Inflammation, mitochondrial dysfunction and neurodegeneration in major depression

Is depression mainly a disorder of serotonin regulation? A paper just published in Progress in Neuro-Psychopharmacology and Biological Psychiatry reminds us that, of course, it is not. The authors state:

“For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression.

They observe that there is a relationship between depression a number of other conditions with a common set of underlying causes:

“…depression is one of a family of related conditions sometimes referred to as the “affective spectrum disorders”, and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others.”

What do these disorders have in common?

“…we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders.”

In the functional approach, the evaluation and treatment of depression is not complete without addressing the factors that contribute to neuroinflammation, neurodegeneration and mitochondrial dysfunction with the appropriate tests and physiological interventions.

Major depression and low Coenzyme Q10

Neuroendocrinology LettersBrain inflammation and oxidative stress are important aspects of the biological component of major depression. The authors of this interesting paper recently published in the journal Neuro Endocrinology Letters state that “There is now evidence that major depression is accompanied by an induction of inflammatory and oxidative and nitrosative stress (IO&NS) pathways and by a lowered antioxidant status. Coenzyme Q10 (CoQ10) is a strong antioxidant that has anti-inflammatory effects.” They go on to report “We found that plasma CoQ10 was significantly (p=0.0002) lower in depressed patients than in normal controls,” and note a particularly strong correlation in those with treatment resistant depression (TRD)  or chronic fatigue (CFS). They find “The results show that lower CoQ10 plays a role in the pathophysiology of depression and in particular in TRD and CFS accompanying depression.” Interestingly, they conclude with an observation that links the cholesterol lowering statin drugs to the risk of depression: “Since statins significantly lower plasma CoQ10, depressed patients and in particular those with TRD and CFS represent populations at risk to statin treatment.”