Lithium (Link Bibliography)

“Lithium” links:

  1. http://web.archive.org/web/20100227101156/http://www.jacn.org/cgi/content/full/21/1/14

  2. https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis

  3. https://www.discovermagazine.com/mind/lithium-the-brains-metal-marvel/

  4. 2008-shiotsuki.pdf: ⁠, Ippei Shiotsuki, Takeshi Terao, Hirochika Ogami, Nobuyoshi Ishii, Reiji Yoshimura, Jun Nakamura (2008-11-14; lithium):

    Background: In Japan, there are several resorts with cold springs that have mineral water containing relatively high levels of lithium compared to tap water. Visitors to such cold-spring resorts traditionally drink 2 to 4 L of mineral water for several hours in the early morning in the belief that the water has properties which maintain physical health. The present study aimed to investigate whether drinking the water increase serum lithium levels despite frequent urination, and to examine the mental effects of drinking mineral water containing lithium and related factors.

    Methods: 43 subjects who were not psychiatrically ill gave informed consent to this study. Before and just after drinking the water, serum lithium levels, the State-Trait of Anxiety Inventory (STAI) scores, Profiles of Mood States Test (POMS) scores and brain-derived neurotrophic factor (BDNF) levels were measured.

    Results: The subjects drank 3.64 L of the water in the early morning. Serum lithium levels were statistically-significantly increased from 0.026 to 0.073 mEq/​​​​L, which were much lower than the ones used in the treatment of psychiatric disorders. After drinking, most ratings of POMS statistically-significantly improved. Serum lithium levels were positively and statistically-significantly associated with serum BDNF levels, and changes in serum BDNF were negatively and statistically-significantly associated with changes in STAI state scores.

    Conclusion: The present findings suggest that drinking mineral water containing very low lithium levels may increase serum lithium levels and improve mental state as a likely consequence of changes in BDNF levels, although improvement in subjective well-being may have been due to placebo effect. Taking several methodological limitations into consideration, further studies are required to confirm this suggestion.

    [Keywords: lithium, mineral water, cold spring, STAI, POMS, BDNF]

  5. ⁠, Khairova, Rushaniya Pawar, Rohit Salvadore, Giacomo Juruena, Mario F. de Sousa, Rafael T. Soeiro-de-Souza, Márcio G. Salvador, Mirian Zarate, Carlos A. Gattaz, Wagner F. Machado-Vieira, Rodrigo (2012):

    Increased neuronal oxidative stress (OxS) induces deleterious effects on signal transduction, structural plasticity and cellular resilience, mainly by inducing lipid peroxidation in membranes, proteins and genes. Major markers of OxS levels include the thiobarbituric acid reactive substances (TBARS) and the enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase. Lithium has been shown to prevent and/​​​​or reverse DNA damage, free-radical formation and lipid peroxidation in diverse models. This study evaluates OxS parameters in healthy volunteers prior to and following lithium treatment. Healthy volunteers were treated with lithium in therapeutic doses for 2–4 weeks. Treatment with lithium in healthy volunteers selectively altered SOD levels in all subjects. Furthermore, a significant decrease in the SOD/​​​​CAT ratio was observed following lithium treatment, which was associated with decreased OxS by lowering hydrogen peroxide levels. This reduction in the SOD/​​​​CAT ratio may lead to lower OxS, indicated primarily by a decrease in the concentration of cell hydrogen peroxide. Overall, the present findings indicate a potential role for the antioxidant effects of lithium in healthy subjects, supporting its neuroprotective profile in bipolar disorder (BD) and, possibly, in neurodegenerative processes.

  6. https://web.archive.org/web/20100524065126/https://machineslikeus.com/news/how-lithium-works-brain

  7. http://neurosciencenews.com/lithium-prevents-brain-damage-parkinsons-disease/

  8. 2008-yeh.pdf: “Lithium may be useful in the prevention of Alzheimer’s disease in individuals at risk of presenile familial Alzheimer’s disease”⁠, Heng-Liang Yeh, Shih-Jen Tsai

  9. https://web.archive.org/web/20130113015023/http://www.vrp.com/stress/lithiums-potential-role-in-preventing-alzheimers-disease-mineral-benefits-other-conditions-besides-bipolar-disorder

  10. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/lithium-and-risk-for-alzheimers-disease-in-elderly-patients-with-bipolar-disorder/2F966D8BD1FF7E946C95949950AA61C1

  11. 2009-hampel.pdf

  12. 2006-terao.pdf

  13. 2005-dunn.pdf

  14. ⁠, William F. Parker, Rebecca J. Gorges, Y. Nina Gao, Yudong Zhang, Kwan Hur, Robert D. Gibbons (2018-07):

    Groundwater lithium concentrations were collected by the US Geological Survey from more than 3000 drinking water wells from 1992 to 2003…Claims data for 4,227,556 adults living in 174 counties were analyzed, including 3,046,331 with private insurance, 261,461 with Medicare Supplemental, and 919,764 with Medicaid. Among them, 404,662 patients (9.6%) lived in 1 of 32 counties with high lithium (>40 μg/​​​​L). The mean and median lithium concentrations were 27.4 μg/​​​​L and 11.1 μg/​​​​L, respectively (IQR, 3.7–23.6 μg/​​​​L).

    Unadjusted prevalence rates for all outcomes were statistically-significantly lower in high-lithium counties. However, high-lithium counties had fewer physicians and health care resources and had smaller, younger, less educated, and more Hispanic populations (Table).

    After adjustment for county-level demographics and health care resources, high lithium did not confer any statistically-significant benefit for bipolar disorder, dementia, or the negative controls major depressive disorder, myocardial infarction, or prostate cancer. The Figure shows the lack of any association across the entire lithium distribution.

    Discussion: Despite the substantial variation in groundwater lithium exposure in the United States, we found no statistically-significant association between groundwater lithium exposure and risk of bipolar disorder or dementia after adjustment for county-level demographics and health care resource. This indicates the purported association of high-lithium concentrations in drinking water with mental health disorders is driven by unaccounted variation in demographics, health care resources, and diagnosis practices.

    Therapeutic lithium doses are orders of magnitude larger than groundwater lithium concentrations, making a true causal relationship between groundwater lithium and mental health biologically dubious. In our study, the high-lithium group was exposed to a mean of 141.3 μg/​​​​L in their water supply. This means that a patient would need to drink more than 1000 L of water a day to ingest the lowest reported effective therapeutic lithium dose of 150 mg.

  15. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2649277

  16. http://www.neuroscience.cam.ac.uk/publications/download.php?id=11205

  17. 2015-vo.pdf

  18. 1990-schrauzer.pdf

  19. http://media.mercola.com/ImageServer/images/Thyroid/AnalysesToxicMetalsInHair.pdf

  20. 1995-klemfuss.pdf

  21. 1970-dawson.pdf

  22. 1972-dawson.pdf

  23. 2015-giotakos.pdf

  24. 1972-pokorny.pdf

  25. 2013-helbich.pdf: “GH_7_2 ORDINATO+_announcement⁠, .::Gold::.

  26. ⁠, Helbich, Marco Leitner, Michael Kapusta, Nestor D (2015):

    Background: Little is known about the effects of lithium intake through drinking water on suicide. This intake originates either from natural rock and soil elution and/​​​​or accumulation of lithium-based pharmaceuticals in ground water.

    Aims: To examine the interplay between natural lithium in drinking water, prescribed lithium-based pharmaceuticals and suicide in Austria.

    Method: Spatial Bayesian regressions for males, females and pooled suicide mortality rates were estimated.

    Results: Although the expected inverse association between lithium levels in drinking water and suicide mortality was confirmed for males and for total suicide rates, the relationship for females was not significant. The models do not indicate that lithium from prescriptions, assumed to accumulate in drinking water, is related to suicide risk patterns either as an individual effect or as a moderator of lithium levels in drinking water. Gender-specific differences in risk factors and local risk hot spots are confirmed.

    Conclusions: The findings do not support the hypotheses that lithium prescriptions have measureable protective effects on suicide or that they interact with lithium in drinking water.

  27. http://geospatialhealth.net/index.php/gh/article/download/20/20

  28. http://mic.com/articles/104096/there-s-a-suicide-epidemic-in-utah-and-one-neuroscientist-thinks-he-knows-why

  29. 2008-gonzalez.pdf

  30. 2008-servello.pdf⁠, Karla

  31. 2013-bluml.pdf: “Lithium in the public water supply and suicide mortality in Texas”⁠, Victor Blüml, Michael D. Regier, Gerald Hlavin, Ian R. H. Rockett, Franz König, Benjamin Vyssoki, Tom Bschor, Nestor D. Kapusta

  32. 1992-schrauzer.pdf

  33. 1983-walsh.pdf

  34. 2014-mauer.pdf: ⁠, Sivan Mauer, Derick Vergne, S. Nassir Ghaemi (2014-06-11; lithium):

    Objective: Dementia is a major public health issue, with notably high rates in persons with mood illnesses. Lithium has been shown to have considerable neuroprotective effects, even in trace or low doses. The aim of this review is to summarize the current understanding of lithium benefits in trace or low doses in dementia prevention and for other behavioral or medical benefits.

    Methods: A systematic review identified 24 clinical, epidemiological, and biological reports that met inclusion criteria of assessing lithium in standard or low doses for dementia or other behavioral or medical benefits.

    Results: 5 out of 7 epidemiological studies found an association between standard-dose lithium and low dementia rates. 9 out of 11 epidemiological studies, usually of drinking water sources, found an association between trace-dose lithium and low suicide/​​​​homicide/​​​​mortality and crime rates. All four small randomized clinical trials of lithium for Alzheimer’s dementia have found at least some clinical or biological benefits versus placebo. Only one small randomized clinical trial () of trace lithium has been conducted, assessing mood symptoms in former substance abusers, and found benefit with lithium versus placebo.

    Conclusions: Lithium, in both standard and trace doses, appears to have biological benefits for dementia, suicide, and other behavioral outcomes. Further RCT research of trace lithium in dementia is warranted.

    [Keywords: Cognition, dementia, lithium, prevention, standard dose, trace]

  35. 2014-vita.pdf

  36. https://www.isom.ca/wp-content/uploads/The-Role-of-Lithium-in-Neurological-Health-and-Disease-29.3.pdf

  37. https://www.nytimes.com/2014/09/14/opinion/sunday/should-we-all-take-a-bit-of-lithium.html

  38. 2020-barjastehaskari.pdf: “Relationship between suicide mortality and lithium in drinking water_ A systematic review and meta-analysis”⁠, Fateme Barjasteh-Askari, Mojtaba Davoudi, Homayoun Amini, Mohammad Ghorbani, Mehdi Yaseri, Masoud Yunesian, Amir Hossein Mahvi, David Lester

  39. 2020-memon.pdf: ⁠, Anjum Memon, Imogen Rogers, Sophie M. D. D. Fitzsimmons, Ben Carter, Rebecca Strawbridge, Diego Hidalgo-Mazzei, Allan H. Young (2020-07-27; lithium):

    Background: The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/​​​​depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population.

    Aims: To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates.

    Method: The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (ie. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects ⁠. The study was registered with PROSPERO (CRD42016041375).

    Results: The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/​​​​concentration in publicly available drinking water and total (pooled β = −0.27, 95% CI −0.47 to −0.08; p = 0.006, I2 = 83.3%), male (pooled β = −0.26, 95% −0.56 to 0.03; p = 0.08, I2 = 91.9%) and female (pooled β = −0.13, 95% CI −0.24 to −0.02; p = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/​​​​lower suicide mortality rates and lithium levels/​​​​concentration.

    Conclusions: This synthesis of ecological studies, which are subject to the ecological fallacy/​​​​bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.

  40. 2020-eyrewatt.pdf: ⁠, Brenton Eyre-Watt, Eesharnan Mahendran, Shuichi Suetani, Joseph Firth, Steve Kisely, Dan Siskind (2020-10-13; lithium):

    Background: Lithium in drinking water may have substantial mental health benefits. We investigated the evidence on the association between lithium concentrations in drinking water and their neuropsychiatric outcomes.

    Methods: We conducted a systematic review and meta-analysis and searched Pubmed, Embase, Web of Science, PsycINFO and CINAHL up to 19 January 2020, for peer-reviewed research examining the association between lithium concentrations in drinking water and neuropsychiatric outcomes. We used a pairwise analysis and a random effects model to meta-analyse suicide rates and psychiatric hospital admissions. We assessed for publication bias using Egger’s test and Duval and Tweedie’s Trim and Fill analysis.

    Results: Twenty-seven studies including 113 million subjects were included in this systematic review. Meta-analysis of 14 studies including 94 million people found higher lithium concentrations were associated with reduced suicide rates (r =  −0.191, 95% confidence interval = [−0.287, −0.090], p < 0.001) and meta-analysis of two studies including 5 million people found higher lithium concentrations were associated with fewer hospital admissions (r = −0.413, 95% confidence interval = [−0.689, −0.031], p =  0.035). We found statistically-significant heterogeneity between studies (Q = 67.4, p < 0.001, I2 = 80.7%) and the presence of publication bias (Egger’s test; t value = 2.90, p = 0.013). Other included studies did not provide sufficient data to analyse other neuropsychiatric outcomes quantitatively.

    Conclusion: Higher lithium concentrations in drinking water may be associated with reduced suicide rates and inpatient psychiatric admissions. The relationship with other neuropsychiatric outcomes and complications remains unclear. Further research is required before any public health recommendations can be made.

    Trial registration number: The study was registered with PROSPERO, number CRD42018090145.

    [Keywords: Neuropsychiatric outcomes, lithium, drinking water, suicide, public health]

  41. 2009-ohgami.pdf: ⁠, Hirochika Ohgami, Takeshi Terao, Ippei Shiotsuki, Nobuyoshi Ishii, Noboru Iwat (2009-05-01; lithium):

    Although lithium is known to prevent suicide in people with mood disorders, it is uncertain whether lithium in drinking water could also help lower the risk in the general population. To investigate this, we examined lithium levels in tap water in the 18 municipalities of Oita prefecture in Japan in relation to the suicide standardised mortality ratio (SMR) in each municipality. We found that lithium levels were statistically-significantly and negatively associated with SMR averages for 2002–2006. These findings suggest that even very low levels of lithium in drinking water may play a role in reducing suicide risk within the general population.

  42. 2009-terao.pdf: “Even very low but sustained lithium intake can prevent suicide in the general population?”⁠, Takeshi Terao, Shinjiro Goto, Masatoshi Inagaki, Yasumasa Okamoto

  43. https://www.mdpi.com/1660-4601/10/11/6044/pdf

  44. ⁠, Prabha S. Chandra, Girish N. Babu (2018-01-02):

    The study by Ohgami et al 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.

    First, 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 levels between men and women (with the results being less statistically-significant in women) is one such example. 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 at least some of these is a major limitation of the study. Second, although we agree with Young 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 function, pregnant women 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/​​​​1 in one study, but there are no data about serum lithium levels among individuals attempting suicide. Maybe assessment of serum lithium levels among those with suicidal behaviour can be a place to start. More data are also needed on the role of low-dose lithium in individuals without mood disorders who are at risk of suicide.

    Finally, several foods (particularly spices) are known to have relatively high levels of lithium as reported by a study in India several years ago. This study reported levels as high as 12 μg/​​​​g of lithium in tobacco and high levels in crude salt, rock salt and several spices. Maybe, until such time that we are certain about lithium’s role in decreasing suicidality in non-psychiatric populations, it might be worth conducting randomised controlled trials with these foods in individuals with suicidal behaviour to see whether low doses of lithium really help.

    Let us not throw the lithium out with the tap water yet!

  45. 2011-schopfer.pdf

  46. 2015-ishii.pdf

  47. 2016-shiotsuki.pdf: “Trace lithium is inversely associated with male suicide after adjustment of climatic factors”⁠, Ippei Shiotsuki, Takeshi Terao, Nobuyoshi Ishii, Shouhei Takeuchi, Yoshiki Kuroda, Kentaro Kohno, Yoshinori Mizokami, Koji Hatano, Sanshi Tanabe, Masayuki Kanehisa, Noboru Iwata, Shinya Matusda

  48. 2020-kugimiya.pdf: ⁠, Tsuyoshi Kugimiya, Nobuyoshi Ishii, Kentaro Kohno, Masayuki Kanehisa, Koji Hatano, Hirofumi Hirakawa, Takeshi Terao (2020-08-11; lithium):

    Objectives: The aims of the present study thus were (a) to further investigate the association between lithium levels in drinking water and suicide rates by adjusting relevant factors using the so far largest available dataset in Japan, (b) to confirm sex differences, (c) to estimate the effects of long-term exposure to trace lithium, (d) to investigate the effects of drinking bottled instead of tap water, and (e) to exploratorily investigate which lithium levels may be associated with lower suicide rates.

    Methods: Mean lithium levels in drinking water of all 808 cities and wards (ie, 785 cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to mean suicide standardized mortality ratios (SMRs) during the 7 years from 2010 to 2016. Multiple regression analyses adjusted for the size of each population were used to investigate the association of lithium levels with suicide SMRs with adjustments for relevant factors.

    Results: The adjusted model showed statistically-significant inverse associations of lithium levels with total and male SMRs, but not with female SMRs. Neither the proportion of residents who continued to live in the same city nor the consumption of bottled water changed the association between lithium levels and suicide SMRs. Finally, it was 30 μg/​​​​L or more that was associated with lower suicide SMRs.

    Conclusions: The present findings reconfirm the inverse association between lithium levels in drinking water and suicide rates particularly in the male population.

  49. ⁠, Naomi Kozaka, Shouhei Takeuchi, Nobuyoshi Ishii, Takeshi Terao, Yoshiki Kuroda (2020-06-27):

    Background: Most studies have reported that suicide mortality rates are negatively associated with lithium levels in tap water; however, a few studies showed either no association or a positive association. Thus, the association between suicide mortality and lithium levels in tap water remains controversial. To clarify the association, our study evaluated the association between lithium levels in tap water and suicide mortality rates in Miyazaki Prefecture of Japan, after adjusting for factors.

    Methods: We measured lithium levels in tap water across the 26 municipalities of Miyazaki Prefecture in Japan. We examined the standardized mortality ratio (SMR) for suicide in each municipality and used the data as the average suicide SMRs over 5 years (2009–2013). Weighted least-squares regression analysis, adjusted for the size of each municipality’s population, was used to investigate the association between lithium levels in tap water and suicide SMRs. In addition to a crude model, in an adjusted model, potential confounding factors (proportion of elderly people, proportion of one-person households, annual marriage rate, annual mean income, unemployment rate, the density of medical doctors per 100,000 people, annual total rainfall, and proportion of people with a college education or higher) were added as covariates.

    Results: We showed that male and female suicide SMRs were not associated with lithium levels in tap water in Miyazaki Prefecture. After adjusting for confounders, male suicide SMRs were statistically-significantly and positively associated with the proportion of elderly people in the population and annual total rainfall, and female suicide SMRs were associated with the proportion of elderly people in the population.

    Conclusions: No association between lithium levels in tap water and suicide mortality rates was found in Miyazaki Prefecture.

  50. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/lithium-in-drinking-water-and-suicide-mortality/681D92C1B8FF112958A92C2D6D373F80

  51. https://www.biomedcentral.com/content/pdf/1476-072X-11-19.pdf

  52. 2015-helbich.pdf

  53. 2013-giotakos.pdf

  54. https://link.springer.com/article/10.1007%2Fs40211-017-0222-5

  55. 2017-liaugaudaite.pdf: ⁠, Vilma Liaugaudaite, Narseta Mickuviene, Nijole Raskauskiene, Rima Naginiene, Leo Sher (2017-09-01; lithium):

    • The suicide-protective property of natural lithium was confirmed with a positive effect for men.
    • Higher lithium levels in drinking water might have a protective effect on the risk of suicide in men.
    • Evaluation of lithium in a local drinking water, might provide regional effective prevention programs.

    Suicide is a major public health concern affecting both the society and family life. There are data indicating that higher level lithium intake with drinking water is associated with lower suicide rate. This pilot study examined the relationship between lithium levels in drinking water and suicide rates in Lithuania.

    22 samples from public drinking water systems were taken in 9 cities of Lithuania. The lithium concentration in these samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The suicide data were obtained from the Lithuania Database of Health Indicators, and comprised all registered suicides across all ages and gender within the 5-year period from 2009 to 2013.

    The study demonstrated an inverse correlation between levels of lithium (log natural transformed), number of women for 1000 men and standardized mortality rate for suicide among total study population. After adjusting for confounder (the number of women for 1000 men), the lithium level remained statistically-significant in men, but not in women.

    Our study suggested that higher levels of lithium in public drinking water are associated with lower suicide rates in men. It might have a protective effect on the risk of suicide in men.

  56. 2019-liaugaudaite.pdf: “Inverse relationship between lithium levels in drinking water and suicide rates”⁠, V. Liaugaudaite, R. Naginiene, N. Raskauskiene, N. Mickuviene, A. Bunevicius, L. Sher

  57. 2018-palmer.pdf: ⁠, Anna Palmer, Marshall E. Cates, Greg Gorman (2018; lithium):

    Background: Recent studies have shown that lithium may be effective at reducing suicide at low doses, such as those found in drinking water.

    Aims: The purpose of this study was to compare suicide rates with natural lithium levels in the drinking water of various Alabama counties.

    Method: Five drinking water samples from each of 15 Alabama counties were collected. Lithium levels were measured in triplicate using an inductively coupled plasma emission spectrophotometer and compared with suicide rate data for the period 1999–2013. Age, gender, and poverty were evaluated as potential confounding variables.

    Results: The average measured lithium concentrations ranged from 0.4 ppb to 32.9 ppb between the counties tested. The plot of suicide rate versus lithium concentration showed a statistically-significant inverse relationship (r = −0.6286, p = 0.0141). Evaluation of male-only suicide rate versus lithium concentration data also yielded statistically-significant results; however, the female-only rate was not statistically-significant. Age standardized suicide rates and poverty when individually compared against lithium levels were also found to be statistically-significant; unexpectedly, however, poverty had a parallel trend with suicide rate.

    Conclusion: Lithium concentration in drinking water is inversely correlated with suicide rate in 15 Alabama counties.

  58. 2014-neves.pdf

  59. https://www.actamedicaportuguesa.com/revista/index.php/amp/article/viewFile/10744/5596

  60. 2021-steinmetz.pdf: ⁠, Lorena Cecilia López Steinmetz, Romina Lucrecia, López Steinmetz, Silvina Laura Diaz, Juan Carlos Godoy (2021-02-01; lithium):

    The Lithium Triangle in the Andean plateau involves high altitude (>3,000 m asl) hydrological systems having high lithium graded waters. This research was carried-out in rural areas of north westernmost Argentinean Andes and was aimed: (1) to determine concentrations of lithium in drinking waters; (2) to calculate suicide mortality rates based on available official data (2003–2013); (3) to analyze bivariate differences between lithium concentrations in drinking water, mean rates of suicide mortality, altitude of sampling sites, and water sources; (4) to analyze bivariate correlations between lithium concentrations in drinking water, mean rates of suicide mortality, and altitude; (5) to test predictive models for mean rates of suicide mortality, when considering the predictors lithium concentrations in drinking water, altitude, and water sources.

    Lithium determinations in drinking waters were performed by Microwave Plasma-Atomic Emission Spectrometer. Nonparametric tests were applied to analyze differences and correlations. Generalized linear models (GLM) were used to fitting models for mean rates of suicide. Drinking waters contained up to 2.98 mg L−1 of lithium. Mean rates of suicide mortality (per 100,000 inhabitants) were high, ranging from 19.12 (± 19.83) to 30.22 (± 16.70). Lithium but not altitude was positively correlated with suicide mortality when analyzing bivariate correlations (Li: ρ = 0.76, p < 0.001). However, when GLM were calculated, a statistically-significant interaction effect was found between lithium and altitude (p < 0.001). This interaction effect would act in some way restraining the suicide mortality rates.

    [Keywords: lithium in drinking water, altitude, suicide, rural populations, Andes, Argentina]

  61. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/lithium-in-drinking-water-and-suicide-rates-across-the-east-of-england/BC6643432106E7DB1AF4C05A1C888BE9

  62. 2015-pompili.pdf: “IWBP_A_1062551.indd⁠, Maurizio Pompili, Monica Vichi, Enrico Dinelli, Roger Pycha, Paolo Valera, Stefano Albanese, Annamaria Lima, Benedetto De Vivo, Domenico Cicchella, Andrea Fiorillo, Mario Amore, Paolo Girardi, Ross J. Baldessarini

  63. ⁠, Nikoline N. Knudsen, Jörg Schullehner, Birgitte Hansen, Lisbeth F. Jørgensen, Søren M. Kristiansen, Denitza D. Voutchkova, Thomas A. Gerds, Per K. Andersen, Kristine Bihrmann, Morten Grønbæk, Lars V. Kessing, Annette K. Ersbøll (2017-06-10):

    Suicide is a major public health concern. High-dose lithium is used to stabilize mood and prevent suicide in patients with affective disorders. Lithium occurs naturally in drinking water worldwide in much lower doses, but with large geographical variation. Several studies conducted at an aggregate level have suggested an association between lithium in drinking water and a reduced risk of suicide; however, a causal relation is uncertain.

    Individual-level register-based data on the entire Danish adult population (3.7 million individuals) from 1991 to 2012 were linked with a moving 5-year time-weighted average (TWA) lithium exposure level from drinking water hypothesizing an inverse relationship. The mean lithium level was 11.6 μg/​​​​L ranging from 0.6 to 30.7 μg/​​​​L. The suicide rate decreased from 29.7 per 100,000 person-years at risk in 1991 to 18.4 per 100,000 person-years in 2012.

    We found no statistically-significant indication of an association between increasing 5-year TWA lithium exposure level and decreasing suicide rate. The comprehensiveness of using individual-level data and spatial analyses with 22 years of follow-up makes a pronounced contribution to previous findings.

    Our findings demonstrate that there does not seem to be a protective effect of exposure to lithium on the incidence of suicide with levels below 31 μg/​​​​L in drinking water.

    [Keywords: drinking water, lithium, suicide, individual-level data, spatial analysis, Denmark, exposure assessment]

  64. http://pure.au.dk/portal/en/publications/low-risk-of-suicide-and-lithium-in-drinking-water-a-danish-individuallevel-cohort-study-using-spatial-analysis(5855ed41-d812-4ce4-b089-078be11c11fa).html

  65. 2005-cipriani.pdf: ⁠, Andrea Cipriani, Heather Pretty, Keith Hawton, John R. Geddes (2005-10-01; lithium):

    Objective: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder.

    Method: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966–June 2002), EMBASE (1980–June 2002), CINAHL (1982–March 2001), PsycLIT (1974–June 2002), PSYNDEX (1977–October 1999), and LILACS (1982–March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term “lithium” for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors.

    Results: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio = 0.26; 95% confidence interval [CI] = 0.09–0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio = 0.21; 95% CI = 0.08–0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio = 0.42, 95% CI = 0.21–0.87).

    Conclusions: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.

  66. http://lefnet.hu/resources/userfiles/file/Rihmer/Baldessarini%20-suic.%20pr.%2006.pdf

  67. 2007-guzzetta.pdf: “Lithium Treatment Reduces Suicide Risk in Recurrent Major Depressive Disorder”⁠, Guzzetta, et al

  68. https://link.springer.com/content/pdf/10.1186%2Fs40345-015-0032-2.pdf

  69. 2011-zarse.pdf

  70. 2018-fajardo.pdf: ⁠, Val A. Fajardo, Paul J. LeBlanc, Val Andrei Fajardo (2018; lithium):

    Lithium in tap water was previously found to have life-extending effects across 18 Japanese municipalities. Using a larger dataset with several Texas counties, our study shows that lithium concentrations in tap water are negatively associated with all-cause mortality (r = −0.18, p = 0.006, 232 counties) and years of potential life lost (r = −0.22, p = 0.001, 214 counties). Thus, our present findings extend and reinforce lithium’s purported life-prolonging effect in humans.

  71. http://www.jhsph.edu/research/centers-and-institutes/george-w-comstock-center-for-public-health-research-and-prevention/pdfs_1965-1978/76Oliver%20SL_1976_Arch%20Environ%20Health.pdf

  72. 2019-schullehner.pdf: “Lithium in drinking water associated with adverse mental health effects”⁠, Jörg Schullehner, Diana Paksarian, Birgitte Hansen, Malene Thygesen, Søren Munch Kristiansen, Søren Dalsgaard, Torben Sigsgaard, Carsten Bøcker Pedersen

  73. 2017-ando.pdf

  74. 2018-shimodera.pdf: “Lithium levels in tap water and psychotic experiences in a general population of adolescents”⁠, Shinji Shimodera, Shinsuke Koike, Shuntaro Ando, Syudo Yamasaki, Ryosuke Fujito, Kaori Endo, Yudai Iijima, Yu Yamamoto, Masaya Morita, Ken Sawada, Nobuki Ohara, Yuji Okazaki, Atsushi Nishida

  75. https://www.jstage.jst.go.jp/article/cnpt/8/0/8_7/_pdf

  76. 2017-matsuzaki.pdf: “Re-analysis of the association of temperature or sunshine with hyperthymic temperament using lithium levels of drinking water”⁠, Hideki Matsuzaki, Takeshi Terao, Takeshi Inoue, Yoshikazu Takaesu, Nobuyoshi Ishii, Kentaro Kohno, Minoru Takeshima, Hajime Baba, Hiroshi Honma

  77. 1993-schrauzer.pdf: “effects of nutritional lithium supplementation on Mood.pdf”

  78. #shiotsuki-et-al-2008

  79. https://clinicaltrials.gov/ct2/show/record/NCT01257867

  80. https://psychotropical.info/lithium-in-diet-and-body-1/

  81. #chandra-babu-2018

  82. 2013-lucas.pdf

  83. Replication

  84. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2011/the-economics-of-health-care-reform

  85. https://www.nytimes.com/2013/07/02/magazine/the-half-trillion-dollar-depression.html?pagewanted=all

  86. http://io9.com/5827381/heres-what-it-actually-costs-to-run-a-university-science-lab

  87. http://www.mercurynews.com/health/ci_18361882

  88. https://www.nature.com/articles/nbt.1837

  89. https://www.pnas.org/content/105/6/2052.full

  90. http://scholar.google.com/scholar?q=lithium+cognition

  91. 2008-macdonald.pdf

  92. ⁠, Broberg, Karin Concha, Gabriela Engström, Karin Lindvall, Magnus Grandér, Margareta Vahter, Marie (2011):

    Background: High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function.

    Objectives: We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function.

    Methods: Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T4) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods.

    Results: The median urinary lithium concentration was 3,910 μg/​​​​L (5th, 95th percentiles, 270 μg/​​​​L, 10,400 μg/​​​​L). Median plasma concentrations (5th, 95th percentiles) of T4 and TSH were 17 pmol/​​​​L (13 pmol/​​​​L, 21 pmol/​​​​L) and 1.9 mIU/​​​​L, (0.68 mIU/​​​​L, 4.9 mIU/​​​​L), respectively. Urine lithium was inversely associated with T4 [β for a 1,000-μg/​​​​L increase=-0.19; 95% confidence interval (CI), -0.31 to -0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T4, β=-0.17; 95% CI, -0.32 to -0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T4 (adjusted T4 for a 1 μg/​​​​L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006).

    Conclusions: Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.

  93. 2014-aprahamian.pdf

  94. 2017-kessing.pdf

  95. https://osf.io/x4fk3/

  96. Iodine

  97. https://www.usgs.gov/special-topic/water-science-school/science/total-water-use-united-states

  98. ⁠, McCollister, Kathryn E. French, Michael T. Fang, Hai (2010):

    Estimating the cost to society of individual crimes is essential to the economic evaluation of many social programs, such as substance abuse treatment and community policing. A review of the crime-costing literature reveals multiple sources, including published articles and government reports, which collectively represent the alternative approaches for estimating the economic losses associated with criminal activity. Many of these sources are based upon data that are more than 10 years old, indicating a need for updated figures. This study presents a comprehensive methodology for calculating the cost to society of various criminal acts. Tangible and intangible losses are estimated using the most current data available. The selected approach, which incorporates both the cost-of-illness and the jury compensation methods, yields cost estimates for more than a dozen major crime categories, including several categories not found in previous studies. Updated crime cost estimates can help government agencies and other organizations execute more prudent policy evaluations, particularly benefit-cost analyses of substance abuse treatment or other interventions that reduce crime.

  99. Forking-Paths

  100. https://www.vox.com/future-perfect/2018/10/24/18010592/future-perfect-podcast-lithium-drinking-water-suicide