How Can the Norepinephrine System Become Dysregulated in Depression?

Norepinephrine helps the brain regulate energy, alertness, attention, concentration and the response to stress.

In depression, norepinephrine is not simply “too low.” It may be too low in some brain areas and too active in others.

In the Prefrontal Cortex

The prefrontal cortex helps with:

• Concentration
• Mental energy
• Planning
• Staying alert
• Getting through tasks If norepinephrine signaling is too weak in this area, a person may experience:

fatigue, poor concentration, mental slowing and low energy.

In the Amygdala and Stress System

The amygdala helps the brain detect danger and respond to stress.

If norepinephrine activity is too strong in these stress-related areas, a person may experience:

anxiety, hypervigilance, irritability, feeling on edge and difficulty relaxing.

This means someone can feel tired and mentally drained while at the same time anxious and overstimulated.

Why Does Norepinephrine Become Dysregulated?

There is usually no single cause.

Factors such as, chronic stress, genetics, poor sleep, inflammation and changes in other brain chemicals can affect the norepinephrine system.

For example:

1. Long-term stress
2. The brain's stress system stays activated
3. Norepinephrine signaling may become poorly regulated
4. Too much activity in stress circuits

and/or

1. too little activity in attention and energy circuits
2. Depressive and anxiety symptoms may develop or worsen

A Simple Way to Think About It

Norepinephrine helps control both energy and the stress response.

When it is not properly regulated, a person may experience:

• Low energy

• Poor concentration

• Mental fatigue

• Difficulty staying alert or, in other brain areas:

• Anxiety

• Hypervigilance

• Restlessness

• Feeling constantly on edge That is why it is more accurate to describe depression as involving norepinephrine dysregulation in different brain regions, rather than simply having “low norepinephrine.”