Depression affects millions of people worldwide and is characterized by feelings of sad mood, hopelessness, irritability, fatigue and loss of interest in once pleasurable activities. Symptoms vary from person to person, but many people who are feeling down for more than several weeks, may be clinically depressed.

What are the symptoms of depression?

  1. Persistent low or sad mood
  2. Feelings of anxiety
  3. Lack of energy / fatigue
  4. Feelings of guilt, hopelessness
  5. Loss of interest in activities that were once enjoyable
  6. Irritable mood
  7. Changes in appetite
  8. Changes in sleep: either insomnia or over-sleeping
  9. Difficulty concentrating or remembering things
  10. Aches or pains, digestive problems, persistent headaches
  11. Thoughts of suicide


Depression occurs more frequently in women than in men, perhaps because of biological factors unique to women may be linked to a higher depression rate in women. Women also tend to complain of symptoms differently than men. The majority of depressed patients never seek help, although depression is highly treatable. Many depressed patients share the mistaken belief that other people will think less of them if they go to a doctor for help. Many blame the symptoms on other diseases and never seek help. Some patients have suicidal thoughts in the belief that their feelings will never change.

Depression can be caused by a combination of factors, including genetics, environmental factors, trauma and stress. Whatever the cause, the condition is associated with physiological and chemical changes in the brain, more precisely an imbalance of neurotransmitters that carry signals between nerves.

The monoamine hypothesis

Most antidepressants on the market today treat the condition by increasing the availability of monoamine neurotransmitters, nor-epinephrine and serotonin. Some antidepressants may also increase another monoamine, dopamine. Although the monoamine hypothesis has been the focus of much antidepressant research, it has also received a share of criticism.

Some antidepressant drugs work well in depressed patients despite the fact that they do not work through the monoamine pathway. Also, experiments in which monoamines were depleted in patients did not seem to cause depression in healthy people and did not make depression worse in depressed patients.


A schematic representation of a typical synapse in a “non-depressed” and “depressed” state. Synapses are tiny gaps between nerve cells. Chemical signaling molecules called neurotransmitters travel across these synapses to relay electrical impulses from a pre-synaptic neuron to a post-synaptic neuron. The monoamine hypothesis suggests that depression is the result of a chemical imbalance of the monoamines serotonin, nor-epinephrin and dopamine.

Modern antidepressant drugs work by blocking the re-uptake of monoamines from the synapse (gaps between nerve endings). This causes the monoamines to stay in the synapse longer, prolonging the signal transfer between nerve cells.

The majority of the antidepressant drugs on the market today are selective serotonin re-uptake inhibitors.

In the past, depression was often treated with tricyclic compounds or with monoamine oxidase (enzymes that break down monoamines) inhibitors.

Monoamine oxidase inhibitors are not used very often anymore, since they require the patient to follow a strict low histamine and low tyramine diet to prevent a potential hypertensive crisis.

The depression-anxiety link: Role of the HPA axis

HPA axis feedback regulation

The Hypothalamus-Pituitary-Adrenal (HPA) axis is a complex feedback system between the hypothalamus (part of the brain), the pituitary (small pea-sized gland in the middle of the brain) and the adrenal glands (on top of the kidneys).

The HPA axis is part of the neuroendrocine system that controls our reactions to stress and regulates many physiological processes, including mood and emotions, digestion, the immune system and energy usage.

Part of the hypothalamus contains nerve cells that produce and secrete two peptides, vasopressin and corticotropin-releasing hormone (CRH).

CRH and vasopressin act on the pituitary to release adrenocorticotropin hormone (ACTH), also called corticotropin.

ACTH stimulates the adrenal glands to secrete mainly cortisol (a glucocorticoid).

Cortisol is the body’s major stress hormone and has a profound effect on the body and brain. Chronic stress has been linked to an activation of the HPA axis. Monoamines such as serotonin, adrenaline and dopamine are thought to regulate the HPA axis.

Further Reading

Read more about natural depression treatment.

Disclaimer: The above information is for educational purposes only and is not intended to substitute medical advice or care. Always consult a health care professional about any health problems or illnesses that you may have.