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Biomedical subjects

R Heun

Publications and source records attributed to R Heun.

At least 55 records · Page 3Linked to original sources
PubMed2000

Identical distribution of the alpha 2-macroglobulin pentanucleotide deletion in subjects with Alzheimer disease and controls in a German population.

Recently, an association between a deletion polymorphism in the alpha 2-macroglobulin gene (A2M) and Alzheimer disease (AD) has been reported. The aim of the present study was to corroborate this association in a German population of 102 AD patients and two control samples of 191 healthy subject and 160 depressed patients. The frequency of the A2M genotype in AD patients was almost identical to that in both control samples. Logistic regression analysis revealed an effect of age and the APOE genotype on AD risk, but no effect of the A2M genotype. Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:775-777, 2000.

Aged↗
PubMed2000

Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder.

Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.

Adult↗
PubMed2000

No association of serum levels of interleukin-6 and its soluble receptor components with a genetic variation in the 3'flanking region of the interleukin-6 gene in patients with multiple sclerosis.

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that a variable number tandem repeat (vntr) polymorphism in the 3'flanking region of the IL-6 gene (C allele) is associated with altered activity of IL-6 in vivo. Therefore, we analyzed the frequency distribution of IL-6 gene C allele vntr poymorphism in 96 MS patients and 106 ethnically matched healthy controls. Moreover, possible correlations between genotypic differences of IL-6 gene and serum levels of IL-6, soluble IL-6 receptor (sIL6-R), soluble gp130 (sgp130), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were investigated. There were no differences in the allelic distribution of the IL-6 gene C allele between MS patients and healthy controls, and no association of the IL-6 gene C allele with serum levels of IL-6, sIL-6R, spg130, sICAM and sVCAM-1 was found.

Adolescent↗
PubMed2000

Response-related fMRI analysis during encoding and retrieval revealed differences in cerebral activation by retrieval success.

The aim of the study was to identify cerebral activation associated with sufficient or insufficient encoding, and with correct or false recognition. Fourteen volunteers performed two paradigms: explicit learning of words; and later retrieval of previously presented words. Items were classified according to the subjects' recognition performance. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during encoding and retrieval. Response-related fMRI-analysis was used to compare activation associated with the subjects' retrieval success. During encoding, there was a trend towards increased activation of the left medial cingulate gyrus and of the right fusiform gyrus for later hits (correctly identified, learned target words) in comparison with misses (non-identified targets). During recognition, signal intensities associated with false alarms (falsely identified distractors) were significantly higher in left and right extrastriate cortex than those associated with hits, misses and correct rejections of distractors. Activation in the anterior cingulate gyrus during retrieval was related to reaction time and might be associated with the preparation or performance of motor response. Increased activation during false alarms might reflect a source-monitoring deficit or an increased subjective familiarity with distractors that have been most intensively processed in extrastriate visual cortex.

Adult↗
PubMed2000

Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD.

BACKGROUND: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. OBJECTIVE: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. METHODS: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. RESULTS: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. CONCLUSION: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

Aged↗
PubMed2000

Allelic association between the D10S1423 marker and Alzheimer's disease in a German population.

Recently a full genome survey detected an allelic association between Alzheimer's disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the telomere). In this study we examined the D10S1423 marker in an ethnically homogeneous German population of 80 AD patients and two groups of controls, 168 healthy subjects and 149 depressed patients. The 234-bp allele of the D10S1423 marker showed a significant association with AD (P = 0.033). In conclusion, our results support that the D10S1423 marker is associated with an increased AD risk and provides further evidence for an AD susceptibility locus on chromosome 10.

Aged↗
PubMed2000

Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease.

The conversion of brain cholesterol into 24S-hydroxycholesterol and its subsequent release into the periphery is probably an important step for the maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma 24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increased brain cholesterol turnover during neurodegeneration. We investigated whether plasma 24S-hydroxycholesterol concentrations depend on the severity of AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance of the apoE4 allele may be associated with increased apoE-mediated transport of brain cholesterol to the periphery or with decreased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD.

Aged↗
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

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Age of Onset↗
PubMed2000

Distinction of early- and late-onset depression in the elderly by their lifetime symptomatology.

OBJECTIVE: It has been proposed that early-onset depression (EOD) and late-onset depression (LOD) differ etiologically and phenomenologically. To validate the phenomenological distinction, the affective symptoms of elderly subjects with EOD and LOD were compared. METHODS: Seventy-one patients with age-at-onset of depression below 60 years (EOD) and 67 age-matched patients with age-at-onset above 60 years (LOD) were consecutively recruited from the Departments of Psychiatry of the University of Mainz and the University of Bonn. To reduce the effect of interepisode variance of symptoms, we focused on the lifetime prevalence of different affective symptoms which were evaluated using the Composite International Diagnostic Interview (CIDI). Logistic regression analysis was performed to identify particular depressive symptoms which might discriminate EOD and LOD, and to account for possible sociodemographic differences between the two groups. RESULTS AND CONCLUSION: Low spirits and feelings of worthlessness were more frequently found in EOD, they were sufficient discriminators to distinguish elderly subjects with EOD and LOD. This study provides further evidence for a phenomenological distinction between early- and late-onset depression in the elderly.

Affect↗
PubMed2000

The concreteness effect: evidence for dual coding and context availability.

The term concreteness effect refers to the observation that concrete nouns are processed faster and more accurately than abstract nouns in a variety of cognitive tasks. Two models have been proposed to explain the neuronal basis of the concreteness effect. The dual-coding theory attributes the advantage to the access of a right hemisphere image based system in addition to a verbal system by concrete words. The context availability theory argues that concrete words activate a broader contextual verbal support, which results in faster processing, but do not access a distinct image based system. We used event-related fMRI to detect the brain regions that subserve to the concreteness effect. We found greater activation in the lower right and left parietal lobes, in the left inferior frontal lobe and in the precuneus during encoding of concrete compared to abstract nouns. This makes a single exclusive theory unlikely and rather suggests a combination of both models. Superior encoding of concrete words in the present study may result from (1) greater verbal context resources reflected by the activation of left parietal and frontal associative areas, and (2) the additional activation of a non-verbal, perhaps spatial imagery-based system, in the right parietal lobe.

Adult↗
PubMed2000

Subthreshold depressive and anxiety disorders in the elderly.

The aims of the present study were to compare the current and lifetime prevalences for major and subthreshold affective disorders in elderly subjects in the general population, to assess the influence of demographic variables on prevalence rates, and to examine co-morbidity between these disorders. Major and subthreshold disorders were diagnosed in 286 subjects (aged >/= 60 years). Four-point-nine percent of the subjects had a lifetime diagnosis of major depression, 31.8% either minor or recurrent brief depression, 6.6% a major anxiety disorder, and 18.5% a subthreshold anxiety disorder. The risk for current and lifetime subthreshold anxiety was higher in females than in males, the lifetime prevalence for subthreshold anxiety disorders was increased in elderly subjects and subjects with low professional levels. Increased co-morbidity between major and subthreshold depressive and anxiety disorders could not be observed. In the elderly, subthreshold depressive and anxiety disorders are frequent, more so than major affective disorders. The presence of subthreshold anxiety disorders, but not subthreshold depression, is influenced by age, gender, and previous professional level. Further research focusing on detection, evaluation of risk factors and the relevance for the quality of life in the elderly general population is needed.

Aged↗
PubMed2000

Interindividual variation of cerebral activation during encoding and retrieval of words.

The aim of the present study was to compare the cerebral activation associated with encoding and retrieval in individual subjects with the average activation in the same group of subjects. Twelve volunteers performed two paradigms: 1) intentional encoding of words, and 2) recognition of learned words intermixed with new distracters. Echo-planar magnetic resonance imaging (MRI) of BOLD signal changes was used to compare cerebral activation between active and resting conditions. During encoding, activation of the left precentral gyrus related to the motor response was observed in some subjects. Averaged data showed increased activation of the left precentral gyrus, the supplementary motor area (SMA), the left inferior frontal gyrus and in the left temporo-occipital junction. During recognition, motor response-related activity was found in the precentral cortex and SMA in most subjects. Activation in other brain areas showed considerable interindividual variation. In the entire group, recognition showed activation of the left dorsolateral prefrontal cortex, the precentral gyrus, the SMA, and the temporo-occipital junction. The total amount and the distribution of task-related cerebral activation varies considerably between individuals and might correspond to individual preferences of cognitive strategies. The investigation of these interindividual variations will be an exciting scientific challenge in the near future.

Adult↗
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

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

No association between an intronic biallelic polymorphism of the FE65 gene and Alzheimer's disease.

The cleavage of the amyloid precursor protein (APP) into amyloidogenic components (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). FE65 is a protein that is involved in APP metabolism and may facilitate the production of Abeta. Recently, an intronic polymorphism of the gene encoding FE65 (FE65) was associated with altered risk for the development of sporadic AD. In our sample of 102 AD patients and 351 non-demented controls we did not replicate the association between FE65 and AD. Moreover, we observed no risk-modifying interaction and no linkage disequilibrium between FE65 and the gene encoding the acid protease cathepsin D (catD), which - like FE65 - is involved in APP metabolism and is also located on chromosome 11p15. We conclude that, whereas FE65 is implicated in AD pathology, the gene encoding FE65 does not appear to confer a substantial risk for AD.

Aged↗