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Biomedical subjects

W Maier

Publications and source records attributed to W Maier.

At least 217 records · Page 12Linked to original sources
PubMed1999

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder.

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.

Alleles↗
PubMed1999

Internal and external validity of the WHO Well-Being Scale in the elderly general population.

The objectives of this study were (i) to evaluate the validity of the WHO Well-Being Scale in elderly subjects and (ii) to assess the influence of demographic variables on subjective quality of life. A sample of 254 elderly subjects completed the 22-item WHO Well-Being Scale. The scale had an adequate internal and external validity. However, the short 10-item and 5-item versions were equally valid. Low scores indicating decreased well-being were related to the presence of a psychiatric disorder or, independently, to poor living conditions. The Well-Being Scale and their short versions would appear to be useful instruments for identifying subjects with reduced subjective quality of life.

Adult↗
PubMed1999

Diagnostic and therapeutic management of bilateral carotid artery occlusion caused by near-suicidal hanging.

In cases of attempted suicide by hanging, a combination of mechanisms causing local destruction of the pharynx, larynx, vessels, and spine, as well as neurologic complications, has to be considered. We present a case of hanging in which a deeply unconscious patient without any palpaple pulsation of the carotid arteries was referred to our otolaryngology department. Computed tomography and angiography showed parapharyngeal air, complete obstruction of both common carotid arteries, and a compensatory circulation through the vertebral arteries. Three hours after the trauma, surgical exploration with resection of the enrolled intima of both carotid arteries and repair of the pharynx was performed. The patient awoke with an infarct of the right hemisphere with incomplete left hemiparesis the next day, but symptoms slowly declined during the following months, and the patient learned swallowing again perfectly. We conclude from our experience that in near-hanged patients a prompt onset of adequate diagnostic and therapeutic measures is mandatory, as good neurologic and functional results may occur even in cases with coma and severe destruction of the carotid arteries and pharyngeal and laryngeal structures. Surgical repair of blunt carotid lesions is recommended and may be crucial for a good outcome.

Carotid Artery Injuries↗
PubMed1999

The epidemiology of comorbidity between depression, anxiety disorders and somatic diseases.

Depression, generalized anxiety disorder and somatoform disorder are the most common psychiatric disorders in primary care and in the general population. These disorders also show an excess comorbidity which is substantially more common than expected on the basis of their prevalence rates both in primary care as well as in general population. There is no unique mechanism accounting for each of these excess comorbidity constellations. Multiple consequences underline the clinical relevance of comorbidity between these disorders: more psychosocial disability, substantially elevated risk for completed suicides and suicide attempts, worse clinical outcome and treatment response. Recognition of comorbidity is essential for improvement of treatment.

Anxiety Disorders↗
PubMed1999

hSKCa3: no association of the polymorphic CAG repeat with bipolar affective disorder and schizophrenia.

hSKCa3 is a neuronal small conductance calcium-activated potassium channel, which contains a polyglutamine tract, encoded by a polymorphic CAG repeat in the gene. Since an association between longer alleles of this CAG repeat and bipolar disorder or schizophrenia has been reported, we genotyped the polymorphic CAG repeat in 91 German family trios of patients with bipolar disorder I and used the transmission disequilibrium test (TDT) to test for association. Applying a dichotomized model (< or = 19 or > 19 CAG triplets), we found no evidence for an association of longer alleles with bipolar disorder (TDT = 0.75, P = 0.386). Regarding the whole range of alleles, there was no preference in transmitting the larger of the two observed alleles from parents to the affected offspring. In parallel we performed an independent case-control study on German patients with bipolar disorder and schizophrenia. Again we did not detect an overrepresentation of longer CAG repeats in patients. Thus, our data do not support the hypothesis that longer CAG repeats in the hSkCa3 gene contribute to the susceptibility for bipolar disorder and schizophrenia.

Adult↗
PubMed1998

Age at onset and gender resemblance in bipolar siblings.

In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific.

Adolescent↗
PubMed1998

Genotype-phenotype relationship in female carriers of the premutation and full mutation of FMR-1.

The present French-German cooperative study focuses on the genotype-phenotype relationship of mutations of the FMR-1 gene and psychiatric conditions in mothers with a full mutation in the FMR-1 gene of fra-X children (n=13), mothers with a premutation in the FMR-1 gene of fra-X children (n=61), as well as premutated siblings of these mothers without affected children (n=17) and two non-mutated control groups: (1) siblings of these mothers with normal CGG repeat (n=18); and (2) mothers of non-fra-X autistic children (n=42). Mothers with a full mutation in the FMR-1 gene and mothers with a premutation in the FMR-1 gene did not differ in the frequency of any axis I disorder; however, both groups were diagnosed with social phobia more often than the control group of mothers of autistic children. Moreover, mothers with a premutation in the FMR-1 gene of fra-X children and their siblings with the premutation (without affected offspring) revealed a similar frequency of social phobia. Furthermore avoidant personality disorder was more common in groups of carriers of the full premutation than in siblings without mutation or than the control group of mothers with autistic children. On the basis of our data, we therefore suggest that social avoidance (expressed as social phobia or avoidant personality disorder) has been underestimated in previous studies of carriers with the FMR-1 full mutation or premutation. Comorbidity of axis I and axis II psychiatric diagnoses was mainly restricted to the group of carriers of the full mutation and carriers of the premutation of FMR-1. Correlations between size of CGG repeat and IQ as well as CGG and age of onset of axis I diagnosis were non-significant. IQ of subjects had no impact on presence or absence of axis I and/or axis II diagnoses.

Adult↗
PubMed1998

Further evidence for a susceptibility locus on chromosome 10p14-p11 in 72 families with schizophrenia by nonparametric linkage analysis.

Recent reports on potential linkage by Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557], and by Straub et al. [1997: Am J Med Genet 74:558], prompted us to study chromosome 10 in a sample of 72 families containing 2 or more affected sibs with schizophrenia for additional evidence of linkage. We obtained highest allele sharing for the two markers D10S582 (61.5% allele sharing, chi2 = 7.6, P = 0.0058) and D10S1423 (59% allele sharing, chi2 = 4.76, P = 0.029). D10S1423 is one of the markers with the highest lod scores in the study of Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557]. GENEHUNTER analysis revealed a nonparametric lod score (NPL) of 3.2 (P = 0.0007) for the marker D10S1714, which lies in the same region. Multipoint affected sib-pair lod score analysis (identity by descent) calculated by ASPEX revealed a lod score of 1.72 for all possible sib-pair combinations (107) and of 2.13, when only independent sib-pairs (87) were counted. Our study provides further evidence for a potential susceptibility locus for schizophrenia on chromosome 10p.

Alleles↗
PubMed1998

Results of a genome-wide genetic screen for panic disorder.

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q).

Adolescent↗
PubMed1998

Adenosine A1 receptor and bipolar affective disorder: systematic screening of the gene and association studies.

In the present study we sought to identify genetic variation in the adenosine A1 receptor (A1AR) gene on chromosome 1q31-32.1, which through alteration of protein function or level of expression might contribute to the genetic predisposition to bipolar affective disorder. We performed a systematic mutation scan of the whole coding sequence as well as 5' and 3' untranslated regions by means of single-strand conformation analysis. The region upstream to the coding sequence we investigated contains two functional promoters. Screening 42 patients with bipolar affective disorder, we detected 11 DNA sequence variants (48T/A, 267 + 275C/T, 805T/G, 1777C/A, 1827C/T, 1904C/T, 2126G/T, 2294insT, 2776C/T, 2777del36, 2819T/G). Determining the frequency of these variants in 42 anonymous blood donors, we observed a non-significant (P < 0.06) trend towards an underrepresentation of the 2126T variant in patients when compared to controls. On the other hand, the 2777del36 and the 2819G variant were not found among the controls. These findings were followed up in a large independent replication sample. However, we were not able to confirm the initial findings in the second sample. Our data suggest that genetically determined variation of the A1AR and its two promoters do not play a major role in the development of bipolar affective disorder.

Base Sequence↗
PubMed1998

[Dementia screening in routine clinical practice. A comparative analysis of MMSE, SIDAM and ADAS].

Dementia-screening in clinical routine requires short, sensitive and specific tools. A number of standardized instruments are available for this purpose. The present study analysed the relationship between size of three exemplary dementia-screening tests and their diagnostic accuracy. The Mini-Mental-State-Examination (MMSE), the Structured Interview for the Diagnosis of Dementia of the Alzheimer-type, Multiinfarct Dementia and Dementias of other Aetiologies according to ICD-10 and DSM-III-R (SIDAM) and the Alzheimer's Disease Assessment Scale (ADAS) were applied to 71 patients with dementia of the Alzheimer-type and 73 non-demented controls. A ROC-analysis revealed that neither SIDAM nor ADAS differentiated better between demented and non-demented probands than the MMSE. This was also true for patients with mild dementia. In dementia staging the more comprehensive instruments did not surpass the MMSE, too. Due to it's brevity, the MMSE is the preferential screening-instrument for clinical routine.

Aged↗
PubMed1998

Reliability of interview information in a family study in the elderly.

The aim of the present study was to evaluate the combined test-retest and interrater reliability of different psychiatric lifetime diagnoses yielded in the course of a family study in elderly patients and controls. The following interviews and questionnaires were used in combination: the Composite International Diagnostic Interview (CIDI), the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias of Other Aetiology (SI-DAM), the General Health Questionnaire (GHQ-12) and questionnaires for neurasthenia and recurrent brief depression (RBD). Depressive and dementia disorders can be diagnosed with good reliability in a family study setting with the use of these instruments. The diagnoses of phobic disorders, neurasthenia, RBD, subthreshold RBD and psychiatric caseness as indicated by GHQ-12 scores were less reliable in this setting and are therefore less suitable for use in family studies.

Adult↗
PubMed1998

Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not predispose to schizophrenia.

The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of malformations in various organs including the brain. A polymorphism in the TSC2 gene has been found to be increased in gangliogliomas, a lesion which is associated with disturbed neuro-glial cell migration pattern. Since these pathomorphological changes are compatible with disturbed neuronal migration in schizophrenic brains, we investigated this polymorphism in 130 families with a schizophrenic index patient. A 222-bp fragment of genomic DNA containing the TSC2 variant was analyzed by SSCP. The analysis revealed that there is no association with schizophrenia.

Adult↗
PubMed1998

Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease.

Several lines of evidence suggest a contribution of adenosinergic neurotransmission to the development of panic disorder. We therefore hypothesized that variation in the A1 and A2a adenosine receptor (AR) genes modifies genetic susceptibility to panic disorder. To test this hypothesis, we screened 38 patients with panic disorder for mutations in the coding sequence of the A1AR and A2aAR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched controls. One silent mutation (716T/G) in the A1AR gene and two silent mutations (432C/T and 1083C/T) in the A2aAR gene were detected. The association sample shows a significant association between the 1083T allele (P=0.01) and 1083T/T genotype (P=0.024) of the A2AR gene and panic disorder. Our findings thus lend further support to the hypothesis that the A2aAR gene, or a locus in linkage disequilibrium with it, confers susceptibility to panic disorder. Replication studies in independent samples with nuclear families applying the transmission disequilibrium test (TDT) are warranted.

DNA Primers↗