Hydrocortisone may cause depression by lowering serotonin | Second Opinion Physician

Hydrocortisone may cause depression by lowering serotonin

Cortisol or hydrocortisone is often prescribed for inflammation, autoimmunity and arthritic conditions.  Potential side effects of steroid treatments may alter mood and behavior in the following manner:

  1. Cortisol raises copper which causes dopamine to decrease and norepinephrine to increase- this worsens depression and adds to it a level of anxiety. If you are suffering from depression and anxiety and taking hydrocortisone it would be helpful to test your copper levels and total metal burden.
  2. Cortisol lowers serotonin and dopamine which also makes depression worse, along with accompanying other low serotonin mood disorders. To know if you already have a low serotonin and dopamine associated with your condition, consider testing histamine and homocysteine for determining methylation status and urinary pyrroles to see if you have a deficiency in B6 and zinc which are precursors to the formation of these very important neurotransmitters. 
  3. Cortisol will mess up your GI track! It disrupts the protective intestinal mucosal lining and leads to microbe imbalance (increases yeast and lowers healthy probiotics). This leads to a vicious cycle of more need for anti-inflammatory help (to manage auto-antibody symptoms). Suggest getting off of cortisol by any means necessary and ask your doctor about LDN – low dose naltrexone for a better management of inflammation and pain syndromes.

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Cortisol may directly impact the brain

  • The hippocampus (memory center) contains many cortisol receptors. Excess cortisol overwhelms the hippocampus and actually causes it to decay (R).
  • Cortisol/Glucocorticoids impair declarative memory retrieval and working memory (WM) performance (R).
  • Cortisol stimulates liver detoxification by inducing tryptophan oxygenase, which also has the effect of reducing serotonin levels in the brain (R).
  • Cortisol also induces glutamine synthase, which reduces glutamate levels in the brain (not good if it’s too low or too high) (R).
  • Studies of the elderly show that those with elevated cortisol levels display significant memory loss. The damage is usually reversible (R).
  • Stress also decreases neurogenesis, or the ability to create new neurons, in our memory centers (hippocampus) (R).


Cortisol stimulates many copper enzymes, probably to increase copper availability for immune purposes (chronically elevated copper isn’t good) (R).

If you have high cortisol, you will do worse with a high salt diet and you will be potassium deficient in the long term (few people as it is get the RDA). But taking potassium supplements is not simple, because the deficiency is in your cells, not your blood.  Also, potassium raises cortisol, which isn’t good if you already have high levels. Cortisol is anti-inflammatory, but it can also cause arthritis by inhibiting collagen formation and also by lowering cell potassium. Cell potassium is always low in rheumatoid arthritis (R). The answer is to reduce stress.

Other possible effects are mental illness or a decrease in mental function (memory or learning), increased cholesterol levels, and lower life expectancy (R).

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