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eLetters: Electronic letters published:
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Lithium levels and risk of suicide in general population
- Prabha S Chandra, Girish N Babu (18 June 2009)
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Lithium in drinking water and diet and suicide rates
- Geetha Desai, Santosh K Chaturvedi (18 June 2009)
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Authors' reply
- Takeshi Terao, Hirochika Ohgami, Ippei Shiotsuki, Nobuyoshi Ishii, and Noboru Iwata (1 July 2009)
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Confounding the "lithium waters"
- Mark A Huthwaite, James Stanley,PhD, Biostatistician, Department of Public Health, University of Otago, Wellington, New Zealand (22 October 2009)
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Reply to Drs Huthwaite and Stanley
- Takeshi Terao, Hirochika Ohgami, Ippei Shiotsuki, Nobuyoshi Ishii, Oita University Faculty of Medicine, Noboru Iwata, Hiroshima International University (10 November 2009)
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Prabha S Chandra, professor of psychiatry National Institute of Mental Health & Neurosciences, Bangalore, Girish N Babu
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prabhasch{at}gmail.com Prabha S Chandra, et al.
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The study by Ohgami H et al (2009) on the association of lithium in tap water and suicide rates raises serious ethical issues related to the interpretation of research findings and as a consequence their possible application. While not denying that the findings are interesting and have caused a stir in the lay press and on the internet, we question the methodology and the possible implications if the results are taken seriously. Firstly, sociological reasons for suicide are important and changing rates of suicide in many countries are linked to changes such as migration, poverty, relationships and economic issues. The finding that when gender was included in the analysis, there was a difference in the significance levels between men and women (with the results being less significant in women) are one such evidence. Adding lithium to tap water is not going to change these demographic and social factors that contribute to suicide rates and not having accounted for atleast some of these is a major limitation of the study. Secondly, while we agree with Young (2009) in his commentary that more research is needed to prove or disprove this tantalizing idea, it is also important to assess what the impact of different levels of tap water lithium is going to be on thyroid functions, on pregnant mothers and on the unborn fetus. It is also important to assess whether tap water levels of lithium directly correlate with serum lithium levels in the respective populations. The levels of lithium in body fluids in normal healthy controls have varied from 0.01 to 0.09 meq/l in one study3 but there is no data about serum lithium levels among persons attempting suicide. Maybe assessment of serum lithium levels among persons with suicidal behavior can be a place to start. More data is also needed on the role of low dose lithium on non mood disordered individuals with suicidality. Finally, several foods (particularly spices) are known to have relatively high levels of lithium as reported by a study done in India several years ago3. This study reported levels as high as 12 µg/gm of lithium in tobacco and high levels in crude salt, rock salt and several spices. Maybe, till such time that we are uncertain about lithium’s role in decreasing suicidality in non psychiatric populations, it might be worth conducting randomized controlled trials with these foods in individuals with suicidal behavior to see if low doses of lithium really help. Let us not throw the lithium with the tap water yet! 1. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. Br J Psychiatry 2009; 194: 464–5. 2. Young AH Invited commentary on . . . Lithium levels in drinking water and risk of suicideThe British Journal of Psychiatry (2009) 194, 466-5. 3. Jathar VS, Pendharkar PR, Pandey VK, Raut SJ, Doongaji DR, Bharucha MP & Satoskar RS. Manic depressive psychosis in India and the possible role of lithium as a natural prophylactic. II--Lithium content of diet and some biological fluids in Indian subjects. 1980; 26 (1): 39-44. Declaration of interest: None. |
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Geetha Desai, Consultant Psychiatrist National Institute of Mental Helath and Neurosciences, Bangalore, India, Santosh K Chaturvedi
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desaigeetha{at}gmail.com Geetha Desai, et al.
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Ohgami et al.1 reported lithium in tap water (0.7 - 59 µgm/L) and linked lithium in drinking water to suicide rates. However, dietary lithium, which has received scant attention, is available from grains and vegetables and to some extent animal derived foods 2. Hence, considering only drinking water lithium may not be enough to link with suicide rates. Dietary sources of lithium may actually have made the difference rather than just the drinking water. Differences in prevalence of mood disorders with natural lithium levels acting as a prophylactic against were reported 3,4. The report3 assessed the lithium content of diet [72.55-154.6 µgm] and biological fluids and hypothesized lithium to be the natural prophylactic. It will be interesting to see if there are differences in prevalence rates of mood disorders, which can explain the variation in suicide rates, with lithium in diet as well as tap water. And what about lithium containing food cooked in lithium containing tap water ?! References 1. Ohgami H, Teao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking wate and rates of suicide. Br J Psychiatry 2009, 194, 464-5. 2. Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 2002; 21: 14–21. 3. Jathar VS, Pendharkar PR, Pandey VK, Raut SJ, Doongaji DR, Bharucha MP, Satoskar RS. Manic depressive psychosis in India and the possible role of lithium as a natural prophylactic. II--Lithium content of diet and some biological fluids in Indian subjects. J Postgrad Med 1980; 26: 39-44 4. Doongaji DR, Jathar VS, Satoskar RS. Manic depressive psychosis in India and the possible role of lithium as a natural prophylactic. I-- Hypothesis. J Postgrad Med 1980; 26: 34-38. [Declaration of Interest : None] |
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Takeshi Terao, Professor Department of Neuropsychiatry, Oita University Faculty of Medicine, Hirochika Ohgami, Ippei Shiotsuki, Nobuyoshi Ishii, and Noboru Iwata
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terao{at}med.oita-u.ac.jp Takeshi Terao, et al.
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Although we thank Drs Chandra and Babu for their comments, we would like to emphasize that we had never recommended lithium addition to drinking water supplies in our short report (1) because at the moment our findings are preliminary and yet to be conclusive. We respond to their comments as follows. Firstly, they pointed out that sociological factors such as migration, poverty, human relations and economic issues may be associated with suicide rates. We agree with them and have already admitted such limitation by stating “other factors such as psychosocial and economic factors were not taken into consideration” in our report (1). Secondly, they stated that it is also important to assess side effects of lithium in tap water on thyroid function, pregnant mothers and unborn fetus. Although it seems probable that these low levels of lithium are far below the levels required to produce such side effects of lithium, we agree with them. Thirdly, they pointed out lithium in several foods, which was also stated by Drs Desai and Chaturvedi. This may be important because dietary lithium intakes were estimated to be not a negligible quantity. For example, they were reported to be 1560±980 (China, Xi’an), 1485±1009 (Mexico, Tijuana), 1090±324 (Sweden, Stockholm), 1009±324 (Denmark, Copenhagen), 939±928 (Mexico, Culiacan), 821±684 (USA, Texas), 812±383 (Japan, Tokyo), 650±740 (USA, New York), 429±116 (USA, San Diego), 406±383 (Germany, Munich), and 348±290 µg/day (Austria, Vienna)(2). Therefore, at the next stage, it seems necessary to measure serum lithium levels of the residents, which can totally assess lithium intake in the form of both drinking water and foods. 1. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. British Journal of Psychiatry, 2009; 194; 464-465. 2. Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. Journal of The American College of Nutrition, 2002; 21: 14-21. | |||
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Mark A Huthwaite, FCPsych (SA) Department of Psychological Medicine, University of Otago, Wellington, New Zealand, James Stanley,PhD, Biostatistician, Department of Public Health, University of Otago, Wellington, New Zealand
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mark.huthwaite{at}otago.ac.nz Mark A Huthwaite, et al.
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In their short report, Ohgami et al1 reported lithium levels in drinking water and linked it to the risk of suicide. Despite the report highlighting the pitfalls of drawing simple conclusions from large-scale ecological studies, a Google search shows that these findings have been widely disseminated in scientific and lay media. A major concern, addressed only obliquely by the authors, is the likelihood of confounding in this scenario. As noted by Chandra and Babu 3 sociological factors play an important role in suicide. The lack of accounting for such potential confounders for the different districts in the study is a serious methodological omission, rendering the results of the study untenable from an epidemiological perspective. The demographics of the different areas (beyond age structure) are not addressed, thus ignoring important economic and social factors (like deprivation and unemployment) which contribute to suicide risk. Adjusting for differences in age structures between centres using standardized mortality ratios (SMRs) is unlikely to account for all important sources of confounding, so that the possibility of residual confounding must be considered a major qualifier when considering these results, rather than details to be addressed in future studies 2 . The potential reasons behind difference in lithium levels in the drinking water samples in the different municipalities are also not explained. Lithium levels in water sampled across a number of districts in New Zealand reveals differences within municipal areas, depending where the sample is sourced. In this context, how valid is it then to use the mean value to represent the lithium exposure in that area? This would require the matching of lithium levels with suicide data from each discrete area of water supply and a loss of statistical power for such a relatively uncommon event as suicide. The duration of exposure to a specific level of lithium in the drinking water was also not addressed . Apart from the issue of dietary intake of lithium noted in the letter by Desai and Chaturvedi4 there is also the question of where people source most of their drinking water and the use of bottled water? In the context of the short report, it is also difficult to fully assess the suitability of the analysis methods used. It would have been useful to have more detail on the weighting structure used in the regression, alongside frequency data on the number of events observed in each locality. Also, the reported beta coefficient from the regression is not interpretable in the context of the presented figure or reported analysis methods. While the reported results were indeed intriguing, in the absence of more a developed approach to the research question it seems too early, and indeed misleading for a non-scientist audience, to even start speculating on the relationship between suicide rates and lithium in drinking water sources on the basis of these data. In this era of rapid information dissemination the publishing of reports without rigorous scrutiny of the statistical method and due consideration of the confounding variables is a concern. 1. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. Br J Psychiatry 2009; 194: 464-5. 2. Young AH. Invited commentary on … Lithium levels in drinking water and risk of suicide. Br J Psychiatry 2009; 194: 466 3. Chandra and Babu. Correspondence: Lithium in drinking water and food, and risk of suicide. Br J Psychiatry 2009; 195.3.271a 195.3.271. 4. Desai and Chaturvedi. Correspondence: Lithium in drinking water and food, and risk of suicide Br J Psychiatry 2009; 195.3.271. |
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Takeshi Terao, Professor Oita University Faculty of Medicine, Hirochika Ohgami, Ippei Shiotsuki, Nobuyoshi Ishii, Oita University Faculty of Medicine, Noboru Iwata, Hiroshima International University
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terao{at}med.oita-u.ac.jp Takeshi Terao, et al.
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We thank Drs Huthwaite and Stanley for their letter to our short report (1) and would like to reply as follows. 1) They pointed out that a major concern is the likelihood of confounding in this scenario. In our previous research (2), we examined government statistics on suicide of the 47 prefectures in Japan. The overall yearly suicide rate in Japan was 25 per 100,000 population in 1999. Pearson's correlation was used to calculate correlations of suicide rate with latitude, longitude, yearly mean temperature, yearly total sunshine, yearly mean individual income, and yearly unemployment rate in the 47 prefectures, although lithium levels were not measured in the study. There was a significant correlation with suicide rate for yearly total sunshine, yearly mean temperature, latitude, and yearly mean individual income. By using multiple regression analysis, yearly total sunshine was the only individual variable to predict significant variance in suicide rate. Taking these findings into consideration, we did not use yearly mean individual income or yearly unemployment rate (1). Also, yearly total sunshine was similar between the 18 municipalities of Oita prefecture and we did not use this. Most importantly, only 18 municipalities prevented us from further analyses including confounding factors. We are now planning to perform a large study to consider confounding factors. 2) They stated that the potential reasons behind difference in lithium levels in the drinking water samples in the different municipalities are also not explained and asked how valid it is then to use the mean value to represent the lithium exposure in that area. Lithium levels of drinking water supplier were measured at 26 locations in Oita city and at 53 locations in the other municipalities. The reason for the large difference in lithium levels is unknown, but Oita prefecture may have different geological features between the 18 municipalities and such difference may bring about large difference in lithium levels although this thought is speculative. Also, instead of the mean value, we used the median value for the analysis and the similar results were obtained. 3) They asked the duration of exposure to a specific level of lithium in the drinking water and where people source most of their drinking water and the use of bottled water. In Japan, most people drink tap water although a small portion of people drink bottled water. Therefore, it is meaningful to measure lithium levels in tap water supplier. Moreover, the duration of exposure to a specific level of lithium is unknown but if the residents continue to live at the same place, then their age may be associated with the duration. 4) They said that in the context of the short report it is also difficult to fully assess the suitability of the analysis methods used. We agree with them. Nonetheless, we believe that short report itself is not conclusive but can provide new findings which leads to comprehensive research to establish a definite conclusion. We would like readers to read a short report as such, which can prevent misleading. Declaration of Interest: None 1. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. Br J Psychiatry 2009; 194: 464-5. 2. Terao T, Soeda S, Yoshimura R, Nakamura J, Iwata N. Effect of latitude on suicide rates in Japan. Lancet 2002; 360: 1892. |
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