engelmann, CFNP

Kelly B. Engelmann is a Family Nurse Practitioner certified by the American Nurses Credentialing Center, The Fellowship in Anti-Aging, Regenerative and Functional Medicine and the American Board of Anti-Aging HealthPractitioners.

She earned an undergraduate nursing degree from the University of Mississippi, a graduate degree from the University of Southern Mississippi, a master’s degree in Metabolic and Nutritional Medicine from the University of Southern Florida Medical School and completed the fellowship in Anti-Aging Medicine with The American Academy of Anti-Aging Medicine (A4M).

She is very active in and committed to both the Mississippi Nurses Association and the American Nurses Association.

Kelly has been providing care to the people of Mississippi since 1997. She is truly passionate about the health and wellness of her patients and their families. One of her personal goals in life is to create a sense of community in her practice for resources to inform and inspire Mississippians to live a more balanced, healthy lifestyle. Kelly is in a collaborative agreement with Dr. Zilin Wang.
Kelly Engelmann, CFNP