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W Maier

Publications and source records attributed to W Maier.

At least 163 records · Page 9Linked to original sources
PubMed2000

Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls.

The tryptophan hydroxylase (TPH) gene encodes for the rate-limiting enzyme of the serotonin metabolism and, therefore, has to be considered a major candidate for association studies in affective disorders. Recently, an association between this gene and bipolar affective disorder has been reported in a French population. We sought to replicate this finding in a German sample. Allele frequencies of a biallelic polymorphism (A218C) of the TPH gene were determined in 95 bipolar I patients and their parents. Preferential transmission of alleles from heterozygous parents to bipolar offspring was tested with the "transmission disequilibrium test" (TDT), which eliminates the contribution of population stratification to an association finding. Our sample yielded a power >90% to detect the originally reported effect. Neither allele 218A nor allele 218C were preferentially transmitted from heterozygous parents to bipolar offspring. Our results, therefore, do not support the hypothesis that the TPH gene is involved in the etiology of bipolar disorder.

Adult↗
PubMed2000

Association between an interleukin-6 promoter and 3' flanking region haplotype and reduced Alzheimer's disease risk in a German population.

Several studies have demonstrated that interleukin-6 (IL-6) is involved in the pathogenesis of Alzheimer's disease (AD). We previously reported on an association between the C allele of a variable number of tandem repeat polymorphism in the 3' flanking region of IL-6 gene (IL-6vntr) and delayed initial onset and reduced AD risk. A novel G/C polymorphism at position -174 in the IL-6 gene promoter (IL-6prom) has recently been identified and appears to influence the regulation of IL-6 expression. We examined this functional polymorphism in 102 AD patients and two control groups of 191 healthy subjects and 160 depressed patients. There was no evidence for an allelic association between IL-6prom polymorphism and earlier age of onset or risk of AD. However, haplotype analysis showed a strong linkage disequilibrium between IL-6vntr and IL-6prom and demonstrated an interaction between IL-6vntr and IL-6prom which modifies AD risk.

Alleles↗
PubMed2000

Investigation of the human serotonin 6 [5-HT6] receptor gene in bipolar affective disorder and schizophrenia.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of central nervous functions by activating multiple 5-HT receptor subtypes. A possible irregularity of serotonergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study, we performed a systematic mutation scan of the complete coding region and splice junctions of the 5-HT(6) receptor gene to explore the contribution of this gene to the development of bipolar affective disorder and schizophrenia. Investigating 137 unrelated individuals (including 45 bipolar affective patients, 46 schizophrenic patients, and 46 unrelated controls), we identified six single base substitutions (126G/T, 267C/T, 873+30C/T, 873+128A/C, 1128G/C, 1376T/G). Comparing frequencies between patients and controls, we observed a significant overrepresentation of the 267C allele among bipolar patients (P=0. 023 not corrected for multiple testing). This finding was followed up in an independent sample of 105 bipolar family trios using a family-based association design. Fifty-one transmissions could be examined. In 30 cases allele 267C and in 21 cases allele 267T were transmitted to the affected offspring. Although this result was far from statistical significance (transmission disequilibrium test=1.59, P=0.208), the limited number of possible transmissions may have prevented detection of smaller effects. Our preliminary data suggest that bipolar affective disorder may be associated with variation in the 5-HT(6) gene. It will be important to extend the present analysis to larger samples. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:217-221, 2000.

Bipolar Disorder↗
PubMed2000

Mechanical compression of coronary artery stents: potential hazard for patients undergoing cardiopulmonary resuscitation.

Mechanical compression of coronary artery stents may be associated with a fatal outcome as the result of refractory myocardial ischemia. We present the history of an 83-yr-old patient, who died owing to hemorrhagic shock 3 days after stent implantation, despite immediate cardiopulmonary resuscitation (CPR). Postmortem examination showed stent compression, probably due to mechanical deformation during CPR. This complication has been reported in two other cases in the literature, suggesting that CPR may be hazardous to patients with coronary artery stents.

Aged↗
PubMed2000

Dopamine D3 receptor variant and tardive dyskinesia.

In the search for genetic factors contributing to tardive dyskinesia, dopamine receptor genes are considered major candidates. The dopamine D3 receptor is of primary interest as dopamine D3 receptor knock-out mice show locomotor hyperactivation resembling extrapyramidal side-effects of neuroleptic treatment. Furthermore, Steen and colleagues (1997) recently reported an association between tardive dyskinesia and a dopamine D3 receptor gene variant. In the present study we tried to replicate this finding. We investigated 157 patients with schizophrenia or schizoaffective disorder receiving long-term neuroleptic medication who never or persistently displayed tardive dyskinesia. As advanced age is a main risk factor for tardive dyskinesia, we also compared older patients with a long duration of schizophrenia not displaying tardive dyskinesia to younger patients with a shorter duration of the illness displaying tardive dyskinesia. However, we found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia.

Adult↗
PubMed2000

[Reliability and validity of the German version of the Premorbid Adjustment Scale (PAS)].

The Premorbid Adjustment Scale (PAS) was developed by Cannon-Spoor et al. 1982 for research use and has gained importance internationally. This scale is designed to measure the extent of attaining developmental goals premorbidly. The German version is presented here, with first data on the reliability and validity of the scale. In a sample of schizophrenic and schizoaffective patients (n = 86) and healthy parents of the patients (n = 38), DSM-IV diagnosis was made and PAS and Positive and Negative Syndrome Scale (PANSS) data were taken along with information on the course of the disorder. Using Cronbachs alpha, the estimated reliability for the scale and subscales lay between 0.809 and 0.931. High PAS scores, representing poor premorbid adjustment, correlated significantly with low age of onset, high PANSS scores, insidious onset, long hospitalisation, and serious course of the disorder. The threshold of PAS scores between healthy and sick probands was at 0.23. Patients with scores > 0.53 appeared to have an unfavourable course. With test results > 0.23, an odds ratio of 27.9 was ascertained (95% CI 9.39-82.89). The findings presented correspond with those from previous reports in literature.

Adolescent↗
PubMed2000

The genetic epidemiology of schizophrenia and of schizophrenia spectrum disorders.

It has been known for a long time that schizophrenia and several related psychopathological traits aggregate in families on a common genetic basis. Improved methodology of recent family, twin and adoption studies has led to a better unterstanding of which psychopathologically defined syndromes and personality traits are part of a schizophrenia spectrum, and to which degree individual spectrum conditions share the same genetic background with schizophrenia. The spectrum concept has been extended to include neuropsychologically, neurophysiologically and neuroradiologically measurable familial traits as subclinical endophenotypes of schizophrenia that may be more fundamental to the development of the disease than overt psychopathology. This knowledge has been useful in designing molecular genetic linkage and association studies that aim at directly identifying individual risk genes. Replicable linkage findings have emerged from genome scans that imply at least seven chromosomal regions to harbour schizophrenia susceptibility genes. They strengthen the conviction that schizophrenia is indeed a genetically complex disorder, based on a larger number of susceptibility genes with risk-increasing alleles that are common in the population and exert a limited effect on the individual level. Although demanding increased investments into sample collection, genotyping and computational technology, identification of these genetic variants will be possible and worthwhile since they may have a large effect in terms of population attributable risk.

Alleles↗
PubMed2000

Secondary products in mycorrhizal roots of tobacco and tomato.

Colonization of the roots of various tobacco species and cultivars (Nicotiana glauca Grah., N. longiflora Cav., N. rustica L., N. tabacum L., N. tabacum L. cv. Samsun NN, N. sanderae hort. Sander ex Wats.) as well as tomato plants (Lycopersicon esculentum L. cv. Moneymaker) by the arbuscular mycorrhizal fungus Glomus intraradices Schenck and Smith resulted in the accumulation of several glycosylated C13 cyclohexenone derivatives. Eight derivatives were isolated from the mycorrhizal roots by preparative high performance liquid chromatography (HPLC) and spectroscopically identified (MS and NMR) as mono-, di- and triglucosides of 6-(9-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one and monoglucosides of 6-(9-hydroxybutyl)-1,5-dimethyl-4-cyclohexen-3-one-1-carboxylic acid and 6-(9-hydroxybutyl)-1,1-dimethyl-4-cyclohexen-3-one-5-carboxylic acid. In contrast to the induced cyclohexenone derivatives, accumulation of the coumarins scopoletin and its glucoside (scopolin) in roots of N. glauca Grah. and N. tabacum L. cv. Samsun NN, was markedly suppressed.

Chromatography, High Pressure Liquid↗
PubMed2000

Asthma inhaler use and barriers in a population-based sample of African-American and white adolescents.

BACKGROUND: There is little information on inhaler medication and barriers to use among a population-based sample of adolescents and whether possible variations in asthma treatment by ethnic group exist. OBJECTIVE: We describe the prevalence of inhaler use and identify barriers for proper use of asthma medication in a population-based sample of adolescents of which 34% are African-American. METHODS: A cross-sectional survey using the ISAAC (International Survey of Asthma and Allergies in Children) questionnaire was conducted in a school population-based sample (n = 2056) of 13 to 14-year-old eight grade students in the Charlotte-Mecklenburg, North Carolina public school system. Questions were asked about symptom prevalence, asthma diagnosis, inhaler use, and barriers to care. RESULTS: Fourteen percent of the children (296/2056) reported using an inhaler in the last 12 months with no differences among African-American children and white children. Twenty-six percent of inhaler users were not allowed to carry their medication on their person while at school. Girls were more likely to be allowed to carry their inhalers at school and diagnosed asthmatic girls had a higher prevalence of wheezing in the last year (47%) compared with diagnosed asthmatic boys (35%). Smoking prevalence was higher in inhaler users (26%) compared to the study population (19%). CONCLUSIONS: Inhaler use is high in this population. Adolescents using inhalers need to reduce their smoking levels. Schools need to reevaluate their policies on the use of inhalers at school.

Adolescent↗
PubMed2000

Advanced parental age: a risk factor for Alzheimer's disease or depression in the elderly?

BACKGROUND: Advanced parental age has been suggested as a risk factor for Alzheimer's disease (AD) as well as for other psychiatric disorders. In the present investigation, a sample of gerontopsychiatric patients was examined for a possible parental age effect. STUDY POPULATION AND METHODS: Eighty-three patients with AD, 154 elderly patients with depressive episodes, and 48 comorbid patients (AD and depressive episode) as well as 107 age-matched healthy control subjects from the general population were included in the investigation. Information on the years of birth of the parents was derived from personal or family history information. RESULTS: The mean maternal and paternal ages at the time of birth of the index subject were not significantly different for the different diagnostic subgroups or for the control sample. CONCLUSION: There was no evidence in our sample that advanced parental age increases the risk of AD or depression in the elderly.

Aged↗
PubMed2000

Generalized anxiety disorder (ICD-10) in primary care from a cross-cultural perspective: a valid diagnostic entity?

OBJECTIVE: Generalized anxiety disorder (GAD) is a common psychiatric disorder. The nosological status of this diagnostic entity was critically discussed because of the very high rate of comorbidity with other psychiatric disorders, the assumed low degree of social disability associated with GAD in the absence of other disorders, and an ambigious definition. METHOD: We explored the frequency and associated social disability of GAD, and examined whether the ICD-10 definition of GAD is appropriate. The analysis was based on the WHO study on 'Psychological Problems in Primary Care' conducted in a standardized manner in 14 countries. RESULTS: We found GAD (total and without another psychiatric disorder) to be common in primary care in nearly all countries (mean 1-month prevalence rate, 7.9%), with about 25% of these cases presenting with GAD in the absence of any comorbid psychiatric disorder. GAD in general, as well as non-comorbid GAD, are associated with social disability which is as severe as that in chronic somatic diseases. CONCLUSION: It remains questionable whether the current ICD-10 diagnosis of GAD defining 6 months as a minimum duration and requiring at least four associated symptoms for diagnosis is the most appropriate option. Using this definition, a substantial proportion of psychosocially disabled subjects characterized by anxiety, tension and worrying remain undetected, and are possibly therefore not adequately treated.

Anxiety Disorders↗
PubMed2000

DRD4 exon III VNTR polymorphism-susceptibility factor for heroin dependence? Results of a case-control and a family-based association approach.

Dopaminergic abnormalities are implicated in the pathogenesis of substance abuse.1 Recently, two reports have been published suggesting an association between opioid dependence and presence of long alleles of the dopamine D4 receptor (DRD4) gene exon III VNTR.2, 3 We have attempted to replicate this finding using a two-tiered strategy employing independent case-control and family-based association samples. Our study was possibly the largest candidate gene association study to date on opioid dependence in a sample of 815 subjects, 396 of whom were patients. We found long alleles of the DRD4 exon III VNTR in similar frequency among 285 heroin addicts and 197 controls. Furthermore, no preferential transmission of long alleles to affected offspring was observed in a sample of 111 patients and their parents. Our results, therefore, do not support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for opioid dependence in man. Molecular Psychiatry(2000) 5, 101-104.

Adult↗
PubMed2000

Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings.

The serotonergic (5-HT) system has been implicated in the etiopathogenesis of psychoses. Since the 5-HT transporter plays an important role in regulation of 5-HT transmission, its gene can be considered as a candidate for vulnerability to psychiatric disorders. Two polymorphic sites of the 5-HT transporter gene-5-HTTLPR, a VNTR in the 5' regulatory region, and a VNTR in the second intron-were studied in a sample of 61 families with schizophrenia for transmission disequilibrium. Each family contained at least two siblings affected with schizophrenia or schizoaffective disorder (mainly schizophrenic). One hundred and thirty-nine affected offspring with parental information for genotyping, were available for analysis. No preferential transmission of either short or long alleles of the promoter polymorphism was observed. However, a transmission distortion was detected for alleles of the intronic VNTR polymorphism (chi2TDT max =14.33; P = 0.0002; corrected P value = 0.0003) resulting in more frequent than expected transmission of the 12 repeat allele. This finding adds additional evidence to the idea that the serotonergic system may be involved in development of psychoses. Molecular Psychiatry (2000) 5, 91-95.

Brain Chemistry↗
PubMed2000

Confirmation of the association between bleomycin hydrolase genotype and Alzheimer's disease.

Bleomycin hydrolase (BH), a cysteine protease from the papain superfamily, is considered to be a candidate for the beta-secretase, which is presumably involved in the production of beta-amyloid peptide. The G/G genotype of BH was identified as a significant risk factor for the development of Alzheimer's disease (AD) in subjects not carrying the apolipoprotein E epsilon4 allele (apoE-epsilon4). However, this finding was recently challenged. We studied this polymorphism in a homogenous sample of German AD patients and controls. The over-representation of the G/G genotype in AD patients could be confirmed, however it was more pronounced in apoE-epsilon4 carriers. Additional studies should be undertaken to increase the confidence that the BH polymorphism is associated with AD and to explore the relationship between BH and apoE.

Aged↗
PubMed2000

Systematic screening for DNA sequence variation in the coding region of the human dopamine transporter gene (DAT1).

The dopamine transporter (DAT) plays a central role in dopaminergic neurotransmission in the human brain. Genetic association studies have used a variable number of tandem repeat (VNTR) polymorphism in the 3'-flanking region of the dopamine transporter gene (DAT1) to implicate the DAT in the development of various neuropsychiatric disorders. In this study, we have examined the possibility that a mutation exists in the coding region of the DAT1 gene which through linkage disequilibrium accounts for the observed associations. The complete coding region, as well as exon-intron boundaries, was screened in 91 unrelated individuals including 45 patients with bipolar affective disorder and 46 healthy control individuals by the means of single strand conformation analysis. Our findings suggest that the DAT1 gene is highly conserved since we detected only two rare missense substitutions (Ala559Val, Glu602Gly) and three silent mutations (242C/T, 1342A/G, and 1859C/T) in the whole coding region. Five sequence variants were observed in intronic sequences but none affects known splice sites. The lack of frequent variants of possible functional relevance indicates that genetic variation in the coding region of the DAT1 gene is not responsible for the previously observed associations with neuropsychiatric disorders. The two rare missense substitutions were found in single bipolar patients but not in controls. Investigation of the patients' families revealed independent segregation between the Ala559Val variant and affective disorder. The Glu602Gly variant was inherited by the proband from an affected father. It therefore remains possible that Glu602Gly may be a rare cause of bipolar affective disorder.

Amino Acid Substitution↗
PubMed2000

A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6.

Evidence from epidemiological studies and segregation analysis suggests oligo- or polygenic inheritance in schizophrenia. Since model independent methods are thought to be most appropriate for linkage analysis in complex disorders, we performed a genome-wide autosomal screen in 71 families from Germany and Israel containing 86 independent affected sib-pairs with parental genotype information for statistical analysis strictly identity by descent. We genotyped 305 individuals with 463 markers at an average distance of approximately 10 cM genome-wide, and 1-2 cM in candidate regions (5q, 6p, q, 8p, 10p, 18p, 22q). The highest multipoint LOD scores (ASPEX) were obtained on 6p (D6S260, LOD = 2.0; D6S274, LOD = 2.2, MHC region, LOD = 2.15) and on 10p (D10S1714, LOD = 2.1), followed by 5q (D5S2066, LOD = 1.36), 6q (D6S271, LOD = 1.12; D6S1613, LOD = 1.11), 1q (D1S2675, LOD = 1.04), and 18p (broad disease model: D18S1116, LOD = 1.0). One hundred and thirty-three additional family members were available for some of the families (extended families) and were genotyped for these regions. GENEHUNTER produced a maximum NPL of 3.3 (P = 0.001) for the MHC region and NPL of 3.13 (P = 0.0015) for the region on 10p. There is support for these regions by independent groups. In genome-wide TDT analysis (sTDT, implemented in ASPEX), no marker passed the significance level of 0.0001 given by multiple testing, but nominal significance values for D10S211 (P = 0.03) and for GOLF (P = 0.0032) support further the linkage results on 10p and 18p. Our survey of 22 chromosomes identified candidate regions which should be useful to screen for schizophrenia susceptibility genes.

Chromosome Mapping↗