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The Serotonin Irritation Syndrome (SIS)

Also see:
THE EFFECTS OF AIR QUALITY ON THE SEROTONIN IRRITATION SYNDROME
TREATMENT OF ACUTE MANIA WITH AMBIENT AIR ANIONIZATION: VARIANTS OF CLIMACTIC HEAT STRESS AND SEROTONIN SYNDROME
Estrogen, Serotonin, and Aggression
Fermentable Carbohydrates, Anxiety, Aggression
Anti Serotonin, Pro Libido
Gelatin > Whey
Thyroid peroxidase activity is inhibited by amino acids
Whey, Tryptophan, & Serotonin
Tryptophan, Fatigue, Training, and Performance
Carbohydrate Lowers Free Tryptophan
Protective Glycine
Intestinal Serotonin and Bone Loss
Hypothyroidism and Serotonin
Estrogen Increases Serotonin
Whey, Tryptophan, & Serotonin
Tryptophan, Sleep, and Depression
Intestinal Serotonin and Bone Loss
Linoleic Acid and Serotonin’s Role in Migraine
Gelatin, Glycine, and Metabolism
Serotonin and Melatonin Lower Progesterone

“The Serotonin Irritation Syndrome is defined as a significant disturbance of normal nervous system activity and/or the malfunction of various metabolic processes which is characterized by abnormally high levels of serotonin (5-Hydroxytrlptamine or 5-HT, a highly active neurochemical) in the human bloodstream.” -Charles Wallach, Ph.D

Int J Psychiatry Med. 1978-1979;9(2):199-204.
Serotonin irritation syndrome: an hypothesis.
Giannini AJ.
Two patients were seen with multisystememic complaints and anxious feelings. Their history was similar for chronic exposure to potentially ionized atmospheric environments–a waterfall and high-voltage equipment. Physical examination showed various signs sometimes associated with hyperserotonergic states. Laboratory testing showed increased levels of serum serotonin and decreased levels of its metabolite, urinary 5-hydroxyindoleacetic acid (5-HIAA). Removal of the patients from these environments or the use of a serotonin-blocker ameliorated all symptoms and reestablished normal serotonin and 5-HIAA levels. A literature-review disclosed a similar symptom-complex reported with air-ionization during the sweep of hot winds across desert lands. Animal studies are cited in which cation aerosols are used to block serotonin metabolism, producing clinical and laboratory results some of which are similar to those seen in the patients described. It is suggested that a “serotonin irritation syndrome” might be related to cation-induced serotonin metabolic dysfunctions.

J Clin Psychiatry. 1986 Jan;47(1):22-5.
The serotonin irritation syndrome–a new clinical entity?
Giannini AJ, Malone DA, Piotrowski TA.
The literature on the possible existence of a “serotonin irritation syndrome” is examined. This syndrome is an anxiety state occurring in the presence of elevated levels of atmospheric or ambient cations and is associated with elevated central and peripheral serotonin levels. Investigation of these cations’ effects on microbes, insects, and mammals, including humans, shows a disruption of normal activity. It is suggested that clinicians become acquainted with the potential relationship between cation exposure and serotonin in their treatment of anxious patients. Further research exploring the etiology and diagnostic definition of this entity is urged.

J Clin Psychiatry. 1983 Jul;44(7):262-4.
Anxiety states: relationship to atmospheric cations and serotonin.
Giannini AJ, Castellani S, Dvoredsky AE.
Five cases are described that offer evidence for the existence of the “serotonin irritation syndrome,” an anxiety state associated with high cation environments, elevated serum serotonin, and decreased urinary 5-hydroxyindoleacetic acid. The therapeutic response and reduction in serum serotonin after treatment with methysergide and/or removal from the high-cation environment support a serotonergic basis of the anxiety.

Int J Psychiatry Med. 1986-1987;16(3):243-8.
Anxiogenic effects of generated ambient cations–a preliminary study.
Giannini AJ, Jones BT, Loiselle RH, Price WA.
The existence of the putative “serotonin irritation syndrome” (SIS) was tested in a human population. Volunteers were exposed to a highly cationized environment for two hours. Symptoms of anxiety and excitement significantly increased. During the time of exposure serum serotonin levels also increased significantly. These results support the existence of SIS as a clinical entity.

J Clin Psychiatry. 1986 Mar;47(3):141-3.
Reversibility of serotonin irritation syndrome with atmospheric anions.
Giannini AJ, Jones BT, Loiselle RH.
Clinical reports and animal studies support the existence of a “serotonin irritation syndrome.” This is a putative anxiety state caused by a rise in atmospheric cations and reversed by a corresponding rise in anions. Volunteers were exposed to generated ambient cations and anions under controlled conditions. Cations were found to increase anxiety, excitement, and suspicion. Anions reversed the effects of cations and, in addition, reduced suspicion and excitement to levels below those occurring before cationization. Implications of these findings and the possible mediation of effects by serotonin are discussed.

J Gen Physiol. 1960 Nov;44:269-76.
The biological mechanisms of air ion action. II. Negative air ion effects on the concentration and metabolism of 5-hydroxytryptamine in the mammalian respiratory tract.
KRUEGER AP, SMITH RF.
Negative air ions are shown to decrease 5-hydroxytryptamine concentrations in extirpated strips of rabbit trachea and in the respiratory tracts of living mice. An initial exposure of guinea pigs to (-) air ions causes a transient rise in urinary 5-hydroxyindoleacetic acid excretion which is not observed upon subsequent exposures. These findings are compatible with the hypothesis advanced earlier that (-) air ion effects depend on the ability of (-) ions to accelerate enzymatic oxidation of 5-hydroxytryptamine.

J Gen Physiol. 1960 Jan;43:533-40.
The biological mechanisms of air ion action. I. 5-Hydroxytryptamine as the endogenous mediator of positive air ion effects on the mammalian trachea.
KRUEGER AP, SMITH RF.
Intravenous administration of 5-hydroxytryptamine to rabbits and guinea pigs is shown to bring about changes very similar to those produced by (+) air ions, including (1) decreased ciliary rate, (2) contraction of the posterior tracheal wall, (3) exaggerated response of the tracheal mucosa to trauma, (4) marked vasoconstriction in the tracheal wall, and (5) increased respiratory rate. These effects are reversed by (-) air ions. Iproniazid, which raises 5-hydroxytryptamine levels in the animal by blocking monamine oxidase, produces similar but non-reversible effects. Reserpine, which depletes 5-hydroxytryptamine in the animal, causes changes that resemble those produced by (-) air ions, including (1) increased ciliary rate, (2) relaxed posterior sulcus, (3) hyperemia of the tracheal mucosa, (4) lowered respiratory rate, and (5) increased volume and rate of mucus flow. On the basis of these facts, the hypothesis is advanced that (+) air ion effects are mediated by the release of free 5-hydroxytryptamine, while (-) air ion effects depend on the ability of (-) ions to accelerate the enzymatic oxidation of 5-hydroxytryptamine.

Int J Biometeorol. 1978 Mar;22(1):53-8.
Absence of harmful effects of protracted negative air ionisation.
Sulman FG, Levy D, Lunkan L, Pfeifer Y, Tal E.
The absence of harmful effects of protracted negative air ionisation was studied in 5 weather-sensitive women and 5 normal men chosen at random. Negative ions were generated by the Modulion of Amcor-Amron (Herzliya, Israel). The patients were exposed separately during 8 sleeping hours and 8 working hours to the apparatus at 1–2 m distance in a 4 × 4 m room, for 2 months. Thus they were exposed to a daily uptake of 1 × 104 negative ions/cm3 for 16 h/day during 2 months. Urinary 17-KS, 17-OH, adrenaline and noradrenaline excretion was not affected by the negative ionisation. However serotonin, 5-HIAA, histamine and thyroxine excretion — if increased before — diminished by 50% on an average. There were no changes in body weight, blood pressure, pulse, respiratory rate, oral morning temperature, dynamometer grip strength, routine liver function tests, urinary pH, albumen, glucose, ketones, bilirubin, or occult blood, red and white blood count and ECG records. The EEG revealed the typical changes due to negative air ionisation: stabilising of frequency, increased amplitudes, spreading of brainwaves from the perceptive occipital area to the conceptive frontal area and synchronisation of both hemisphere tracings.

Int J Biometeorol. 1973 Sep;17(3):267-75.
Effect of negative air ions upon emotionality and brain serotonin levels in isolated rats.
Gilbert GO.
The effect of small negative air ions on the emotional behavior and brain serotonin content of isolated rats was studied. The results indicate that isolated subjects were more reactive to handling and had larger levels of serotonin than did isolated subjects undergoing continuous ion treatment. Group housed subjects were less reactive to handling than were either isolated subjects or isolated subjects intermittently exposed to ions. Thus ions were effective in reducing both emotionality and serotonin. Only continuous ion treatment was effective.

International Journal of Biometeorology, Volume 7, Issue 1, pp.3-16
The biological mechanism of air ion action: The effect of CO2+ in inhaled air on the blood level of 5-hydroxytryptamine in mice (1963)
Krueger, Albert P.; Andriese, Paul C.; Kotaka, Sadao
Abstract Mice inhaling positively ionized air exhibited a significant rise in the blood level of 5-hydroxytryptamine [5-HT]BL. This effect was duplicated by non-ionized air to which CO2 + was added but did not occur when the same amount of either nonionized CO2 or CO2 − replaced CO2 +. The rise in [5-HT]BL was associated with physiological changes that parallel those appearing after the injection of 5-HT or after administration of iproniazid. Some of the animals exposed to CO2 + in air became ill and suffered tissue damage attributable to excessive concentrations of 5-HT. A few of the mice died and at autopsy pulmonary and enteric lesions were found which also were reasonably ascribed to the increased 5-HTBL.The physiological,pathological and biochemical changes described furnish additional support for the 5-HT hypothesis of air ion action presented in earlier publications. There is good reason to believe that some of the known biological effects of gaseous ions involve other mechanisms.

International Journal of Biometeorology July 1966, Volume 10, Issue 1, pp 17-28
The effects of inhaling non-ionized or positively ionized air containing 2–4% CO2 on the blood levels of 5-hydroxytryptamine in mice
A. P. Krueger, P. C. Andriese, S. Kotaka
An animal chamber was constructed which made possible the exposure of small animals for long periods of time to uniform controlled atmospheres containing a given number of cluster ions. Monitoring of the microenvironment was made possible by the fabrication of a minaturized ion collector. Using these two developments mice were exposed to non-ionized or to positively ionized air containing either 2% or 4% CO2. Non-ionized 2% or 4% CO2 produced a fall in the blood level of 5-HT.Positively ionized 2% or 4% CO2 elicited a rise in 5-HT providing the ionic density was sufficiently great.

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