Intended for healthcare professionals

Rapid response to:


Serotonin and depression

BMJ 2015; 350 doi: (Published 21 April 2015) Cite this as: BMJ 2015;350:h1771

Rapid Response:

Serotonin, chronic fatigue syndrome and mitochondrial dysfunction

I mentioned chronic fatigue syndrome in my previous comment on serotonin and depression to point out how intestinal serotonin deficiency (95% of body's serotonin reserve) can link depression, chronic fatigue and chronic pain syndromes and even sleep disturbance.

Sleep disturbances of depression and chronic fatigue syndrome could be linked to low intestinal serotonin production. The pineal gland produces melatonin, the major hormone of circadian rhythm from serotonin. Based on this concept, sleep disturbance is a metabolic disease.

I have noticed that over 3 decades Myalgic encephalitis/ chronic fatigue syndrome (also known as systemic exertion intolerance disorder) (ME/CFS/SEID) guidelines have been relicating the faulty model of DSM-V psychiatric diagnostic model. We cannot and should not accept a debilitating disorder based on 5 symptoms and accept them as “idiopathic” and surrender to disability. That is what DSM does to the psychiatric population- labeling them with major debilitating disorders without looking deeper in the biology of the human body as a metabolic unit. My metabolic approach is to broaden the exclusion criteria of chronic fatigue syndrome without limitation until the cause of the chronic fatigue is found.

I do believe in every single symptom of ME/CFS/SEID. They are all genuine. None of the symptoms of ME/CFS/SEID is psychosomatic or hypochondria. I have dedicated 17 years of my career to the study and practice of chronic fatigue. Only a sweeping metabolic approach can find the cause of the fatigue and the other symptoms of this syndrome. Every patient could have a different cause if subjected to an extensive metabolic evaluation. Even if there is mitochondrial dysfunction in ME/CFS/SEID, it is not mitochondrial DNA mutation. There might be some defect in mitochondrial oxidative metabolism, most likely that is not a cause but it is a result. It was actually just published 2 weeks ago in the reference I am quoting below that while the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson's disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology.

I do have a biological and metabolic explanation of every single component of ME/CFS/SEID. I was merely mentioning neurotransmitter concept. Mitochondrial oxidative metabolism is impaired not as a cause but as a result of global nutritional deficiencies, malabsorption, defects in mineral, vitamins, glucose metabolism and hormonal imbalance. The details of this metabolic approach will come out elsewhere, not here, lest we would be deviating from the topic of neurotransmitters. Based on serotonin concept, we should be looking at the gastrointestinal tract, with all its complexities (genetic, immunological, nutritional and endocrine aspects) if we want to solve the puzzle of neurotransmitters and the puzzle of ME/CFS/SEID. That is what I mean by metabolic approach to everything.


Morris G et al. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders.BMC Med. 2015 Apr 1;13:68.: 10.1186/s12916-015-0310-

Competing interests: No competing interests

04 May 2015
Shirwan Mirza, MD, FACP, FACE
Assistant professor of medicine- Upstate Medical University, New York
Upstate Medical University, New York
399 Grant Ave RD, Auburn, New York, USA