The “Chemical Imbalance” in Mental Health Problems

Norepinephrine: Arousal to Panic

Norepinephrine: From Arousal to Panic

Norepinephrine (NE) is the neurotransmitter often associated with the “fight or flight” response to stress. Strongly linked to physical responses and reactions, it can increase heart rate and blood pressure as well as create a sense of panic and overwhelming fear/dread. This neurotransmitter is similar to adrenaline and is felt to set threshold levels to stimulation and arousal. Emotionally, anxiety and depression are related to norepinephrine levels in the brain, as this neurotransmitter seems to maintain the balance between agitation and depression.

Low levels of norepinephrine are associated with a loss of alertness, poor memory, and depression. Norepinephrine appears to be the neurotransmitter of “arousal” and for that reason, lower-than-normal levels of this neurotransmitter produce below-average levels of arousal and interest, a symptom found in several psychiatric conditions including depression and ADHD. It is for this reason that medications for depression and ADHD often target both dopamine and norepinephrine in an attempt to restore both to normal level.

Mild elevations in our norepinephrine levels produce heightened arousal, something known to be produced by stimulants. This arousal is considered pleasurable and several “street drugs” such as cocaine and amphetamines work by increasing the brains level of norepinephrine. This increased sense of arousal is pleasurable, linking these substances to their potential for addiction. Research tells us that some individuals using antidepressants develop a state of “hypomania” or emotional elation and physical arousal in this same manner. For that reason, individuals using modern antidepressants are often cautioned to notify their treating physician/psychiatrist if they become “too happy”.

Moderately high levels of norepinephrine create a sense of arousal that becomes uncomfortable. Remembering that this neurotransmitter is strongly involved in creating physical reactions, moderate increases create worry, anxiety, increased startle reflex, jumpiness, fears of crowds & tight places, impaired concentration, restless sleep, and physical changes. The physical symptoms may include rapid fatigue, muscle tension/cramps, irritability, and a sense of being on"mso-spacerun: yes">  Almost all anxiety disorders involve norepinephrine elevations.

Severe and sudden increases in norepinephrine are associated with panic attacks. Perhaps the best way to visualize a panic attack is to remember the association with the “flight or fight” response. The “flight or fight” response is a chemical reaction to a dramatic and threatening situation in which the brain produces excessive amounts of norepinephrine and adrenaline – giving us extra strength, increased energy/arousal, muscle tightness (for fighting or running), and a desperate sense that we must do something immediately. This animal response was activated in early man when a bear showed up at his cave or when faced with a tiger in the woods. In modern times, imagine your reaction if while calmly watching television, someone or something started trying to knock your front door in to attack you. In the “flight or fight” reaction, your brain and body chemistry prepare you to either run from the situation or fight to the death!

A panic attack is the activation of the “flight or fight” chemical reaction without a bear at the door. It’s as though the self-protection animal response is kicking-off accidentally, when no real life-threatening situation is present. Known now as panic attacks, they can surface at the grocery, at church, or when you least expect it. As norepinephrine is a fast-acting neurotransmitter, the panic attack may last less than ten minutes (feels like hours however!) but you’ll be rattled/shaken for several hours. Panic attacks are strong physical and chemical events and include the following symptoms:

If we think about the automobile example, a panic attack is the equivalent of your dashboard warning lights coming on – your stress level is too high. Panic attacks, or surges of norepinephrine, can also occur by accident as when created by the use of certain medications. The medications for certain medical conditions can cause a panic attack or increase our level of anxiety. Medications often used for asthma, for example, can create anxiety or panic attacks.

Treating low or elevated levels of norepinephrine in the brain involve different approaches. Low levels of norepinephrine are often treated using newer antidepressants. Many new antidepressants, known as Serotonin-Norepinephrine Reuptake Inhibitors (SNRI’s) with brand names like Effexor and Serzone, treat depression by increasing levels of both serotonin and norepinephrine neurotransmitters.

Treatment for high levels of norepinephrine, as found in anxiety and panic disorders, involves decreasing neurotransmitter levels directly or using medications which increase another neurotransmitter that inhibits or decreases the action of norepinephrine. One of those inhibiting neurotransmitters is GABA, also known as Gamma-Aminobutyric Acid.

GABA: Mania and Seizures to Relaxation and Impulse Control

Gamma-Aminobutyric Acid (GABA) is a neurotransmitter that is inhibitory, that is, it decreases the ability of other neurotransmitters to work. GABA is involved in our level of excitability. Rather than encouraging communication between cells such as Dopamine, Serotonin or Norepinephrine - GABA reduces, discourages, and blocks communication. This neurotransmitter is important in brain areas involving emotion and anxiety.

When GABA is in the normal range in the brain, we are not overly aroused or anxious. At the same time, we have appropriate reactions to situations in our environment. GABA is the communication speed controller, making sure all brain communications are operating at the right speed and with the correct intensity. Too little GABA in the brain, the communication becomes out of control, overstimulated, and chemically unstable. Too much GABA and we are overly relaxed and sedated, often to the point that normal reactions are impaired.

Low levels of GABA are associated with Bipolar Disorder, Mania. With GABA levels below average, the brain is too stimulated. We begin talking rapidly, staying up for days at a time, and develop wild and grandiose ideas. In a Manic state, we are so “high” and out of control that social problems are quick to develop, often due to hypersexuality, excessive spending, reckless decisions, risk-taking behavior, and grandiose ideas. We may feel so good that we think we are a heavenly spirit, an intellectual genius, or possessing extraordinary powers. I personally had one patient who locked himself in his mobile home and spent one week rewriting the New Testament in “hillbilly”. Another, with limited education, began purchasing books on the Theory of Relativity by Albert Einstein, sensing he may be able to use the information to invent “warp drive”.

Low levels of GABA are also associated with problems of poor impulse control, including clinical conditions such as gambling, temper tantrums, and stealing. When GABA is low in the brain, impulsive behaviors are not inhibited (stopped) by logical or reasonable thinking.

Low levels of GABA are also associated with epilepsy or seizure disorders. If we imagine a seizure as a type of electrical storm, the seizure begins at one location in the brain then rushes across and through the brain like a sudden storm. Low levels of GABA make it easy for the brain to develop seizures which is why seizures are part of the withdrawal syndrome for many substances that work with GABA such as alcohol and tranquilizers (benzodiazepines – Xanax, Ativan, Librium, Valium, etc.). Substances that artificially maintain a high level of GABA, when stopped, create a dramatic drop in GABA levels, thus creating the risk for withdrawal seizures due to the chemical instability that is created.

High levels of GABA produce more control, relaxation, and even sedation. Alcohol works by increasing GABA levels, which is why all body systems are relaxed at first – then sedated to the point of slurred speech, unsteady gait, and foggy thinking. Alcohol withdrawal, or the sudden severe drop of high GABA levels, produce a low GABA level and the possibility of seizures. Withdrawal from benzodiazepines is known to follow the same pattern. Taking forty milligrams of Valium for two years, suddenly stopping all medication, will likely produce a seizure.

Medications for anxiety create relaxation and a decrease in anxiety by increasing GABA levels in the brain. Alcoholic beverages work in the same manner; the alcohol increasing GABA levels to produce mild euphoria, loss of social anxiety, and other symptoms of intoxication. Excessive intake of benzodiazepines and/or alcohol is extremely dangerous as the high GABA level actually smothers the communication between brain neurons – sometimes to the point of a total lack of communication between neurons – also known as death.

Medications for seizures, impulse control problems, and Bipolar Disorder, Mania all work by increasing the GABA levels without accompanying euphoria. Lithium and anti-seizure medications all increase GABA into the normal range, thus lowering the possibility of seizures and producing brain chemical stability. As GABA is the neurotransmitter policeman, changes in GABA can influence all neurotransmitters but especially norepinephrine.

[ Introduction ] [ Neurotransmitter Levels ]
[ Norepinephrine: Arousal to Panic ] [ Medication ]

Written by Joseph M. Carver, Ph.D.,Clinical Psychologist Please visit Dr. Carver's website for more articles.