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Depression Brain. Folate and Anti-Oxidants can help protect against damage

Depression brain.  Depression damages the brain and contributes to memory problems

Depression is a brain disorder that interferes with many aspects of function.  The evidence for genetic susceptibility to depression is strong, although it may take a traumatic event, or even a series of traumatic events, to trigger it. The brains of people with depression differ from those of people who are not depressed.  Brain imagery studies show differences in brain regions related to cognition, sleep patterns, feeding behavior and sleep.  Studies have also demonstrated smaller brain volume, greater susceptibility to Alzheimers disease, heart disease and memory problems.  Depression is a bio-chemical problem that is strongly associated with other serious medical conditions that can further reduce quality of life and lifespan.

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How is depression related to other diseases?

There is increasing evidence that depression may increase risk of other diseases by changing body chemistry.  These alterations may lead to decreased levels of anti-oxidants and increased oxidative stress.

Depression Brain and the Chemical Stress of Depression

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Depression has been associated with elevated cortisol levels.  The general thought, originating with Hans Selye’s research, is that elevated cortisol leads to suppression of immune function.  There is a lot of good evidence supporting this, but more recent research indicates that even though cortisol levels may be elevated in depression, the immune system is not turned down– or at least not in the brain.  Increased immune activity can cause oxidative damage to surrounding tissues. One of the ways the immune system protects the body from attack is by blasting offensive material with highly reactive chemicals such as hydrogen peroxide.  The hydrogen peroxide blasts releases free oxygen, which damages the cell membranes of targets, and destroys them.  The blast is called an “Oxidative Burst.”  Another type of “Blast” is created by production of nitric oxide.  That type of “blast ” is a nitrosative burst. These “bursts” can damage healthy cells, especially when there is no appropriate target, such as infectious organisms.  New research is showing that depression increases immuno-inflammatory activity.  This activity can damage:

  • Lipids and Cell Membranes.  This can cause cell death
  • Proteins.  Also not good.
  • DNA.  DNA damage can result in cancer
  • Mitochondria.  Mitrochondria are needed to produce energy for cells.

Depression is also associated with

  • Reduced neurogenesis (growth of brain cells)
  • Reduced brain volume (popularly known as “raisin brain.”)
  • Memory problems and etc.
  • Increased vulnerability to Alzheimer’s disease

Increasing immuno-inflammatory pathways can lead to decreases in production of melatonin and serotonin.

When the body increases activity of one pathway another pathway may be left with insufficient resources.  Upping the activity of the immune system may mean lowering activity of something else.  The molecule tryptophan is used in production of interleukins and tumor-necrosis factor alpha during activation of immunol-inflammatory pathways.  Tryptophan is also used in production of the neurotransmitter, Serotonin and the hormone melatonin.  Tyrptophan levels tend to be low in depressed people.  So are levels of serotonin and melatonin.  This may be because the demand for tryptophan is increased. Low serotonin is believed to be one of the factors causing the feelings of sadness and worthlessness of depression.  Anti-depressants such as Selective Serotonin Re-uptake Inhibitors (SSRIs) help maintain levels of serotonin.  Melatonin is a hormone that helps regulate the sleep cycle.   Sleep disorders are hallmarks of depression.  It gets a lot more complicated and there is a lot more biochemistry involved.  If you want to learn more check out the references at the bottom of this article.  The point I’m hoping to make is that people who suffer depression may also be suffering more oxidative stress than is good for them and that depression is more than a psychological problem.

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A question about depression.

Are the feelings of sadness, guilt, worthless , low serotonin and etc. secondary side effects of something else?  Robert Sapolsky has likened depression to the response one would have to a crushing physical injury.  Getting munched by a sabre-toothed tiger and surviving would mean an extended period of healing.  It would be good to get your immune system up and running, because bacterial infection would be sure to set in next.  Forget the neurotransmitters for now.  You should be asleep anyway.  Maybe in depression the body is settling in for a tedious recooperation and is then unable to turn off the response.  People can stay depressed for years. And apparently it can be very difficult to help break a patient out of it.  But what about long-term oxidative or nitrosative damage being done during the time someone is depressed?  Could increasing anti-oxidants help?  Could anti-oxidants protect depressed people from neuronal degeneration, shrunken brain volume, memory impairment and inability to think straight?

Anti-Oxidants and Depression.

Anti-oxidants may help.  Maybe.  There has been some interesting work on people who have genetic variants for an enzyme (MTHRF) important in folate metabolism.  Folate is a B vitamin.  Folate metabolites, like vitamins C and E, are powerful anti-oxidants.  Some people, for genetic reasons, are unable to metabolize folate very well.  People with genes that do not allow for efficient metabolism of Folate are at higher risk of depression (and several other disorders, including migraines).  By some counts, around 70% of people with major depressive disorder are poor folate metabolizers. People who have difficulty metabolizing folate can get around the problem by taking a folate supplement that is already in an advanced form: L-methylfolate.  In fact, some doctors are prescribing L-methylfolate along with anti-depressants to their depressed patients.  Deplin is a prescription L-methylfolate.  You can also get L-methylfolate non-prescription strength from health food stores or Amazon.  It is not yet understood how L-methylfolate may relieve depression.  But it is a strong anti-oxidant.  Does it help by reducing oxidative stress?  Would other anti-oxidants be helpful in treating depression, or in reducing the damage depression inflicts on the body?  We’ll be keeping on eye on research developments.

Final Takeaway

If you are suffering from depression get treatment and try to eat well.  Even if its hard.  A little L-methylfolate might help.

Papakostas, G., Shelton, R., Zajecka, J., Etemad, B., Rickels, K., Clain, A., Baer, L., Dalton, E., Sacco, G., Schoenfeld, D., Pencina, M., Meisner, A., Bottiglieri, T., Nelson, E., Mischoulon, D., Alpert, J., Barbee, J., Zisook, S., & Fava, M. (2012).L- Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials American Journal of Psychiatry, 169 (12) DOI: 10.1176/appi.ajp.2012.11071114

Haroon E, Raison CL, & Miller AH (2012). Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37 (1), 137-62 PMID: 21918508