Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome.

International audienceBACKGROUND: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized. METHODS: Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. RESULTS: The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. CONCLUSIONS: Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism

Alcool et système circadien

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Effets de l'hypoxie modérée sur le système circadien humain (simulation de vols de longue durée)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

The effects of extremely low-frequency magnetic fields on melatonin and cortisol, two marker rhythms of the circadian system

International audienceIn the past 30 years the concern that daily exposure to extremely low-frequency magnetic fields (ELF-EMF) (1 to 300 Hz) might be harmful to human health (cancer, neurobehavioral disturbances, etc) has been the object of debate, and has become a public health concern. This has resulted in the classification of ELF-EMF into category 2B, ie, agents that are 'possibly carcinogenic to humans' by the International Agency for Research on Cancer. Since melatonin, a neurohormone secreted by the pineal gland, has been shown to possess oncostatic properties, a 'melatonin hypothesis' has been raised, stating that exposure to EMF might decrease melatonin production and therefore might promote the development of breast cancer in humans. Data from the literature reviewed here are contradictory. In addition, we have demonstrated a lack of effect of ELF-EMF on melatonin secretion in humans exposed to EMF (up to 20 years' exposure) which rebuts the melatonin hypothesis. Currently, the debate concerns the effects of ELF-EMF on the risk of childhood leukemia in children chronically exposed to more than 0.4 uT. Further research is thus needed to obtain more definite answers regarding the potential deleterious effects of ELF-EMF

Acute exposure to 50-Hz magnetic fields increases interleukin-6 in young healthy men

International audienceSome epidemiologic studies have suggested that extremely low frequency magnetic fields might affect human health and, in particular, that the incidence of certain types of cancer might increase among individuals living or working in environments exposed to such fields. This study is part of a broad study we conducted in humans. The study presented here was designed to look for possible effects of acute exposure to 50-Hz magnetic fields (10 mu T) on the interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), and the interleukin-2 receptor (IL-2R) production. Thirty-two young men (20-30 years old) were divided into two groups (sham-exposed or control group and exposed group) of 16 subjects each. All subjects participated in two 24-h experiments to evaluate the effects of both continuous and intermittent (1 h "off" and 1 h "on" with the field switched "on" and "off" every 15 s) exposure to linearly polarized magnetic fields. The subjects were exposed to the magnetic field from 2300 to 0800 while recumbent. Blood samples were collected during each session at 11:00, 17:00, 22:00, 01:00, 04:00, 06:00, and 08:00. Results showed that exposure to 50-Hz magnetic fields (10 mu T) significantly increases IL-6 when subjects were exposed to an intermittent magnetic field. However, no effect has been observed on interleukin IL-1 beta, IL-2, IL-1RA, and IL-2R

Assessment of cortisol secretory pattern in workers chronically exposed to ELF-EMF generated by high voltage transmission lines and substations

International audienceWe investigated the effects of extremely-low frequency electromagnetic fields (ELF-EMFs; 50 Hz) on the secretion of cortisol in 14 men (mean age = 38.0 +/- 0.9 years) working in extra-high voltage (EHV) substations. The workers dwelt in houses that were close to substations and high-voltage lines. Thus, they had long histories (1-20 years) of long-yerm exposure to ELF-EMFs. Magnetic field strength was recorded using Emdex dosimeters worn by the volunteers day and night for seven days; the one-week geometric mean ranged from 0.1 to 2.6 mu T. Blood samples were taken hourly from 20:00 to 08:00 the next morning. Cortisol concentrations and patterns were compared to age-matched, unexposed control subjects whose exposure level was ten times lower. The comparison of the control group (n = 15) and the groups exposed to fields of 0.1-0.3 mu T (n = 5) and > 0.3 mu T (n = 9), respectively, revealed a significant effect of field intensity on the cortisol secretory pattern. This study strongly suggests that chronic exposure to ELF-EMFs alters the peak-time serum cortisol levels. Studies are required on the effect of this disruption in high-risk populations such as children, elderly people, and patients with cancer