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Aluminum and Glyphosate Can Synergisti-cally Induce Pineal Gland Pathology: Con-nection to Gut Dysbiosis and Neurological Disease
Abstract and Figures
Many neurological diseases, including autism, depression, dementia, anxiety disorder and Par-kinson's disease, are associated with abnormal sleep patterns, which are directly linked to pineal gland dysfunction. The pineal gland is highly susceptible to environmental toxicants. Two pervasive substances in modern industrialized nations are aluminum and glyphosate, the active ingredient in the herbicide, Roundup ®. In this paper, we show how these two toxicants work synergis-tically to induce neurological damage. Glyphosate disrupts gut bacteria, leading to an overgrowth of Clostridium difficile. Its toxic product, p-cresol, is linked to autism in both human and mouse models. p-Cresol enhances uptake of aluminum via transferrin. Anemia, a result of both aluminum disruption of heme and impaired heme synthesis by glyphosate, leads to hypoxia, which induces increased pineal gland transferrin synthesis. Premature birth is associated with hypoxic stress and with substantial increased risk to the subsequent development of autism, linking hypoxia to autism. Glyphosate chelates aluminum, allowing ingested aluminum to bypass the gut barrier. This leads to anemia-induced hypoxia, promoting neurotoxicity and damaging the pineal gland. Both glyphosate and aluminum disrupt cytochrome P450 enzymes, which are involved in mela-tonin metabolism. Furthermore, melatonin is derived from tryptophan, whose synthesis in plants and microbes is blocked by glyphosate. We also demonstrate a plausible role for vitamin D3 dys-biosis in impaired gut function and impaired serotonin synthesis. This paper proposes that impaired sulfate supply to the brain mediates the damage induced by the synergistic action of aluminum and glyphosate on the pineal gland and related midbrain nuclei.
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... The edible as well as non-edible part of plants is the common source of these compounds (Heim, Tagliaferro & Bobilya, 2002). Earlier studies suggested the inherent capacity of plants gets activated upon herbicide exposure to defend against the generated consequences through their defense machinery (Seneff, Swanson & Li, 2015). In our study increased antioxidant activity in lentil seedlings upon imazethpyr application indicates the activation of these defense mechanisms through enhanced activity of PAL and POD and increased synthesis of phenolic acid and flavonoids. ...
... Herbicides that enhance phenol accumulation in plants, also lead to consequent stimulation of antioxidant activity (Seneff, Swanson & Li, 2015). Increased antioxidant activity in lentil seedlings in the present study at higher doses suggests the potential role of phenolic compounds in overcoming the herbicidal effects. ...
The imidazolinone group of herbicides generally work for controlling weeds by limiting the synthesis of the aceto-hydroxy-acid enzyme, which is linked to the biosynthesis of branched-chain amino acids in plant cells. The herbicide imazethapyr is from the class and the active ingredient of this herbicide is the same as other herbicides Contour, Hammer, Overtop, Passport, Pivot, Pursuit, Pursuit Plus, and Resolve. It is commonly used for controlling weeds in soybeans, alfalfa hay, corn, rice, peanuts, etc. Generally, the herbicide imazethapyr is safe and non-toxic for target crops and environmentally friendly when it is used at low concentration levels. Even though crops are extremely susceptible to herbicide treatment at the seedling stage, there have been no observations of its higher dose on lentils (Lens culinaris Medik.) at that stage. The current study reports the consequence of imazethapyr treatment on phenolic acid and flavonoid contents along with the antioxidant activity of the phenolic extract. Imazethapyr treatment significantly increased the activities of several antioxidant enzymes, including phenylalanine ammonia lyase (PAL), phenol oxidase (POD), glutathione reductase (GR), and glutathione-s-transferase (GST), in lentil seedlings at doses of 0 RFD, 0.5 RFD, 1 RFD, 1.25 RFD, 1.5 RFD, and 2 RFD. Application of imazethapyr resulted in the 3.2 to 26.31 and 4.57–27.85% increase in mean phenolic acid and flavonoid content, respectively, over control. However, the consequent fold increase in mean antioxidant activity under 2, 2- diphenylpicrylhdrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay system was in the range of 1.17–1.85 and 1.47–2.03%. Mean PAL and POD activities increased by 1.63 to 3.66 and 1.71 to 3.35-fold, respectively, in agreement with the rise in phenolic compounds, indicating that these enzyme’s activities were modulated in response to herbicide treatment. Following herbicide treatments, the mean thiol content also increased significantly in corroboration with the enhancement in GR activity in a dose-dependent approach. A similar increase in GST activity was also observed with increasing herbicide dose.
... Different studies indicated that pineal gland calcification was significantly associated with age, sex, low altitude, low sunlight exposure, ethnicity, light, cell phone, fluoride intake, nutrition, and neurodegenerative diseases [7]. A modern lifestyle like using electromagnetic field (EMF)-emitting material such as cell phones and audio/video players; using fluoride in mouthwash, toothpaste, and tab water; and using herbicides were also considered as the critical risk factors for pineal gland calcification [12,28,29]. The prevalence of pineal gland calcification was highest in older age individuals compared with those of young and also highest among obese. ...
... In this study, there is a high prevalence of pineal gland calcification detected by CT scan and most studies showed that males have a high prevalence of pineal gland calicifcation [2][3][4][5][6][7]. Even though there is no clear justification for this variation of pineal gland calcification by sex of individuals, many other studies link such differences to the effect of melatonin on gonadotropins [28][29][30]. As a limitation, most of the studies lack clinical and laboratory data on the function of the pineal gland, making it difficult to extrapolate these findings to neurodegenerative changes in a clinically relevant way. ...
Background
Pineal gland calcification is the formation of corpora arenacea predominantly composed of calcium and phosphorus. It plays an important role in regulating the light/dark circadian changes to synchronize their daily physiological activities like feeding, metabolism, reproduction, and sleep through the secretion of melatonin. Therefore, this study aimed to assess the pooled prevalence of pineal gland calcification.
Methods
A systematic review was done using published research articles from different electronic databases. Cross-sectional studies were included for systematic review and only studies conducted on the human population were included for quantitative analysis. Published articles were selected by assessing the title and abstract for relevance to the review objectives. Finally, the full text was retrieved for further assessment.
Results
The pooled prevalence of pineal gland calcification was 61.65% [95% CI: 52.81, 70.49], with a heterogeneity of I² = 97.7%, P ≤ 0.001. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
Conclusion
The pooled prevalence of pineal gland calcification was higher compared with reports from previous studies. Different studies reported pineal gland calcification was most prevalent in the adult population compared with the pediatric age groups. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
... Based on the impacts on human health as early as the 90s of the last century, investigations of research centers of excellence in the northern hemisphere has proved the highly harmful effects on human health of the herbicide 2-4D used in the Vietnam War, particularly its carcinogenic effect, the damage to the nervous system, and deformations in descendants of the population exposed to its use (Fogel, 2001). In recent years, new research has focused on the growing neurological damage caused by agrochemicals and particularly on the effects of glyphosate on prenatal health (Bellinger et al, 2016;Falnoga et al., 2000;Mesnage et al., 2013;Mesnage et al., 2014;Nevison, 2014;Seneff et al., 2015;Seralini et al., 2014;Swanson et al., 2014). ...
... us, Seneff et al. (2015) present evidence of the synergistic incidence of glyphosate and aluminum in pathologies of the pineal gland, related to intestinal dysfunctions and neurological diseases. Various neurological disorders including autism, depression, dementia, anxiety disorders, Parkinson's disease are associated with abnormal sleep patterns directly linked to dysfunctions of the pineal gland; various neurological disorders including autism, depression, dementia, anxiety disorders, Parkinson's disease are associated with abnormal sleep patterns directly related to dysfunctions of the pineal gland; in turn, this gland is highly susceptible to two substances with a strong presence in the industrialized nations which are aluminum and glyphosate; the latter is an active ingredient in the Round Up herbicide. ...
Según un informe de Monsanto, Paraguay es el país más transgénico considerando la superficie cultivada con OGM. Esto supone un desarrollo notable de las fuerzas productivas que alteran profundamente las relaciones de producción con la aparición de nuevos actores y la desaparición de otros. El desarrollo de nuevas tecnologías también tiene consecuencias en la salud humana, en la intensa contaminación ambiental y en la deforestación de ecosistemas frágiles. En lo que va de este siglo, las grandes corporaciones biotecnológicas que promueven el régimen agroalimentario globalizado emplean tecnologías adecuadas para los cultivos transgénicos, siendo el RR más emblemático del Monsanto que requiere una economía de escala asociada con la concentración de la tierra y su acumulación y utiliza pesticidas en cantidades crecientes, una característica que lo hace autodestructivo como una nueva forma de acumulación. Mientras que los actores dominantes se convierten en representantes de grandes corporaciones, los empresarios brasileños de agronegocios, basados en la soja, dependen de quienes controlan la tecnología y los mercados. La reestructuración agraria también implica la instalación y operación de grandes corporaciones brasileñas que controlan la industria de la carne.
... Existe evidencia suficiente de los límites sociales del agronegocio sojero ya que está comprobada su incidencia en el aumento notable de afecciones neurológicas, así como sus efectos teratogénicos y cancerígenos. A pesar de los registros insuficientes, el Paraguay presenta altas y crecientes tasas de mortalidad por cáncer, así como preocupantes tasas de crecimiento de la mortalidad infantil por deformaciones que escalan de año en año, de la mortandad infantil por deformaciones (Swanson et al, 2014;Seneff et al, 2015;Mesnage, 2014;Bellinger et al, 2016;Fogel, 2018). ...
En el trabajo se analizan las modalidades e impactos de la expansión del capital agrario en el Paraguay, respondiendo a la movilidad del mercado global de capitales. Esas formas de intervención están asociadas al extractivismo agrario que operan como economías de enclave; éstas al basarse en la explotación desregulada de recursos naturales responden a ciclos de constitución, expansión y decadencia. La caracterización de las formas de extractivismo que se dieron y se siguen desarrollando permite un análisis comparativo de sus impactos. Las conclusiones destacan los costos sociales y ambientales del capital agrario orientado al extractivismo, con escasos vínculos con el mercado interno, y tiene implicancias para las políticas públicas y para el debate sobre el desarrollo. En el artículo se explotan datos secundarios de tipo estadístico, resultados de investigaciones publicadas y entrevistas semiestructuradas.
... However, there is less awareness of adult ADHD as a condition, but a systematic study determined that 2.58% of the population worldwide continues to have symptoms of ADHD even after they age out of a childhood diagnosis, and, overall, 6.76% of the global adult population suffers from symptomatic adult ADHD [41]. A study of the trends over time in the United States of ADHD prevalence (according to US Centers for Disease Control and Prevention 6 (CDC) data) showed a rising trend over time from 1990 to 2010, which correlated very strongly with the rising use of glyphosate on corn and soy crops (R = 0.9466, p ≤ 0.000036) [42]. While correlation does not necessarily mean causation, there is an increasing number of peer-reviewed publications showing evidence that glyphosate causes specific pathologies that are linked with ADHD. ...
Brazil is the world leader in pesticide consumption, and its indiscriminate use puts farmers’ health at risk. The CYP2C9 gene stands out for encoding the CYP2C9 enzyme, which metabolizes several endogenous substrates and specific xenobiotics, especially pesticides. Our goal is to study the risk of pesticide use, espe-cially the herbicide glyphosate, in the development of diseases and the association with two CYP2C9 poly-morphisms, in farmers living in the southern region of Espírito Santo state, Brazil. The allelic frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was determined in blood samples from individuals exposed or not to pesticides using real-time PCR. 304 blood samples were analyzed, dividing CYP2C9 genotypes into three metabolization classes: normal, intermediate, and slow. Our results show that normal metabolizers are more vulnerable to diseases such as blood pressure changes and cardiovascular and kidney problems, while in-termediate metabolizers show an association with attention deficit disorder and miscarriages, suggesting that farmers in the studied region developed symptoms correlated to the CYP2C9 genotype they have. This work is pioneering in associating specific genetic variations and health risks with pesticide exposure, em-phasizing the importance of personalized medicine and stricter regulation of pesticide use for public health and occupational safety.
... The work is happening at a slow pace. 46 Heavy metals are components of the jab 47 . Again, this explains the complex structure we have seen images of in previous chapters. ...
This book explains and evidences the toxic content of the COVID vaccines, causing, among others, excess mortality. It acknowledges the cover up of official entities and put the total picture into a context of society we are living in. This book may change your worldview and belief system.
... Brazilian Journal of Development, Curitiba, v.9, n.1, p. 1104-1124, jan., 2023 Aparte de la Declaración de la IARC, hay evidencia abrumadora de la relación entre los melanomas malignos y la exposición al glifosato; en el caso de Paraguay, la tasa de mortalidad por cáncer aumenta cada año (gráfico N° 1) de 60,9 por 100.000 habitantes a 66,2 100.000 en 2020. En el 2007 la tasa en cuestión fue de 54,3 muertes por 100.000 habitantes.Numerosos estudios se focalizan en daños neurológicos que van aumentando y que son causadas por agroquímicos, particularmente se investiga sobre los efectos del glifosato en la salud prenatalSeneff et al (2015) presentan evidencias de la incidencia sinérgica del glifosato y el aluminio en patologías de la glándula pineal, un pequeño órgano del cerebro que produce melatonina, que están relacionadas con disfunciones intestinales y alteraciones neurológicas. Disfunciones de la glándula pineal están asociadas con desórdenes de la ansiedad, enfermedad de Parkinson y pautas anormales de sueño.Gráfico Nº 1 Tasa de mortalidad por tumor maligno Fuente: Dirección General de Información Estratégica en Salud (2022) Esta glándula es altamente sensible a dos sustancias con mucha presencia en las naciones industrializadas que son el aluminio y el glifosato, un ingrediente activo del herbicida Roundup; conforme lo señalan estos autores el glifosato interfiere en el funcionamiento intestinal afectando el metabolismo de sustancias necesarias para el cerebro. ...
En el artículo se caracteriza y analiza efectos colaterales del régimen agroalimentario neoliberal poniendo el foco en la producción de soja transgénica considerada como economía de enclave. Se destaca el control del mercado por grandes corporaciones oligopólicas y la producción directa encarada por sojeros brasileños. Los daños ocasionados están referidos a la salud pública, al medio ambiente, a la caída en la producción de alimentos a nivel nacional y al control de los recursos naturales y de tierras de comunidades indígenas y campesinas. Se utilizan datos estadísticas de los últimos 20 años y resultados de investigaciones en ciencias biomédicas.
... Segundo os estudos, a combinação entre alumínio e glifosato, especificamente, interrompe o funcionamento da glândula pineal, induzindo danos neurológicos, inclusive com evidências de relação com o autismo. Além disso, o glifosato interfere em caminhos importantes da absorção de aminoácidos no sistema gastrointestinal, destruindo a flora intestinal, que é essencial à saúde e responsável pelo sistema imunológico, com efeitos nefastos e envelhecimento precoce 25 . ...
This work thematizes the problem of socio-sanitary and environmental consequences of the vicious circle that links human rights violations, food insecurity, and institutionalized intoxication, mainly in relation to the effects on mental health resulting from environmental contaminants and pesticides. The predatory model of post-industrial capitalism was born linked to central factors, such as: chemical-dependent agriculture, social medicalization, and nutritional transition, associated with the perverse commodification of natural resources. The expansion of large-scale monocultures using pesticides and other environmental contaminants, the expansion of the pharmaceutical industry and medical technology, and the expansion of the industrial additivated food model are consequences associated with these interconnected factors. In addition, this process is stimulated and reproduced in an institutionalized and legalized way and has been producing multiple human rights violations and the deepening of various forms of intoxication and illness: this model can be called the ‘paradigm of the chemicalization of life’.
KEYWORDS
Mental health; Agrochemicals; Right to health; Environmental health; Food security; Human rights
The use of herbicides such as glyphosate in the agricultural sector enables agricultural intensification and thus satisfies the demand for agricultural products on the market. Glyphosate is widely used in agriculture as a herbicide for weeding fields. However, its use has a major drawback that calls into question its many advantages. After use, its toxic residues and metabolites end up in groundwater, which is an important source of drinking water for the population. Adsorption is the most suitable technique for recovering these toxic residues before the water is consumed. Based on Density Functional Theory, implemented in the VASP simulation code, we studied the ability of illite to adsorb glyphosate. The absorbent properties, the abundance of illite throughout the world, particularly in Benin, and the fact that it is free from toxic products were the criteria that guide us in the of illite clay for our work. Our work revealed that the process of adsorption of glyphosate on the illite surface is exothermic. This process does not present any risk of release of toxic by-products on five of the six studied sites. The illite clay can then be used to design water depollution filters to decrease medical as well as financial burden.
The herbicide Glyphosate (GLY), or N-(phosphonomethyl) glycine was synthesized in 1950 and applied to control weeds in agricultural production. For a long time, it was believed that it was an inert compound, but many studies have instead demonstrated over the years the dangers of GLY to the ecosystem and human health. Among the best-known effects, it is known that GLY interferes with the metabolic pathways of plants and the main groups of microorganisms, negatively influencing their growth. GLY interferes with the metabolic pathways of plants and major groups of microorganisms negatively affecting their growth. The extensive GLY application on fields results in a "slow death" of plants through the minor resistance to root pathogens and in increasing pollution of freshwaters and soils. Unfortunately, however, unlike the old beliefs, GLY can reach non-target destinations, in this regard, ecological studies and environmental epidemiology are of significant interest. In this review, we focus on the effects of acute and chronic exposure to GLY on the health of plants, animals, and humans from a One Health perspective. GLY has been linked to neurological and endocrine issues in both humans and animals, and behavioral modification on specific bioindicators, but the knowledge about the ratio cause-and-effect still needs to be better understood and elucidated. Environmental GLY residues analysis and policy acts will both require new criteria to protect environmental and human health.
To investigate the role of 5-HT in the development of the somatosensory cortex, this amine was depleted in newborn (P-0) rats with a single subcutaneous injection of the toxin 5,7-dihydroxytryptamine (5,7-DHT) and thalamocortical organization was assayed by application of the carbocyanine dye Di-I to the thalamocortical radiations or ventrobasal thalamus, or by staining cortical sections for AChE or cytochrome oxidase (CO). High-performance liquid chromatographic analysis of cortices from animals killed on P-6 or P > 60 demonstrated that 5,7-DHT treatment resulted in 85.04 +/- 12.6% and 72.5 +/- 1.5% reductions in cortical 5-HT, respectively. Alternate cortices from the brains of animals killed on P-6 processed for 5-HT immunoreactivity demonstrated a complete absence of the vibrissa-related pattern of immunoreactivity and only a small number of coarse immunoreactive axons. The 85% depletion of 5-HT did not alter the somatotopic organization of thalamocortical afferents in animals killed on P-6 or P > 60, but it did cause 30.5 +/- 7.3% and 19.1 +/- 3.7% reductions in the cross- sectional areas of the patches of thalamocortical afferents corresponding to the long mystacial vibrissae (p < 0.05). These reductions were not associated with significant reductions in either brain or cortical weight or with decreases in the dimensions of the thalamic representation of the vibrissa follicles. These results indicate that 5-HT plays a significant role in the development of the thalamic innervation of the primary somatosensory cortex.
Glyphosate residues in different organs and tissues as lungs, liver, kidney, brain, gut wall and heart of malformed euthanized one-day-old Danish piglets (N= 38) were tested using ELISA. All organs or tissues had glyphosate in different concentrations. The highest concentrations were seen in the lungs (Range 0.4-80 µg/ml) and hearts (Range 0.15-80 µg/ml). The lowest concentrations were detected in muscles (4.4-6.4 µg/g). The detection of such glyphosate concentrations in these malformed piglets could be an allusion to the cause of these congenital anomalies. Further investigations are urgently needed to prove or exclude the role of glyphosate in malformations in piglets and other animals.
A huge increase in the incidence and prevalence of chronic diseases has been reported in the United
States (US) over the last 20 years. Similar increases have been seen globally. The herbicide
glyphosate was introduced in 1974 and its use is accelerating with the advent of herbicide-tolerant
genetically engineered (GE) crops. Evidence is mounting that glyphosate interferes with many
metabolic processes in plants and animals and glyphosate residues have been detected in both.
Glyphosate disrupts the endocrine system and the balance of gut bacteria, it damages DNA and is a
driver of mutations that lead to cancer.
In the present study, US government databases were searched for GE crop data, glyphosate
application data and disease epidemiological data. Correlation analyses were then performed on a
total of 22 diseases in these time-series data sets. The Pearson correlation coefficients are highly
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significant (< 10 ) between glyphosate applications and hypertension (R = 0.923), stroke (R = 0.925),
diabetes prevalence (R = 0.971), diabetes incidence (R = 0.935), obesity (R = 0.962), lipoprotein
metabolism disorder (R = 0.973), Alzheimer’s (R = 0.917), senile dementia (R = 0.994), Parkinson's (R
= 0.875), multiple sclerosis (R = 0.828), autism (R = 0.989), inflammatory bowel disease (R = 0.938),
intestinal infections (R = 0.974), end stage renal disease (R = 0.975), acute kidney failure (R = 0.978),
cancers of the thyroid (R = 0.988), liver (R = 0.960), bladder (R = 0.981), pancreas (R = 0.918), kidney
(R = 0.973) and myeloid leukaemia (R = 0.878).
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The Pearson correlation coefficients are highly significant (< 10 ) between the percentage of GE corn
and soy planted in the US and hypertension (R = 0.961), stroke (R = 0.983), diabetes prevalence (R =
0.983), diabetes incidence (R = 0.955), obesity (R = 0.962), lipoprotein metabolism disorder (R =
0.955), Alzheimer’s (R = 0.937), Parkinson's (R = 0.952), multiple sclerosis (R = 0.876), hepatitis C (R
= 0.946), end stage renal disease (R = 0.958), acute kidney failure (R = 0.967), cancers of the thyroid
(R = 0.938), liver (R = 0.911), bladder (R = 0.945), pancreas (R = 0.841), kidney (R = 0.940) and
myeloid leukaemia (R = 0.889). The significance and strength of the correlations show that the effects
of glyphosate and GE crops on human health should be further investigated.
Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the Collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.
Although no single experimental paradigm has, as yet, recapitulated all of the neuropathological and neurochemical processes of Alzheimer's disease, the use of aluminum as an experimental neurotoxicant can, at one time or another, give rise to virtually every process observed to be aberrant in Alzheimer's disease. Variations in the speciation of aluminum utilized, the age of the host animal, the in vitro conditions, the duration of the aluminum exposure, or the analytical methods utilized all contribute to this observation. Hence, as will be reviewed in this chapter, although the aetiology of Alzheimer's disease remains unknown, paradigms of aluminum toxicity remain potent tools in understanding this process.
The term "neurosteroids" applies to those steroids that are both synthesized in the nervous system, either de novo from cholesterol or from steroid hormone precursors, and that accumulate in the nervous system to levels at least in part independent of steroidogenic gland secretion rates. Glial cells play a major role in neurosteroid formation and metabolism. Several neurosteroids are involved in either auto- or paracrine mechanisms implicating both regulation of target gene expression and effects on membrane receptors (including those of neurotransmitters). The neuromodulatory role of neurosteroids in regulating the estrus cycle and pregnancy, stress, memory, developmental and aging processes awaits further investigation.
Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30–80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure.
Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls.
There are no consistent effects of first-generation antipsychotics on measuresof sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine and ziprasidone, and an increase in SWS documented for olanzapine and ziprasidone in healthy subjects.
The treatment of schizophrenic patients with first-generation antipsychotics is consistently associated with an increase in TST and sleep efficiency, and mostly an increase in REM latency, whereas the influence on specific sleep stages is more variable. On the other hand, withdrawal of such treatment is followed by a change in sleep structure mainly in the opposite direction, indicating a deterioration of sleep quality. On the background of the rather inconsistent effects of first-generation antipsychotics observed in healthy subjects, it appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology. In contrast, the available data concerning second-generation antipsychotics (clozapine, olanzapine, risperidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity in patients and healthy subjects, with an increase in TST and sleep efficiency or a decrease in wakefulness. Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients. Possibly, the effects of second-generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms.
Specific sleep disorders, such as RLS, sleep-related breathing disorders, night-eating syndrome, somnambulism and rhythm disorders have been described as possible adverse effects of antipsychotics and should be considered in the differential diagnosis of disturbed or unrestful sleep in this population.
Sleep–wake problems are frequent, although unrecognized, complications of amyotrophic lateral sclerosis (ALS). Sleep disorders such as insomnia, sleep-disordered breathing and restless legs syndrome have all been reported in patients with ALS, despite the limited number of studies and the small populations investigated so far. Sleep disturbances gradually worsen with disease progression, suggesting a relationship between the severity of disease and the neurodegenerative process. However, poor sleep can also be a consequence of several disturbances such as anxiety, depression, pain, choking, sialorrhea, fasciculations, cramps, nocturia and the inability to get comfortable and move freely in bed. Sleep disorders may have many reflections on patients with ALS, including excessive daytime somnolence, fatigue, impaired cognition, reduced quality of life and survival. This article reviews the recent literature on sleep–wake problems in patients with ALS, focusing on the implications for patient management.
Between September 1972 and January 1976 an outbreak of dialysis dementia affected 20 patients maintained by long-term hemodialysis. The clinical picture was characterized by an insidious onset of altered behaviour, dementia, speech disturbance, myoclonus, and convulsions. Nineteen patients died, but one patient has survived for 16 months. It was later established that in June 1972 the city had altered its method of water purification and that this resulted in higher water aluminum levels. The temporal relation between periods of high water-aluminum content and the appearance of new cases supports the view that aluminum may play a role in the causation of dialysis dementia.
• Polysomnographic abnormalities in schizophrenia are not well characterized and their associations with schizophrenic symptomatology have not been adequately assessed. To address these issues, we recorded electroencephalographic sleep in 20 drug-naive schizophrenics, 20 drugfree but previously medicated schizophrenics, and 15 normal controls. Drug-naive and previously medicated patients had significantly greater impairment of sleep continuity and shorter rapid eye movement latency when compared with controls. In the previously medicated group, findings were significantly influenced by duration of drugfree status. Rapid eye movement latency was inversely correlated with the severity of negative symptoms (r= -$.52) but was unrelated to depressive symptoms. Slow-wave sleep did not differ between schizophrenic patients and normal controls and was unrelated to any clinical parameter. Mechanisms underlying the observed associations between rapid eye movement sleep abnormalities and negative symptoms in the acute phase of schizophrenic illness need to be explored.