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Serotonin and depression

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

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Neurotransmitters: the link between depression, chronic fatigue and chronic pain syndromes

In his editorial, serotonin and depression, Dr. David Healy argues that serotonin reuptake inhibitors are not as effective as tricyclic antidepressants in the treatment of depression especially the melancholic type of depression. He also argues that serotonin reuptake inhibitors have not been proven to increase or decrease serotonin levels.
Psychiatry is the only field of medicine that relies solely on descriptive diagnosis by grouping symptoms together to frame a diagnosis as described in their chaotic manual: DSM (diagnostic and statistical manual), now in its fifth edition.
Only melancholia has a distinctive biological marker, namely activation of the hypothalamic-pituitary adrenal axis (high cortisol). This high cortisol has been implicated in hippocampus neuronal cell loss in melancholic depression
The brain is the most elusive organ of the body. Doctors often simplify explanation of mental illnesses to their patients by telling them: “you do have a chemical imbalance” in your brain.
Several neurotransmitters such as serotonin, norepinephrine, and dopamine have been studied and pharmacological agents have been designed to modulate these neurotransmitters.
In my opinion, the problem with psychiatry lies in the fact that we do not have biological markers for any of the major psychiatric diagnoses.
Take for example, “brain fog”, memory loss, chronic fatigue, and orthostatic intolerance that are the hallmark symptoms of myalgic encephalitis/ chronic fatigue syndrome. yet, we lack any biological explanation of these symptoms according to the psychitaric model of symptom grouping. However, hll these symptoms could be explained metabolically.
It is true that we do not know the level of serotonin in the brain in patients with major depression- but we do know that the levels of these neurotransmitters (serotonin, norepinephrine and dopamine) matter. Serotonin modulates all aspects of human behavior: mood, memory, attention, focus, sexuality, anger and aggression. Yet 95% of all serotonin is produced in the gastrointestinal tract. Not even 1 in a million neuron in the brain is capable of producing serotonin. Most of the 15 serotonin receptors are found inside and outside the central nervous system. Serotonin regulates food intake, appetite, gastrointestinal, endocrine, pulmonary, cardiac, urogenital systems and vascular biology.
Serotonin has a major role in modulating pain perception. Serotonergic drugs are used in the treatment of migraine headaches and combined serotonin-norepinephrine reuptake inhibitors have been used in chronic pain management (such as fibromyalgia).
In my view, a metabolic approach to mental illnesses is a prudent way.
If 95% of serotonin is produced in the endocrine cells of the gastrointestinal tract, and the nutritional building blocks of all neurotransmitters (amino acids) are all absorbed in the intestine. This makes the gastrointestinal tract the primary organ to be looked at as a source and as a site of malabsorption of the nutritional ingredients of neurotransmitters (tryptophan and tyrosin).
No wonder most patients with mental disorders have gastrointestinal symptoms, the so called irritable bowel syndrome (but what irritated the bowel?). Most patients with fibromyalgia, chronic headache, and most patients with myalgic encephalitis/ chronic fatigue syndrome/ systemic exertion intolerance syndrome (ME/CFS/SEID) have symptoms that overlap with depression. Most such patients do have gastrointestinal symptoms, chronic systemic pains and subtle nutritional deficiencies such as vitamin B12 deficiency.
It is time that psychiatrists stop relying on an archaic manual and start searching for biological markers of mental disorders. A good place to start at, in my opinion, is the gastrointestinal tract, where 95% of serotonin originates, and all the nutritional building blocks of all neurotransmitters are absorbed.

1. Berger M, et al. The expanded biology of serotonin. Annu. Rev. Med 2009: 60: 355-66
2. Mirza S.2015: Constitution of good health:

Competing interests: No competing interests

04 May 2015
Shirwan Mirza
Upstate Medical University/ Syracuse, NY, USA
399 Grant Ave Rd, Auburn, New York, USA