Are you peppy yet? You ought to be, because we are going to dive back in to this paper (sent to me by Jamie some weeks ago): Beyond the serotonin hypothesis: Mitochondria, inflammation, and neurodegeneration in major depression and affective spectrum disorders.
There's all this talk about pathogenesis, chickens, and eggs. Well, I know where it ends. We chase the trail back to the beginnings (is it abuse? temperament? soda? ho-hos? winter? rancid vegetable oil? bad reality TV? the jury is still out).
But here is where it ends. Ground zero. Ratty neurons, smoking mitochondria, and brain damage. Inflammation.
Inflammation is the term for the complex biological response of tissues to harmful stimuli, such as pathogens, damages cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue.I knew there was a reason I liked this paper so much. Two sentences of real wisdom. The paper continues on to talk about cell death, mitochondria, and the cell "executioners" called capases. They are cysteine proteases that bring it when a cell needs offing. These are the cellular equivalent of the Necro-whatevers from Chronicles of Riddick. Overproduction of reactive oxygen species by shoddy, inefficiently-acting mitochondria is a central feature of neuron cell death. The tricky wicket is that mitochondrial dysfunction and cell death leads to more inflammation, dysfunction, and cell death.
The presence of an inflammatory response in major depression� is evidenced by, amongst other things, increased plasma levels of pro-inflammatory cytokines and acute phase reactants, oxidative damage to red blood cell membranes and serum phospholipids, and lowered serum zinc.Pro-inflammatory cytokines can induce depression in 70% of people treated with such agents. Elevations of cytokines have been reported in depression, anxiety, fibromyalgia, migraines, IBS, chronic fatigue syndrome, diabetes, autoimmune arthritis� of course, says any doctor. The so-called "mitochondrial cocktail" can improve mitochondrial function after a few months and includes the following: CoQ10, riboflavin, and at least one additional antioxidant (vit C, E, or alpha lipoic acid), and l-carnitine or creatine.
Older school psychopharmacologists will try the following:
Tricyclic antidepressants - they act as classical mitochondrial decouplers by hindering ATP synthesis and enhance ATPase activity. They tend to change how mitochondria function in a neuroprotective way.
SSRIs: some seem to be toxic to mitochondria at large doses, but protective at lower doses. In animal models, all antidepressants attenuate inflammation-induced brain cytokine production and prevent the development of depression induced by high dose interferon. In fact, antidepressants seem to have this effect regardless of mechanism (SSRI, tricyclic, lithium) - which is a major argument against the monoamine theory of depression.
Lithium: seems to enhance mitochondrial function in humans and rats. Long-term is even better than short-term. Lithium is the favored medicine of the gray-haired psychopharmacologist. Between the neuroprotective effects and the anti-suicide benefit, you might expect people to encourage lithium to be in the water�
Shock therapy: Yes, it is still around. Frankly, there is no faster treatment for depression and it works in refractory cases, thus is often a lifesaver. It has terrible side effects, there's no denying it. And it seems to increase the mitochondrial efficiency in rats.
Up to 50% of patients with major depression are unresponsive to medications� here is a poem from old Egyptian papyrus (from the anchor paper)
Disease has sneaked into me. I feel my limbs heavy. I no longer know my own body. Should the master physician come to me� My heart is not revived by his medicines.
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