"Researchers in the field of psychoneuroimmunology have developed a cytokine hypothesis of depression, which argues that proinflammatory cytokines are the key factor controlling the behavioral, hormonal, and neurochemical alterations characteristic of depressive disorders, including much of the depression that occurs with cancer."He effectively squashed the serotonin hypothesis ... which I'll cover in an upcoming post. This inflammation hypothesis has a lot to recommend it, from my reading.
More from Dr. Weil's book:
"Because all of the early antidepressants had unpleasant side effects and serious potential interactions with other drugs and medications, pharmaceutical chemists continued their search for better ones with more specific action. But what specific action should it be? Some thought deficiency of norepinephrine was the biochemical cause of depression. Others argued for a serotonin hypothesis of depression and looked for compounds to prevent its breakdown or reuptake. The proponents of the serotonin hypothesis would win the day; their big discovery came in the 1970s, again, interestingly enough, as a result of work with antihistamine.He says that Thorazine and other phenothiazines marketed as tranquilizers, and tricyclic antidepressants which preceded SSRIs were also derived from work with antihistamines:
Very likely you have taken Benadryl (diphenhydramine) at some point in your life. It is one of the oldest and most widely used antihistamines, the first such drug to be approved by the FDA for prescription use. Benadryl is so sedating that it is now sold over the counter as a sleep aid. In the 1960s this tried-and-true drug was found to have an action independent of its effect on histamine; it selectively inhibited the reuptake of serotonin. By modifying this molecule, scientists at Eli Lilly and Company in the 1970s came up with the first safe and effective selective serotonin reuptake inhibitor [SSRI], fluoxetine, much better known by its brand name Prozac. The rest is history."
"Although antihistamines are best known for blocking the effects of the compound responsible for certain immune responses, they also affect the brain."So, if antihistamines affect the brain, I suppose histamines affect the brain?
Wikipedia says that one role of histamines is as neurotransmitters. And that receptors for histamine are found on cells of the central nervous system, affecting release of the mood-altering substances norepinephrine and serotonin.
And histamine may be just one of a number of inflammatory compounds that impact brain function:
"Over the past decade, a flurry of research has suggested allergic reactions cause feelings of fatigue and depression because of the release of proinflammatory cytokines, proteins released by immune cells rushing to protect an allergic person from pollen or other allergens that have entered the body, says Paul Marshall, a clinical neuropsychologist in the department of psychiatry at Hennepin County Medical Center in Minneapolis.Related: Allergies Can Increase The Risk Of Depression, New York Times, April 2011
"It's thought that those cytokines directly affect the central nervous system, causing the release of a chemical in the brain called IL-1 beta that induces sickness behavior, such as weakness, lethargy, low mood and the inability to concentrate," Marshall says."
- Seasonal Allergies Could Spark Depression, Fatigue, USAToday, March 2008
It makes me wonder just how much of the epidemic of depression is related to inflammation, and, in turn, to not only seasonal allergies but to pro-inflammatory diets. Not unlike other inflammation-related diseases ... diabetes, heart disease, arthritis.