RESUMO
The assumed dominance of chloride (Cl-) in terrestrial ecosystems is challenged by observations of extensive formation of organically bound Cl (Clorg), resulting in large soil Cl storage and internal cycling. Yet, little is known about the spatial distribution of Cl in ecosystems. We quantified patterns of Cl distribution in different habitats along a boreal hillslope moisture gradient ranging from relatively dry upland coniferous forests to wet discharge areas dominated by alder. We confirmed that dry habitats are important for Cl storage but found that Cl pools tended to be larger in moist and wet habitats. The storage of Clorg was less important in wet habitats, suggesting a shift in the balance between soil chlorination and dechlorination rates. Cl concentrations in the herb layer vegetation were high in wet and moist sites attributed to a shift in plant species composition, indicating plant community-dependent ecosystem Cl cycling. Mass-balance calculations showed that internal Cl cycling increased overall ecosystem Cl residence times at all sites and that plant uptake rates of Cl- were particularly high at wet sites. Our results indicate that habitat characteristics including plant communities and hydrology are key for understanding Cl cycling in the environment.
Assuntos
Ecossistema , Solo , Cloro/análise , Áreas Alagadas , Cloretos , Florestas , PlantasRESUMO
A methodology for addressing the biosphere in safety assessments for solid radioactive waste disposal was developed through theme 1 of the IAEA coordinated research project on BIOsphere Modelling and ASSessment (BIOMASS) that ran from 1996 to 2001. This methodology provided guidance on how the biosphere can be addressed in safety assessments for disposal of solid radioactive waste. Since the methodology was developed, it has proven useful and has been widely referenced in assessments in a diversity of contexts encompassing both near-surface and deep geological disposal of solid radioactive waste. The principles that could be adopted for defining potentially exposed groups (PEGs) were an important aspect in the original BIOMASS methodology as the endpoint of an assessment usually includes the evaluation of individual dose or risk to human health. Identification of PEGs and definition of their characteristics are usually made to be consistent with the biosphere system description being developed, acknowledging that due to inherent uncertainties in projecting future human behaviour, the biosphere models adopted for assessing safety of a disposal system can only be illustrative. Since the publication of the original BIOMASS methodology, consideration has been extended to include potentially exposed populations of biota (PEPs), in the context of dose assessment and protection of the environment. Considering the need for the development of transfer pathways from a source term to an end point (for either PEGs or PEPs), the exposure modes that may occur and those to be assessed quantitatively should be identified. Within an expert working group (WG6) of the second phase of the IAEA coordinated project Modelling and Data for Radiological Impact Assessments (MODARIA II), the experience of participating organisations has been collected on topics associated with the definition of PEGs and PEPs using a questionnaire. The objective of the questionnaire was to review the current status and on-going discussions on the handling of issues related to definitions of PEGs and PEPs as an input to the development of biosphere models for assessing radiological impacts on human health and the environment. The answers received to the questionnaire provided a clear overview of the progress that has been made since the original BIOMASS methodology was published, together with the lessons learned from the application of that methodology in the development of safety cases. This paper summarises the questionnaire responses in five subject areas: (1) environment of the PEGs and its evolution; (2) linking the choice of PEGs to these environments; (3) food habits and consumption rates; (4) populations of non-human biota (PEPs) and (5) national and international regulations and guidance. We illustrate how the results of the questionnaire have been used to enhance the original BIOMASS methodology (IAEA Enhanced BIOMASS Methodology Report in press).
Assuntos
Resíduos Radioativos , Radioatividade , Eliminação de Resíduos , Biota , Resíduos Radioativos/análise , Resíduos SólidosRESUMO
This study investigates whether non-human biota are protected against harmful effects of ionizing radiation after a possible future release of radioactive matter from a planned repository for spent nuclear fuel. Radiation dose rates to a broad spectrum of organisms were calculated based on data from sampled organisms and modeled activity concentrations. Calculations were performed with the ERICA Tool, a software program which applies a screening dose-rate value of 10 microgray per hour (µGy h(-1)) for all types of organisms. Dose rates below this value are thought to result in minimal risk to the individual or population. All calculated dose rates were below the screening value and below the lowest relevant band of "derived consideration levels" proposed by the International Commission on Radiological Protection. This provides a sound basis for arguing that no individuals or populations of examined species would be harmfully affected by a possible radioactive release from the repository.
Assuntos
Geologia , Plantas , Poluentes Radioativos , Animais , Exposição AmbientalRESUMO
To assist transport modeling in assessments of the radiological impact of a geological repository for radioactive wastes, the mobility of various elements was studied in arable and wetland soils in the Forsmark region, Sweden. Pore water and total element contents were determined for five types of unconsolidated deposits (regolith), spanning a wide range of soil properties with respect to pH and organic matter content. Two soil depths were sampled to capture element mobility in regolith layers affected and unaffected by soil-forming processes. The solid/liquid partition coefficients (K d values) for most elements varied significantly among regolith types. For most elements, the observed variations in K d values could be explained by variations in soil properties. For many elements, mobility increased with decreasing soil pH. The results provide a significant addition of data on radionuclide retention in soils, taking account of soil properties and processes.
Assuntos
Resíduos Radioativos , Poluentes Radioativos do Solo/química , SoloRESUMO
The radiation doses to humans resulting from a potential release of radionuclides from a geological repository for long-lived waste are assessed over tens or even hundreds of thousands of years. Ingestion is expected to be the major exposure pathway, and the group with the highest exposures will be those that consume the most contaminated food. In this paper, we characterize the group of individuals with the highest exposures by considering the physical and biological characteristics of the contaminated area and human requirements for energy and nutrients. We then calculate intake rates based on land-use scenarios drawn from self-sustained communities spanning prehistoric times to an industrial-age agrarian culture. The approach is illustrated by simulating groundwater release of four radionuclides to an expected discharge area. We argue that the derived intake rates may serve as credible bounding cases when projected doses are evaluated for compliance with regulatory criteria.
Assuntos
Exposição Ambiental , Alimentos , Doses de RadiaçãoRESUMO
Assessments of radiological impacts on humans and other biota from potential releases to the biosphere from a deep geologic repository for spent nuclear fuel are associated with several challenges. Releases, if any, will likely occur in a far future and to an environment that will have experienced substantial transformations. Such releases would occur over very long periods during which environmental conditions will vary continuously due to climate change and ecosystem succession. Assessments of radiological impacts must therefore be based on simulations using models that can describe the transport and accumulation of radionuclides for a large variety of environmental conditions. In this paper we describe such a model and show examples of its application in a safety assessment, taking into account results from sensitivity and uncertainty analyses of the model predictions.
Assuntos
Modelos Teóricos , Poluentes Radioativos/química , Radioisótopos/química , IncertezaRESUMO
BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. In this study, we wanted to elucidate whether SLC6A4 variations is involved in attempted suicide among patients with schizophrenia in a Scandinavian case-control sample. METHODS: Patients diagnosed with schizophrenia from three Scandinavian samples were assessed for presence or absence of suicide attempts, based on record reviews and interview data. Seven SLC6A4 single nucleotide polymorphisms (SNPs) were genotyped in 837 schizophrenia patients and 1,473 control individuals. Association analyses and statistical evaluations were performed with the program UNPHASED (version 3.0.9). RESULTS: We observed an allele association between the SNP rs16965628, located in intron one of SLC6A4, and attempted suicide (adjusted p-value 0.01), among patients with schizophrenia. No association was found to a diagnosis of schizophrenia, when patients were compared to healthy control individuals. CONCLUSION: The gene SLC6A4 appears to be involved in suicidal ideation among patients with schizophrenia. Independent replication is needed before more firm conclusions can be drawn.
Assuntos
Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Psicologia do Esquizofrênico , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Suicídio/psicologia , Adulto , Alelos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Ideação SuicidaRESUMO
BACKGROUND: Patients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine pathway, and its formation indirectly depends on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine. METHODS: We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were selected covering KMO and were analyzed in UNPHASED. RESULTS: We included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA. LIMITATIONS: Given the limited sample size, the results are tentative until replication. CONCLUSION: Our results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA.
Assuntos
Ácido Cinurênico/metabolismo , Quinurenina 3-Mono-Oxigenase/genética , Esquizofrenia/genética , Adulto , Alelos , Encéfalo/metabolismo , Estudos de Associação Genética , Genótipo , Humanos , Quinurenina 3-Mono-Oxigenase/metabolismo , Polimorfismo de Nucleotídeo Único , Esquizofrenia/metabolismoRESUMO
The D-amino acid oxidase activator (DAOA) protein regulates the function of D-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4-dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA, a precursor of dopamine, whereas D-serine participates in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn by lumbar puncture, and the concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms, rs3918342 and rs1421292, were significantly associated with CSF HVA concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA concentrations. None of the polymorphisms were significantly associated with MHPG concentrations. Our results indicate that DAOA gene variation affects dopamine turnover in healthy individuals, suggesting that disturbed dopamine turnover is a possible mechanism behind the observed associations between genetic variation in DAOA and behavioral phenotypes in humans.
Assuntos
D-Aminoácido Oxidase/genética , Ácido Homovanílico/líquido cefalorraquidiano , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , População Branca , Adulto JovemRESUMO
Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in metabolic pathways of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes a common polymorphism (rs1801133 or C677T), which is associated with enzyme activity. The T-allele of the C677T polymorphism has been associated with earlier age at onset of schizophrenia in a Scandinavian population, although no association was found in replication attempts in other populations. Extending the study to five Nordic samples consisting of 2,198 patients with schizophrenia, including the original Scandinavian samples, there was no significant association between MTHFR C677T polymorphism and age at onset in schizophrenia. The present results do not suggest that the investigated MTHFR polymorphism has any significant influence on age at onset of schizophrenia in the Nordic population.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Idade de Início , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Noruega/epidemiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Only a minority of patients treated with antipsychotics in clinical studies continue their treatments throughout a longer study period. Few studies address this issue from a lifetime perspective. In this naturalistic study, we aimed at analysing the prescription pattern of antipsychotic drugs among a sample of Swedish patients with a diagnosis of psychotic illness, from the first contact with psychiatry (typically between 1973 and 1997) until the last written note in the case history documents. A retrospective descriptive analysis was performed of all case history data of 66 patients diagnosed with schizophrenia or related psychotic disorders. Patients with schizophrenia were prescribed antipsychotic medication more than 90% of the time. Each patient generally had been prescribed several (up to 16) different antipsychotic drugs and a quarter of the patients had been prescribed two or more antipsychotics for a third of their prescription time. Patients with psychosis were exposed to a cumulatively growing number of antipsychotics. Various factors, including clinician and patient expectations, and specific strengths and limitations of available antipsychotics may account for frequent medication changes over time.
Assuntos
Antipiréticos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Patients treated with antipsychotic drugs often receive concomitant psychotropic compounds. Few studies address this issue from a lifetime perspective. Here, an analysis is presented of the prescription pattern of such concomitant medication from the first contact with psychiatry until the last written note in the case history documents, in patients with a diagnosis of psychotic illness. METHODS: A retrospective descriptive analysis of all case history data of 66 patients diagnosed with schizophrenia or schizophrenia-like psychotic disorders. RESULTS: Benzodiazepines and benzodiazepine-related anxiolytic drugs had been prescribed to 95% of the patients, other anxiolytics, sedatives or hypnotic drugs to 61%, anti-parkinsonism drugs to 86%, and antidepressants to 56% of the patients. However, lifetime doses were small and most of the time patients had no concomitant medication. The prescribed lifetime dose of anti-parkinsonism drugs was associated with that of prescribed first-generation but not second-generation antipsychotics. CONCLUSIONS: Most psychosis patients are sometimes treated with concomitant drugs but mainly over short periods. Lifetime concomitant add-on medication at the individual patient level is variable and complex but not extensive.
Assuntos
Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Psicotrópicos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Antiparkinsonianos/uso terapêutico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Quimioterapia Combinada , Feminino , Hospitais Urbanos , Humanos , Hipnóticos e Sedativos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Estudos Retrospectivos , Suécia , Adulto JovemRESUMO
The question of a potential biological sexual signature in the human brain is a heavily disputed subject. In order to provide further insight into this issue, we used an evolutionary approach to identify genes with sex differences in brain expression level among primates. We reasoned that expression patterns important to uphold key male and female characteristics may be conserved during evolution. We selected cortex for our studies because this specific brain region is responsible for many higher behavioral functions. We compared gene expression profiles in the occipital cortex of male and female humans (Homo sapiens, a great ape) and cynomolgus macaques (Macaca fascicularis, an old world monkey), two catarrhine species that show abundant morphological sexual dimorphism, as well as in common marmosets (Callithrix Jacchus, a new world monkey) which are relatively sexually monomorphic. We identified hundreds of genes with sex-biased expression patterns in humans and macaques, while fewer than ten were differentially expressed between the sexes in marmosets. In primates, a general rule is that many of the morphological and behavioral sexual dimorphisms seen in polygamous species, such as macaques, are typically less pronounced in monogamous species such as the marmosets. Our observations suggest that this correlation may also be reflected in the extent of sex-biased gene expression in the brain. We identified 85 genes with common sex-biased expression, in both human and macaque and 2 genes, X inactivation-specific transcript (XIST) and Heat shock factor binding protein 1 (HSBP1), that were consistently sex-biased in the female direction in human, macaque, and marmoset. These observations imply a conserved signature of sexual gene expression dimorphism in cortex of primates. Further, we found that the coding region of female-biased genes is more evolutionarily constrained compared to the coding region of both male-biased and non sex-biased brain expressed genes. We found genes with conserved sexual gene expression dimorphism in the occipital cortex of humans, cynomolgus macaques, and common marmosets. Genes within sexual expression profiles may underlie important functional differences between the sexes, with possible importance during primate evolution.
Assuntos
Callithrix/genética , Córtex Cerebral/metabolismo , Sequência Conservada , Evolução Molecular , Macaca fascicularis/genética , Lobo Occipital/metabolismo , Caracteres Sexuais , Motivos de Aminoácidos/genética , Animais , Córtex Cerebral/química , Sequência Conservada/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Lobo Occipital/química , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Methylenetetrahydrofolate reductase (MTHFR) is involved in the one-carbon cycle, which is of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes two common polymorphisms (rs1801133 or C677T; rs1801131 or A1298C) which both alter enzyme activity. The T-allele of the C677T polymorphism has recently been associated with earlier age at onset of schizophrenia. In the present study we examined the association between the MTHFR C677T and A1298C polymorphisms and age at onset of schizophrenia in twelve samples consisting of 3,213 unrelated schizophrenia patients, including the original Scandinavian sample. There was no consistent relationship between MTHFR C677T, A1298C or combined 677T/1298C carriers and age of onset in schizophrenia when the results of each study were combined using meta-analysis. The present results suggest that the investigated MTHFR polymorphisms do not influence age of onset in schizophrenia.
Assuntos
Idade de Início , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Esquizofrenia/genética , Alelos , Ciclo do Carbono , Feminino , Humanos , Masculino , Metanálise como Assunto , População Branca/genética , Adulto JovemRESUMO
BACKGROUND: Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder. METHODS: We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography. RESULTS: Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers. LIMITATIONS: The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease. CONCLUSION: Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder.
Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Bipolar/psicologia , Ácido Cinurênico/líquido cefalorraquidiano , Adulto , Fatores Etários , Transtorno Bipolar/diagnóstico , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n=132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIAA and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five-allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects.
Assuntos
Ácido Homovanílico/líquido cefalorraquidiano , Indóis/líquido cefalorraquidiano , Polimorfismo Genético/genética , Triptofano Hidroxilase/genética , Adolescente , Adulto , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Adulto JovemRESUMO
Relationships between prefrontal and temporal lobe grey matter volumes as assessed by magnetic resonance imaging and neurocognitive test results have been reported in schizophrenia. This investigation aimed to localize brain regions where cortical thickness and neurocognitive performance were related, and investigate if such relationships might differ in schizophrenia patients and healthy controls. Sixty-seven patients with schizophrenia and 69 healthy controls were characterized by neurocognitive testing and by brain cortical thickness maps. Putative cortical thickness/cognitive score relationships were investigated with contrast analyses of general linear models for the combined sample. Regions in which relationships were present were further investigated for diagnostic interaction. In the combined sample, significant positive relationships were found between frontal, temporal and occipital regions and tests for verbal IQ, verbal learning and executive functions. Diagnostic interaction was found for the relationships between verbal IQ and the right temporo-occipital junction and the left middle occipital gyrus. In conclusion, the significant relationships between cortical thickness and neurocognitive performances were localized in brain areas known to be involved in cognition. The relationships were similar in patients and controls, except for the right temporo-occipital and left occipital cortical areas, indicating a disrupted structure-function relationship in patients with schizophrenia compared to healthy control subjects.
Assuntos
Córtex Cerebral/patologia , Transtornos Cognitivos/etiologia , Esquizofrenia/complicações , Esquizofrenia/patologia , Adulto , Mapeamento Encefálico , Função Executiva/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética/métodos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Aprendizagem Verbal/fisiologiaRESUMO
Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Adolescente , Adulto , Idade de Início , Alelos , Estudos de Casos e Controles , China , Saúde da Família , Feminino , Humanos , Masculino , Fatores de Risco , Países Escandinavos e Nórdicos , Esquizofrenia/epidemiologiaRESUMO
Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P = 0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218/A779 locus increases the susceptibility of schizophrenia in Caucasian and Asian populations. In addition, the data at hand suggest that the locus contributes to the liability of psychiatric disorders characterized by elevated suicidal rates, rather than affecting suicidal behavior of individuals suffering from a psychiatric disorder.
Assuntos
Predisposição Genética para Doença , Esquizofrenia/genética , Suicídio , Triptofano Hidroxilase/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Serotonina/farmacologia , Tentativa de SuicídioRESUMO
Climate change is predicted to have far reaching consequences for the mobility of carbon in arctic landscapes. On a regional scale, carbon cycling is highly dependent on interactions between terrestrial and aquatic parts of a catchment. Despite this, studies that integrate the terrestrial and aquatic systems and study entire catchments using site-specific data are rare. In this work, we use data partly published by Lindborg et al. (2016a) to calculate a whole-catchment carbon mass-balance budget for a periglacial catchment in West Greenland. Our budget shows that terrestrial net primary production is the main input of carbon (99% of input), and that most carbon leaves the system through soil respiration (90% of total export/storage). The largest carbon pools are active layer soils (53% of total carbon stock or 13 kg C m-2), permafrost soils (30% of total carbon stock or 7.6 kg C m-2) and lake sediments (13% of total carbon stock or 10 kg C m-2). Hydrological transport of carbon from the terrestrial to aquatic system is lower than in wetter climates, but the annual input of 4100 kg C yr-1 (or 3.5 g C m-2 yr-1) that enters the lake via runoff is still three times larger than the eolian input of terrestrial carbon. Due to the dry conditions, the hydrological export of carbon from the catchment is limited (5% of aquatic export/storage or 0.1% of total export/storage). Instead, CO2 evasion from the lake surface and sediment burial accounts for 57% and 38% of aquatic export/storage, respectively (or 0.8% and 0.5% of total export/storage), and Two-Boat Lake acts as a net source of carbon to the atmosphere. The limited export of carbon to downstream water bodies make our study system different from wetter arctic environments, where hydrological transport is an important export pathway for carbon.