Sunday, July 8, 2012



Serotonin is considered to be the ‘happiness neurotransmitter’, so low serotonin is thought to cause depression and the treatment for depression is to increase serotonin signalling with drugs (SSRIs like Prozac and Zoloft) .  There is some evidence to support this idea, but serotonin isn’t a happiness neurotransmitter and SSRIs take many weeks to have an effect, suggesting acute changes are not responsible, and don’t have much effect in healthy people.

People with depression have lower brain volumes, particularly in the hippocampus.  One function of serotonin is to promote neurogenesis (the growth of new neurons), which seems to be how SSRIs have a beneficial effect.  Other things that increase neurogenesis, such as exercise, zinc and long chain omega 3s are also therapeutic for depression.  But why do people with depression have lower brain volumes?

Chronic inflammation decreases neurogenesis and promotes neurodegeneration.  Depression is associated with chronic inflammation and immune suppression, which are also two characteristics of autoimmune diseases and cancer, and helps to explain the association between depression and other chronic diseases.  Pro-inflammatory cytokines can induce depression or depressive symptoms and anti-inflammatory cytokines and drugs have antidepressant effects.  SSRIs also increase an anti-inflammatory cytokine called IL-10.  Sources of inflammation such as LPS, alcohol, ROS/mitochondrial dysfunction and homocysteine can promote depression/hippocampal atrophy.

Stressful life events often precede depression.  Glucocorticoids (such as cortisol) inhibit neurogenesis and promote apoptosis, and stress triggers an inflammatory response.  Chronic stress and inflammation promote glucocorticoid resistance – a state of elevated glucocorticoids and chronic inflammation, since glucocorticoids fail to adequate suppress inflammation and HPA axis activity.  40-60% of people with depression have glucocorticoid resistance.

Further Reading:
(1) Evolutionary Psychiatry
(2) Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation

Some Strategies for Depression

This is for informational purposes only and is not meant to diagnose or treat any medical condition.

Biological Causes of Depression

For neurogenesis, ensure adequate:

  • Long chain omega 3’s (fish, grass-fed beef/lamb/dairy, pastured eggs, algal DHA (fish is generally better than fish oil))
  • Exercise*
  • Zinc (most foods, particularly animal foods and especially shellfish)
  • Sleep, while optimising circadian rhythms (sleep at night, in the dark, without much blue light or food prior to sleeping, and with light and exercise during the day.  See here)

For inflammation, reduce/manage:

* I don’t know which kind of exercise is best for neurogenesis.  Aerobic exercise is mentioned more often.  My speculation is that exercise done outdoors where you’re learning and performing more complex movement patterns is probably more effective.  However, for many people, particularly those with depression, finding an exercise program that you feel motivated to do and can stick to long term is probably be more important than doing the ‘right’ exercise for neurogenesis.

Psychological Causes of Depression

There’s often either a focus on the biological side of depression/mental illness or on the psychological side, but both are important.  (Although to simplify things, all thoughts are a result of neurons releasing neurotransmitters to other neurons.  Yes, I’m a reductionist)

Cognitive behavioural therapy (CBT) is used by psychologists, etc to treat depression and other mental illness.  CBT basically involves changing one’s thoughts about themselves, others and the world to change behaviour; and changing behaviour (completing appropriate and scaled challenges) to change one’s thinking (‘I can do this’ or ‘that wasn’t so bad after all’)

CBT is important because in mental illnesses such as depression there is often irrational thinking* (usually self-critical in depression) that underlies the thoughts/feelings and affects behaviour.  The effect on behaviour (avoidance strategies, etc) then reinforces the negative thoughts, which causes a vicious cycle.  Some of the irrational thoughts are briefly mentioned in this three part series (see part 1, 2 and 3).  A good book for CBT is Change Your Thinking.  However, books shouldn’t necessarily replace counselling of some sort they have qualities a book can’t give you such as insight into your individual needs, a person to talk to and accountability


  1. Most enlightening; thank you very much.
    The term 'neogenesis' is woefully underutilized in our field of interest.

    Would you regard very high cholesterol numbers as a possible part of an immune response in a depressed person - an indicator for inflammation ?

    1. Potentially, but you would have to rule out other factors such as low thyroid function (which can produce similar symptoms as depression) and familial hypercholesterolemia. It would be a good idea to also use traditional markers of inflammation like C-reactive protein (CRP) and the immune cell counts.

    2. No family history, no abnormal cell counts, enough offal.
      Pampering the thyroid with some iodine, zinc and selenium may just be the stone to kill those two special birds with.
      It'll be interesting to see whether serotonin levels will then play ball as well.