DEPRESSION and INFLAMMATION

The role of inflammation in depression, dementia and affective disorders is becoming clear. This helps to explain the link between chronic pain, silent inflammation and depression. Upregulation of Il-6, CRP, along with the cyclooxygenase pathway tie together how aspirin, dysbiosis and poor diet can lead to profound changes in serotonin and dopamine.

The western diet has shown to be proinflammatory and upregulate CRP and IL-6. Dysbiosis or altered gut flora can lead to leaky gut and the  absorption of various toxins and polypeptide chains that enter the hepatic circulation. This can directly stimulate inflammatory cytokine production in the liver. 

The increase in reactive oxygen species creates oxidative stress which can damage mitochondrial function. Both increased oxidative stress and lowered mitochondrial function is linked to depression. This oxidative stress causes an increased demand for anti-oxidants, especially glutathione. This increases the demand for cysteine and can affect phase 2 detoxification pathways (conjugation) in the liver. Impairment in phase 2 conjugation pathways often leads to free radical damage in the liver and increases inflammatory cytokine production. Sulfur bearing amino acids like cysteine are also linked to the activation of various vitamins like the conversion of B6 into (P5P) Pyridoxal 5 phosphate. P5P is necessary for the conversion of tryptophan into serotonin. Also, low levels of cysteine impact pantothenic acid’s conversion into CoA. This conditional demand for cysteine limits the availability of taurine. Taurine affects intracellular magnesium levels which downregulates dopamine production. Low levels of cysteine also affect methylation which is being linked to depression.

A new model of the nervous system seems to be warranted. To recognize the importance of the gut and its distinct role in modifying neurotransmitters and neural signaling, let’s subdivide the nervous system into sympathetic, parasympathetic and enteric. Also, let’s get beyond this reductionism and the focus on biochemical mechanisms and embrace a biophysical communication model. The biochemical model of cell signaling is really about membrane biophysics, energy states and electrical signals that are modulated by various biochemical messengers. This helps to explain how electrical stimulation to the brain can modify serotonin and dopamine levels. The concept of neural networks also allows for a mechanism that explains the rapid shift in brain neurotransmitters from peripheral nerve stimulation or electro-acupuncture.

Getting beyond reductionism and the biochemical model allows for an understanding of the diverse mechanisms that impact the patient's mood and overall health. Based on the available data about food we may need to shift our focus from macro and micro nutrients to understand that food is a powerful signal to all of the cells in the body. Our thoughts, emotions and the food we eat all send signals to our cells. So, at some point in the inflammatory cascade, it seems that the cell does not distinguish between the death of a loved one, a car wreck or lunch at McDonalds. 

Gil Batio
Director of Medical Technology
DynaWave