Major depressive disorder is thought to be caused by a complex interplay of genetic, biological, environmental, and psychological factors. While the exact cause remains unclear, several contributing factors have been identified
- Imbalances in neurotransmitters like serotonin, norepinephrine, and dopamine are implicated in depression.
- Family history of depression increases the risk, suggesting a genetic component.
- Traumatic experiences, loss, and chronic stress can trigger or worsen depression.
- Lack of social support and isolation can contribute to depression.
- Certain personality traits, such as low self-esteem and pessimism, may increase vulnerability.
- Chronic illnesses and certain medications can also lead to or exacerbate depression.
- The stress-induced hyperactivity of the HPA axis can disrupt neuroregulatory systems and contribute to depression.
🔁 What is the HPA Axis?
The HPA axis is a chain of interactions between:
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Hypothalamus (in the brain)
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Pituitary gland (also in the brain)
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Adrenal glands (on top of your kidneys)
What Triggers HPA Axis Hyperactivity?
When you perceive a threat (like fear, trauma, lack of sleep, or chronic stress), your brain activates the HPA axis.
Here’s how:
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Stress is detected → The hypothalamus releases CRH (Corticotropin-Releasing Hormone).
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CRH travels to the pituitary gland → The pituitary releases ACTH (Adrenocorticotropic Hormone).
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ACTH stimulates the adrenal glands → They release cortisol, the main stress hormone.
1Why Hyperactivity Happens
When stress is acute (short-term), this response is helpful—it gives energy and focus.
But with chronic stress (ongoing problems, trauma, anxiety), this system stays switched on too long.
That leads to hyperactivity of the HPA axis, meaning:
Constant release of cortisol
Disrupted feedback loop (normally, cortisol tells the brain to calm down the system, but with chronic stress, this feedback gets weaker)
Increased CRH and ACTH → further stimulation of cortisol
🔬 Effects of HPA Axis Hyperactivity
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Brain: Damage to the hippocampus (memory center), mood disorders (depression, anxiety)
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Body: Weakened immune system, high blood pressure, weight gain, sleep problems
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Behavior: Irritability, fatigue, poor concentration, emotional outbursts
When you're stressed too often, your brain keeps telling your body to release more and more cortisol.
Over time, this system becomes overactive and starts harming your body and brain instead of helping you.
That’s what we call HPA axis hyperactivity—it’s your body being stuck in "stress mode."
