Photography's Underappreciated Contributions to Neuropsychiatry: The Photographs of W. Eugene Smith in Minamata, Japan.

Photographers and filmmakers have made important contributions to the international mental health community through documentation and social commentary, leveraging the power of visual imagery. To illustrate, this article uses the example of W. Eugene Smith who photographed the catastrophic effects of methylmercury poisoning from industrial pollution in the region around Minamata Bay, Japan. Although many art forms have been comfortably integrated into mainstream psychiatry and neuropsychiatry, photography has been underappreciated and underutilized.

Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality.

This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (ICa-L) and repolarizing (Ito) currents. The acute effect of MeHg was evaluated on HEK293 cells expressing human ERG, Kv4.3 and KCNQ1/KCNE1 channels. Chronic MeHg treatment increased QTc and Tpeak-Tend interval duration, prolonged action potential duration and decreased amplitude of Ito and ICa-L. In addition, heterologously expressed IhKv4.3, IhERG or IhKCNQ1/KCNE1 decreased after acute exposure to MeHg at subnanomolar range. The introduction of the in vitro effects of MeHg in a computer model of human ventricular action potentials triggered early afterdepolarizations and arrhythmia. In conclusion, cardiac electrical remodeling induced by MeHg poisoning is related to the reduction of Ito and ICa-L. The acute effect of MeHg on hKv4.3; hERG and hKCNQ1/KCNE1 currents and their transposition to in silico models show an association between MeHg intoxication and acquired Long QT Syndrome in humans. MeHg can exert its high toxicity either after chronic or acute exposure to concentrations as low as picomolar.

Elevated mercury bound to serum proteins in methylmercury poisoned rats after selenium treatment.

Methylmercury is a toxic pollutant and is generated by microbial methylation of elemental or inorganic mercury in the environment. Previous study found decreased hepatic MDA levels and urinary mercury levels in methylmercury poisoned rats after sodium selenite treatment. This study further found increased mercury levels in serum samples from methylmercury poisoned rats after selenium treatment. By using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, three Hg- binding protein fractions and two Se-binding protein fractions were identified with the molecular weight of approximately 21, 40, and 75 kDa and of 40 and 75 kDa, respectively. Elevated mercury level in the 75 kDa protein fraction was found binding with both Hg and Se, which may explain the decreased urinary Hg excretion in MeHg poisoned rats after Se treatment. MALDI-TOF-MS analysis of the serum found that the 75 kDa protein fractions were albumin binding with both Hg and Se and the 21 kDa fraction was Hg- binding metallothionein.

Mercury in Hazel Bolete Leccinum griseum and soil substratum: Distribution, bioconcentration and dietary exposure.

This study aimed to examine the accumulation and distribution of total mercury (Hg) in fruiting bodies of edible wild-grown mushroom Hazel Bolete Leccinum griseum (Quél.) Singer, collected from six spatially distantly distributed places across Poland and to assess the probable dietary intake of the element by consumers. Mercury content of fungal and soil samples were determined by cold-vapour atomic absorption spectroscopy (CV-AAS) with a direct sample thermal decomposition coupled with gold wool trap of Hg and its further desorption and quantitative measurement at the wavelength of 296 nm. The median values of Hg content in caps of L. griseum collected from less-contaminated places (< 0.10 mg Hg kg(-1) dry matter in upper 0-10 cm layer of soil substratum) were from 0.23 mg kg(-1) dm to 0.43 mg kg(-1) dm. And for more contaminated topsoil (0.15 mg Hg kg(-1) dry matter), the median in caps was about 1.5 mg kg(-1) dry matter. The mushroom L. griseum has potential to accumulate Hg in fruiting bodies, while quantities of this element noted in consignments of this species originating from the forests with typical background values of Hg in topsoil are low. In the light of the published value of PTWI for Hg consumption of fruiting bodies of L. griseus emerged in forests of Poland is without health risk for consumers. Information on total mercury and methylmercury in Fungi of the genus Leccinum is also described briefly.

Associations of prenatal maternal blood mercury concentrations with early and mid-childhood blood pressure: a prospective study.

BACKGROUND: Childhood blood pressure (BP) is an important determinant of adult cardiovascular disease. Prenatal exposure to methylmercury through maternal fish consumption has been reported to increase the BP of children years later. METHODS: Mother-child pairs were enrolled from Project Viva, a prospective cohort study in Massachusetts. From second trimester maternal blood samples, we measured erythrocyte mercury concentration. Systolic BP in children, measured up to 5 times per visit in early and mid-childhood (median ages 3.2 and 7.7 years), was the primary outcome. We used mixed-effect regression models to account for variation in the number of BP measurements and to average effects over both time points. RESULTS: Among 1103 mother-child pairs, mean (SD) second trimester total erythrocyte mercury concentration was 4.0 (3.9)ng/g among mothers whose children were assessed in early childhood and 4.0 (4.0)ng/g for children assessed in mid-childhood. Mean (SD) offspring systolic BP was 92.1 (10.4)mm Hg in early childhood and 94.3 (8.4)mm Hg in mid-childhood. After adjusting for mother and infant characteristics, mean second trimester blood mercury concentration was not associated with child systolic BP (regression coefficient, 0.1mm Hg; 95% CI, -1.3 to 1.5 for quartile 4 vs. quartile 1) at either time period. Further adjusting for second trimester maternal fish consumption, as well as docosahexaenoic acid and eicosapentaenoic acid consumption, did not substantially change the estimates. CONCLUSIONS: The results of this study demonstrate an absence of association between childhood blood pressure and low-level mercury exposure typical of the general US population.

Impacts of prenatal exposures to polychlorinated biphenyls, methylmercury, and lead on intellectual ability of 42-month-old children in Japan.

BACKGROUND: The age-specific impacts of perinatal exposures to polychlorinated biphenyls (PCB), methylmercury (MeHg), and lead on child neurodevelopment remain controversial. Since we have already reported the prenatal effects of these chemicals on neurodevelopment in 3-day-old and 30-month-old children of a birth cohort, the following effects were analyzed in the 42-month-old children in the same cohort. METHODS: The Kaufman Assessment Battery for Children (K-ABC), comprised of four scales, was used to assess their intelligence and achievement. The relationships between the chemicals and K-ABC scores were analyzed using multivariate analyses. RESULTS: The median values of chemicals in cord blood of 387 children were 46.5 (5th and 95th percentiles, 16.7-115.7)ng/g-lipid for total PCB, 10.1 (4.3-22.2)ng/g for total mercury (THg), and 1.0 (0.5-1.8) µg/dL for lead. Of the highly chlorinated PCB homologs, 9 CBs was negatively correlated with the sequential and mental processing score of the K-ABC (p<0.05). There were no significant correlations between any K-ABC score and either THg or lead. The negative effect of 9 CBs remained even after adjusting for THg, lead, and other confounders. The K-ABC scores were significantly lower in the boys than in the girls, and the standardized ß of 9 CBs for the sequential and mental processing scores in multiple regression analysis was statistically significant in boys. CONCLUSIONS: These findings suggest that intellectual ability in the developmental stage may be impaired by prenatal exposures to highly chlorinated PCB homologs, especially in Japanese boys.

Neurological and Neurocognitive Impairments in Adults with a History of Prenatal Methylmercury Poisoning: Minamata Disease.

Minamata disease, which happened during the 1950s and 1960s in Minamata, Japan, is a well-known case of food poisoning caused by methylmercury-contaminated fish. Although many children were born, in the affected areas, with severe neurological signs after birth (known as congenital Minamata disease (CMD)), few studies have explored the possible effects of low-to-moderate methylmercury exposure in utero, probably at lower levels than in CMD patients, in Minamata. We, therefore, recruited 52 participants in 2020: 10 patients with known CMD; 15 moderately exposed residents; and 27 non-exposed controls. The average umbilical cord methylmercury concentrations were 1.67 parts per million (ppm) for CMD patients and 0.77 ppm for moderately exposed participants. After conducting four neuropsychological tests, we compared the functions among the groups. Compared with the non-exposed controls, both the CMD patients and moderately exposed residents had worse scores in the neuropsychological tests, although the score decline was more severe in the CMD patients. For example, even after adjusting for age and sex, the CMD patients and moderately exposed residents had 16.77 (95% CI: 13.46 to 20.08) and 4.11 (95% CI: 1.43 to 6.78) lower scores in the Montreal Cognitive Assessment, respectively, than the non-exposed controls. The present study indicates that residents of Minamata who experienced low-to-moderate prenatal methylmercury exposure also have neurological or neurocognitive impairments.

Methyl mercury exposure at Niigata, Japan: results of neurological examinations of 103 adults.

BACKGROUND: Large-scale poisonings caused by methyl mercury (MeHg) have occurred in Japan (Minamata in the 1950s and Niigata in the 1960s) and Iraq (in the 1970s). The current WHO neurological risk standard for adult exposure (hair level: 50 µg/g) was based partly on evidence from Niigata which did not consider any cases who were diagnosed later and/or exposed to low level of MeHg (hair mercury level less than 50 µg/g). METHODS: Early in the Niigata epidemic in June 1965 there were two extensive surveys. From these two surveys, we examined 103 adults with hair mercury measurement who consulted two medical institutions. We compared the prevalence and the distribution of neurological signs related to MeHg poisoning between exposure categories. RESULT: We found 48 subjects with neurological signs related to MeHg poisoning who had hair mercury concentration less than 50 µg/g. Among the neurological signs, sensory disturbance of the bilateral distal extremities was observed more frequently, followed by disequilibrium, hearing impairment, and ataxia, in groups with hair MeHg concentration both below 50 µg/g and over 50 µg/g. CONCLUSION: The present study suggests the possibility that exposure to MeHg at levels below the current WHO limits could cause neurologic signs, in particular, sensory disturbance.

Neurodevelopment of Amazonian infants: antenatal and postnatal exposure to methyl- and ethylmercury.

Neurodevelopment as Gesell development scores (GDSs) in relation to mercury exposure in infants (<6 months of age) of one urban center and two rural villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg (HHg) concentrations of infants from Itapuã (3.95 ± 1.8 ppm) were statistically (P = 0.0001) different from those of infants from Porto Velho (3.84 ± 5.5 ppm) and Bom Futuro (1.85 ± 0.9 ppm). Differences in vaccine coverage among these populations resulted in significantly higher (P = 0.0001) mean ethylmercury (EtHg) exposure in urban infants (150 µg) than in infants from either village (41.67 µg, Itapuã; 42.39 µg, Bom Futuro). There was an inverse significant (Spearman r = -0.2300; P = 0.0376) correlation between HHg and GDS for infants from Porto Velho, but not for the rural infants from Bom Futuro (Spearman r = 0.1336; P = 0.0862) and Itapuã (Spearman r = 0.1666; P = 0.5182). Logistic regression applied to variables above or below the median GDS showed that EtHg exposure (estimated probability = -0.0157; P = 0.0070) and breastfeeding score (estimated probability = -0.0066; P = 0.0536) score were significantly associated with GDS. Conclusion. In nurslings whose mothers are exposed to different levels of fish-MeHg (HHg), a higher score of neurological development at six months was negatively associated with exposure to additional TCV-EtHg. Results should be interpreted with caution because of unaccounted variables.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study.

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.

Latent effects of early-life methylmercury exposure on motor function in Drosophila.

The developmental toxicant, methylmercury (MeHg), can elicit motor deficits that last well into adulthood. Recent studies using Drosophila showed that the developing musculature is sensitive to high doses of MeHg, where a larval feeding paradigm resulted in compromised myotendinous junction (MTJ) formation during development, by a mechanism involving the NG2 homologue, kon-tiki (kon). Low-dose exposures to MeHg that do not produce muscle pathology during development, nevertheless result in impaired flight behavior later in adult life. The present study evaluated the potential for relatively low-dose exposure to produce latent adult muscle pathology and motor impairments, as assayed by climbing and flight, as well as to evaluate molecular mechanisms that may contribute to motor deficits. Wildtype larvae were fed 0, 2, 2.5, or 5 µM MeHg laden food until eclosion. The effect of 5 µM MeHg on MTJ-related gene expression during pupal development was assessed via quantitative RT-qPCR analysis. Upon eclosion, adults were transferred to standard food bottles for 4, 11, or 30 days prior to motor testing. Survivorship (%) was determined from a subset of 200 flies per treatment. Average climbing speed (cm/s) was quantified 4-days post-eclosion (PE). Flight ability was assayed 11- or 30-days PE by measuring landing height (cm) of flies dropped into an adhesive-lined vertical column. In parallel, total body mercury was measured to estimate the influence of residual MeHg at the time of motor testing. Muscle morphology was assessed using immuno-fluorescence microscopy. Exposure to 5uM MeHg significantly reduced climbing speed, and flight ability 4 and 11 - days PE, respectively. While age-related flight deficits were seen in each sex, flight deficits due to MeHg persisted to 30-day PE timepoints exclusively in males. Expression of kon was upregulated across the window of pupal development essential to establishing adult MTJ. However, experimentally restricting the induction of comparable levels of kon to muscle during the same periods did not recapitulate the flight deficits, indicating that muscle-specific induction of kon alone is not sufficient to contribute to latent flight impairments. Adult flight muscle morphology of 11-day PE flies treated with 5 µM MeHg was indistinct from controls, implying muscle structure is not grossly perturbed to impair flight. Collectively, the current data suggest that developmental exposure to 5 µM MeHg reduces flight ability in each sex at 11 day-PE and that latent deficits at 30-day PE are male-specific. It remains to be determined whether the developing MTJ of Drosophila is a sensitive target of MeHg, and whether or not kon acts in conjunction with additional MTJ factors to constitute a MeHg target.

Fish consumption in pregnancy and fetal risks of methylmercury toxicity.

QUESTION: Because I practise in a rural area with a large number of lakes, I have patients planning pregnancy who consume relatively large amounts of fish harvested by their families. What should be my advice to them? ANSWER: A recent Motherisk study has shown that fairly commonly these women's mercury levels exceed the threshold level for cognitive effects. Women should not consume excessive amounts of seafood in pregnancy (ie, no more than 2 weekly average size servings). Hair mercury level above 0.3 µg/g indicates a potentially excessive body burden.

Elemental analysis of biological specimens in air with a proton microprobe.

The unique capabilities of the proton microprobe in an atmospheric environment as a biological tool are illustrated in studies of arsenic and mercury distributions in siingle strands of hair from poisoning victims and of the distributions of several abundant elements in frozen hydrated eye and kidney specimens from rats.

Subtle consequences of methylmercury exposure: behavioral deviations in offspring of treated mothers.

Overt neurological impairment is the endpoint currently used to document a case of methylmercury poisoning. No consideration is given to possible subtle consequences. Offspring from mice exposed to methylmercury on day 7 or 9 of pregnancy were apparently unaffected during postnatal development. However, subtle behavioral differences between treated and control offspring were found when the overtly normal animals were tested in an open field and evaluated in a swimming apparatus at 1 month of age. Brain weight, protein, choline acetyltransferase, and cholinesterase were not significantly altered.

Prenatal and postnatal mercury exposure, breastfeeding and neurodevelopment during the first 5 years.

OBJECTIVE: We evaluated the association between infant hair-Hg and Gesell schedules (GS). BACKGROUND: Longitudinal assessment of prenatal and postnatal Hg exposure during the first 60 months. METHODS: We used hair-Hg as a marker of postnatal Hg exposure (inorganic and methyl-Hg from breast milk, and ethyl-Hg from thimerosal) and GS measured at 6, 36, and 60 months. RESULTS: Hair-Hg at 6 months responded to events related to Hg exposure and breastfeeding. However, most neurodevelopment delays observed at 6 months were overcome with infant growth; at 60 months 87% of children showed adequate GS (>85). Length of lactation and hair-Hg were each significantly correlated with GS, but in opposite ways: length of lactation was positive and significantly correlated with all GS at 60 months; hair-Hg concentrations were negative and significantly correlated with GS at 6 months (r=-0.333; P=0.002) and 60 months (r=-0.803; P=0.010), but not at 36 months. Multiple regression models showed that the GS outcome at 60 months depended on GS at 36 months that in turn was influenced by infants' developmental and Hg exposure variables. GS at 6 months was significantly influenced by prenatal (maternal and infant hair-Hg at birth) and postnatal Hg exposure at 6 months. CONCLUSIONS: Until there is more refined approach to recognize children sensitive to Hg exposure, and in situations of uncertainty (EtHg exposure), the neurodevelopment benefit of breastfeeding should be recommended.

Negotiating three worlds: academia, nursing science, and tribal communities.

PURPOSE: The purpose of this article is to use a cross-cultural model to guide the exploration of common issues and the dynamic interrelationships surrounding entrée to tribal communities as experienced by four nursing research teams. METHOD: Members of four research teams discuss the primary lessons learned about successful strategies and challenges encountered during their projects' early stages. RESULTS: Understanding the cultural values of relationship and reciprocity is critical to the success of research projects conducted in Native American communities. DISCUSSION: Conducting cross-cultural research involves complex negotiations among members of three entities: academia, nursing science, and tribal communities. The lessons learned in these four research projects may be instructive to investigators who have the opportunity to conduct research with tribal communities.

Mercury Involvement in Neuronal Damage and in Neurodegenerative Diseases.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis are characterized by a chronic and selective process of neuronal cell death. Although the causes of neurodegenerative diseases remain still unknown, it is now a well-established idea that more factors, such as genetic, endogenous, and environmental, are involved. Among environmental causes, the accumulation of mercury, a heavy metal considered a toxic agent, was largely studied as a probable factor involved in neurodegenerative disease course. Mercury exists in three main forms: elemental mercury, inorganic mercury, and organic mercury (methylmercury and ethylmercury). Sources of elemental mercury can be natural (volcanic emission) or anthropogenic (coal-fired electric utilities, waste combustion, hazardous-waste incinerators, and gold extraction). Moreover, mercury is still used as an antiseptic, as a medical preservative, and as a fungicide. Dental amalgam can emit mercury vapor. Mercury vapor, being highly volatile and lipid soluble, can cross the blood-brain barrier and the lipid cell membranes and can be accumulated into the cells in its inorganic forms. Also, methylmercury can pass through blood-brain and placental barriers, causing serious damage in the central nervous system. This review describes the toxic effects of mercury in cell cultures, in animal models, and in patients with neurodegenerative diseases. In vitro experiments showed that mercury exposure was principally involved in oxidative stress and apoptotic processes. Moreover, motor and cognitive impairment and neural loss have been confirmed in various studies performed in animal models. Finally, observational studies on patients with neurodegenerative diseases showed discordant data about a possible mercury involvement.

Review of food policy and consumer issues of mercury in fish.

Public health messages regarding seafood consumption are confounded by long standing dietary advice promoting the healthfulness of consuming fish and recent warnings concerning dangerous mercury levels in specified fish. The warnings vary by federal agency and are directed to vulnerable subpopulations, notably women of childbearing age, pregnant women, nursing mothers and young children. The issue of mercury in fish has received considerable media coverage, attention from consumer organizations and public policy review. The net result is an area of seemingly contradictory advice directed to consumers and health professionals on the type and quantity of fish safe to consume. This message that fish is nutritious and healthy is particularly understood by educated and affluent subpopulations who can afford a variety of fish in their diet. This review addresses the contradictory rhetoric and reviews the state and federal agency policy positions. It considers the arguments for and against disclosing mercury-related information and its anticipated impact on the extended health benefits of fish consumption versus the risk to vulnerable subpopulations. The issue of balancing and targeting healthy messages and dietary warnings on fish is important because within the U.S. childbearing population, it is conservatively estimated that 250,000 women may be exposing their fetuses to higher levels of methylmercury than is in federal public health guidelines; two million more may not be consuming enough low-mercury fish.

Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians.

BACKGROUND: In 2005, 84% of Wayana Amerindians living in the upper marshes of the Maroni River in French Guiana presented a hair mercury concentration exceeding the limit set up by the World Health Organization (10 microg/g). To determine whether this mercurial contamination was harmful, mice have been fed diets prepared by incorporation of mercury-polluted fish from French Guiana. METHODS: Four diets containing 0, 0.1, 1, and 7.5% fish flesh, representing 0, 5, 62, and 520 ng methylmercury per g, respectively, were given to four groups of mice for a month. The lowest fish regimen led to a mercurial contamination pressure of 1 ng mercury per day per g of body weight, which is precisely that affecting the Wayana Amerindians. RESULTS: The expression of several genes was modified with mercury intoxication in liver, kidneys, and hippocampus, even at the lowest tested fish regimen. A net genetic response could be observed for mercury concentrations accumulated within tissues as weak as 0.15 ppm in the liver, 1.4 ppm in the kidneys, and 0.4 ppm in the hippocampus. This last value is in the range of the mercury concentrations found in the brains of chronically exposed patients in the Minamata region or in brains from heavy fish consumers. Mitochondrial respiratory rates showed a 35-40% decrease in respiration for the three contaminated mice groups. In the muscles of mice fed the lightest fish-containing diet, cytochrome c oxidase activity was decreased to 45% of that of the control muscles. When mice behavior was assessed in a cross maze, those fed the lowest and mid-level fish-containing diets developed higher anxiety state behaviors compared to mice fed with control diet. CONCLUSION: We conclude that a vegetarian diet containing as little as 0.1% of mercury-contaminated fish is able to trigger in mice, after only one month of exposure, disorders presenting all the hallmarks of mercurial contamination.