Background of the hypothesis

Asylum seekers and immigrants in Scandinavia are admitted to mental hospitals for psychotic disorders up to ten times more frequently than native Scandinavians [1], [2] and [3]. The high frequency of psychosis among immigrants is usually explained as a result of traumatic experiences in their countries of origin, problems with adapting to a new culture, and the fact that immigrants are often socially underprivileged [4] and [5].

The frequency of psychotic disorders seems to be particularly high among immigrants from East Africa [4] and [6], and in this group of immigrants it seems particularly common to explain psychotic behaviour as a result of cultural collision and problems with social adaptation [4] and [5]. However, some studies [6], but not all [4], indicate that the high frequency of mental disorders is not seen in second generation immigrants, who often have the same social standing as their parents. Hence, although social factors are likely to be of importance, there may also be other causes. In this article, we put forward the hypothesis that hyperthyroidism, caused by fluoride exposure in their home country, is a cause of psychosis among immigrants from East Africa and other high-fluoride regions.

Hyperthyroidism is a persistent elevation of the blood levels of the thyroxin hormones T3 and T4, which are produced in the thyroid gland [7]. These hormones are notable for their high content of iodine; three atoms in each molecule of T3 and four in T4. Via a negative feedback mechanism the function of the thyroid gland is controlled by the thyroid stimulating hormone (TSH) from the pituitary gland. A suboptimal blood level of thyroid hormones stimulates the release of TSH, which in turn stimulates the thyroid gland to produce more of its hormones [7].

A chronic deficit of iodine causes a permanent reduction in the levels of thyroid hormones in the blood, a condition known as hypothyroidism. The resulting elevated level of TSH will increase the capacity of the thyroid gland to produce thyroxin, and sometimes also cause the thyroid gland to develop goitre [8]. If a person with an elevated capacity for production of thyroid hormones experiences an increased dietary intake of iodine, the thyroid gland will produce increased amounts of thyroid hormones, sometimes resulting in a shift from a hypothyroid to a hyperthyroid condition. An elevated capacity for thyroxin production and hyperthyroidism may occur even without a manifest goitre [7].

Hyperthyroidism is characterized by a number of physiological disturbances, including mental disorders. Some hyperthyroid patients develop behavioural problems, paranoia and an explosive temper [9], [10] and [11]. In spite of the characteristic and often dramatic symptoms, such a psychotic disturbance may be present for years without being properly diagnosed. The consequences can be tragic, involving for example broken marriages and serious violent crime.

The hypothesis

A high frequency of hyperthyroidism among immigrants from East Africa could be related to the chemical environment in their home countries. Large parts of East Africa are naturally very rich in fluoride, and local water sources frequently contain as much as 10 ppm [12] and sometimes up to 40 ppm [13] of fluoride. Fluoride is ingested especially via drinking water, but also via tea, fruits and vegetables [12]. While optimal water levels of fluoride (about 1 ppm) result in a good dental health, higher water levels as well as contribution from other sources, often cause dental fluorosis. The brown-spotted teeth that are characteristic of dental fluorosis occur very frequently in East Africa [13].

A substantial amount of evidence indicates that fluoride affects the thyroid gland [10], [13] and [14], and a high-fluoride intake may have similar effects as an iodine deficit [15]. Many independent investigators have published experimental data suggesting that fluoride reduces the production of thyroid hormones [8], and epidemiological data indicate a relation between high dietary fluoride intake and goitre [16] and [17]. Fluoride has even been used successfully to treat hyperthyroidism [18] and [19]. Hence, a high intake of fluoride may cause hypothyroidism and goitre in spite of an adequate intake of iodine [16] and [17]. The body responds by increasing the capacity to produce thyroid hormones, and due to this compensation people may have normal levels of thyroid hormones in spite of a permanent presence of inhibitory fluoride [13].

Several mechanisms have been proposed to explain the inhibitory effect of fluoride on thyroid hormones. The mechanism that has received most attention is related to the chemical similarity between fluorine and iodine. The elements are in the same group in the periodic table, but fluorine is the smallest and most reactive element. Fluoride may thus cause a competitive inhibition of the uptake of iodide in the thyroid gland, and reduce the production of thyroid hormones [13].

When people with a compensated fluoride-induced hypothyroidism move to a low-fluoride area, the fluoride-induced inhibition of the production of thyroid hormones ceases. In Scandinavia, the dietary intake of iodine is usually quite high due to iodized table salt and easy access to marine fish. Under these conditions, the elevated capacity for production of thyroid hormones may result in hyperthyroidism.

Evaluation of the hypothesis

The development of hyperthyroidism is a complex phenomenon, and a number of factors are likely to be involved. The experimental data are somewhat contradictory, in that not all studies on the effects of fluoride in humans and experimental animals have shown a clear effect [20]. Many vegetables and other foodstuffs may contain a variety of goitrogenic substances that interfere with thyroid metabolism [21], and these substances may sometimes act in combination with fluoride in man under natural conditions, but may not be included in laboratory experiments. Hence, the hypothesis does not imply that everybody who moves from a high-fluoride area will develop hyperthyroidism.

Consequences of the hypothesis

If the hypothesis is correct, people who move from a high-fluoride area to a low-fluoride area may have a physiological disposition for a hyperthyroid condition, and one may expect a substantially higher frequency of hyperthyroidism among people moving from high- to low-fluoride areas than among the native population of low-fluoride areas.

An increased frequency of hyperthyroidism among immigrants from high-fluoride regions is likely to be associated with an increased frequency of mental disorders such as psychosis [11]. Hyperthyroidism is easy to diagnose and treat, and much might be gained by an increased focus on the occurrence of hyperthyroidism-related psychosis among immigrants.

The diagnosis of a hyperthyroid condition among immigrants may be complicated by several factors. Persons with a compensated hypothyroidism are likely to show normal levels of thyroid hormones if they are tested when they arrive in their new country, and it may take several months before the symptoms of hyperthyroidism become conspicuous. If this is the case, hyperthyroidism may be ruled out as a cause of their problems without conducting new thyroid hormone measurements. Furthermore, people with manifest hyperthyroidism may not be motivated neither for a diagnostic investigation nor for treatment. Any suggestion that they may suffer from a hormonal disturbance is taken as another insult. It would therefore be useful if immigrants from high-fluoride areas were routinely made aware of the possibility of developing a hyperthyroid condition when they arrive in their new country.

Testing the hypothesis

We suggest the following approaches to test some aspects of the hypothesis:

1. Establish the frequency of hyperthyroidism among psychotic immigrants admitted to mental hospitals in Europe and see if the frequency is higher among immigrants from high-fluoride areas than among immigrants from other areas.
2. Compare immigrants from high- and low-fluoride areas as to their thyroid function parameters, thyroid size and nodular structure, at the time of arrival and again after about one year.
3. Establish the frequency of psychosis among 2nd generation immigrants, who have grown up in their new country, and who have the same social position as their parents, but a lower previous exposure to fluoride.

Acknowledgements

Authors want to thank Prof. Emer. Per Løkken, University of Oslo, for his comments on the manuscript.

References
[1] Mortensen PB, Cantor-Graae E, McNeil TF. Increased rates of schizophrenia among immigrants: some methodological concerns raised by Danish findings. Psychol Med 1997;27:813–20.

[2] Zolkowska K, Cantor-Graae E, McNeil TF. Increased rates of psychosis among immigrants to Sweden: is migration a risk factor for psychosis? Psychol Med 2001;31:669–78.

[3] Iversen VC, Morken G. Acute admissions among immigrants and asylum seekers to a psychiatric hospital in Norway. Soc Psychiatry Psychiatr Epidemiol 2003;38:515–9.

[4] Brugha T, Jenkins R, Bebbington P, Meltzer H, Lewis G, Farrell M. Risk factors and the prevalence of neurosis and psychosis in ethnic groups in Great Britain. Soc Psychiatry Psychiatr Epidemiol 2004;39:939–46.

[5] Lay B, Lauber C, Rössler W. Are immigrants at a disadvantage in psychiatric inpatient care? Acta Psychiatr Scand 2005;111:358–66.

[6] Cantor-Graae E, Zolkowska K, McNeil TF. Increased risk of psychotic disorder among immigrants in Malmö: a 3-year first-contact study. Psychol Med 2005;35:1155–63.

[7] Ganong WF. Review of medical physiology. 22nd ed. New York: Lange Medical; 2005.

[8] Galetti P-M, Joyet G. Effect of fluorine on thyroidal iodine metabolism in hyperthyroidism. J Clin Endocrinol Metab 1958;18:1102–10.

[9] Brownlie BEW, Rae AM, Walshe JWB, Wells JE. Psychoses associated with thyrotoxicosis – ‘thyrotoxic psychosis’. A report of 18 cases, with statistical analysis of incidence. Eur J Endocrinol 2000;142:438–44.

[10] Whynbrow PC, Bauer M. Behavioral and psychiatric aspects of thyrotoxicosis. In: Braverman LE, Utiger RD, editors. Werner & Ingbar’s the thyroid: a fundamental and clinical text. Philadelphia, PA: Lippincott; 2000. p. 673–8.

[11] Benvenga S, Lapa D, Trimarchi F. Don’t forget the thyroid in the etiology of psychoses. Am J Med 2003;115:159–60.

[12] Opinya GN, Bwibo N, Valderhaug J, Birkeland JM, Løkken P. Intake of fluoride through food and beverages by children in a high fluoride (9 ppm) area in Kenya. Discover Innovat 1991;3:71–5.

[13] Obel AOB. Goitre and fluorosis in Kenya. East Afr Med J 1982;59:363–5.

[14] Zhao W, Zhu H, Yu Z, Aoki K, Misumi J, Zhang X. Long-term effects of various iodine and fluorine doses on the thyroid and fluorosis in mice. Endocr Regul 1998;32:63–70.

[15] Anbar M, Guttmann S, Lewitus Z. Effect of monofluorosulphonate, difluorophosphate and fluoroborate ions on the iodine uptake of the thyroid gland. Nature 1959;183:1517–8.

[16] Day TK, Powell-Jackson PR. Fluoride, water hardness, and endemic goitre. Lancet 1972;1:1135–8.

[17] Jooste PL, Weight MJ, Kriek JA, Louw AJ. Endemic goitre in the absence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa. Eur J Clin Nutr 1999;53:8–12.

[18] Goldemberg L. Action physiologique des fluorures. Compt Rend Soc Physiol 1926;95:1169–72.

[19] May W. Die behandlung der hyperthyreosen einschliesslich des schweren genuinen Morbus Basedow mit fluor. Klin Wochenschr 1937;16:562–4.

[20] Bürgi H, Siebenhüner L, Miloni E. Fluorine and thyroid gland function: a review of the literature. Klin Wochenschr 1984;62:564–9.

[21] Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr 2006;26:293–322.