Biomedical subjects

Benno Pütz

Publications and source records attributed to Benno Pütz.

5 recordsLinked to original sources

PubMed2006

Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome.

Restless legs syndrome (RLS; MIM 102300) is a common neurological disorder characterized by dysesthesias and an urge to move the lower limbs. The symptoms predominantly occur at rest, in the evening, and improve with movement. There is a high familial aggregation but gene mutations have not yet been found. Three loci for RLS on chromosomes 12q, 14q, and 9p (RLS-1, RLS-2, and RLS-3) have been reported with a recessive (RLS-1) and autosomal dominant (RLS-2, RLS-3) mode of inheritance, respectively. The overall contribution of these loci to this disorder is not known. To evaluate the significance of these loci, we investigated 12 RLS families for possible linkage to these chromosomal regions. Genotyping was carried out in 70 affected family members using 26 polymorphic microsatellite markers (chromosome 12: 7; chromosome 14: 7, chromosome 9: 12). Linkage analysis was carried out using the published parameters applied in the original studies (chromosome 12: q=0.25, f0=0.005, f1=0.005, f2=0.8; chromosome 14: q=0.003, f0=0.005, f1=f2=0.95; chromosome 9: q=0.001, f0=0.005, f1=f2=0.95; affected individuals only). In addition, transmission disequilibrium test (TDT) analyses were done. We found evidence for linkage on chromosome 12 using the TDT. Linkage to RLS-2 and RLS-3 was excluded in 1 of 12 families. This supports the existence of RLS-1 and provides evidence for the likelihood of further genetic locus heterogeneity of RLS. Investigations in additional RLS families are required to confirm the known loci and further genome wide linkage analyses have the potential to identify additional RLS loci.

Adolescent↗

PubMed2005

Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety.

For >15 generations, CD1 mice have been selectively and bidirectionally bred for either high-anxiety-related behavior (HAB-M) or low-anxiety-related behavior (LAB-M) on the elevated plus-maze. Independent of gender, HAB-M were more anxious than LAB-M animals in a variety of additional tests, including those reflecting risk assessment behaviors and ultrasound vocalization, with unselected CD1 "normal" control (NAB-M) and cross-mated (CM-M) mice displaying intermediate behavioral scores in most cases. Furthermore, in both the forced-swim and tail-suspension tests, LAB-M animals showed lower scores of immobility than did HAB-M and NAB-M animals, indicative of a reduced depression-like behavior. Using proteomic and microarray analyses, glyoxalase-I was identified as a protein marker, which is consistently expressed to a higher extent in LAB-M than in HAB-M mice in several brain areas. The same phenotype-dependent difference was found in red blood cells with NAB-M and CM-M animals showing intermediate expression profiles of glyoxalase-I. Additional studies will examine whether glyoxalase-I has an impact beyond that of a biomarker to predict the genetic predisposition to anxiety- and depression-like behavior.

Analysis of Variance↗

PubMed2004

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Adult↗

PubMed2003

Assessing brain activity through spatial Bayesian variable selection.

Statistical parametric mapping (SPM), relying on the general linear model and classical hypothesis testing, is a benchmark tool for assessing human brain activity using data from fMRI experiments. Friston et al. discuss some limitations of this frequentist approach and point out promising Bayesian perspectives. In particular, a Bayesian formulation allows explicit modeling and estimation of activation probabilities. In this study, we directly address this issue and develop a new regression based approach using spatial Bayesian variable selection. Our method has several advantages. First, spatial correlation is directly modeled for activation probabilities and indirectly for activation amplitudes. As a consequence, there is no need for spatial adjustment in a postprocessing step. Second, anatomical prior information, such as the distribution of grey matter or expert knowledge, can be included as part of the model. Third, the method has superior edge-preservation properties as well as being fast to compute. When applied to data from a simple visual experiment, the results demonstrate improved sensitivity for detecting activated cortical areas and for better preserving details of activated structures.

Adult↗

PubMedDate not supplied

Role of subvoxel free fluid on diffusion parameters in brain tissue with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and its correlation with physical disability: histogram analysis of standard and fluid-attenuated MR diffusion.

BACKGROUND AND PURPOSE: Subcortical signal intensity abnormalities and lacunar infarcts are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. MR diffusion studies reveal abnormalities in lesions and also within normal appearing white matter. To further characterize the underlying pathologic abnormality, we evaluated the role of subvoxel free fluid in brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy on diffusion parameters and physical disability and analyzed the interrelation between diffusion variables and nonlacunar T2 lesion load. METHODS: Mean diffusivity maps from fluid-attenuated and standard diffusion images of 13 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and seven age-matched control participants were compared by means of histogram analysis for three tissue compartments (whole brain parenchyma, normal appearing brain tissue, and nonlacunar lesions) by using a semiautomated region growing algorithm to define whole brain parenchyma and lesions on fluid-attenuated images. RESULTS: In both patients and control participants, the average mean diffusivity of whole brain parenchyma was lower on fluid-attenuated than on standard images (P <.001). Average mean diffusivity and peak location for all compartments were significantly elevated in patients (P <.001) and higher for lesions than for normal appearing brain tissue on both types of images (P <.001). The difference between standard and fluid-attenuated average mean diffusivity of normal appearing brain tissue, reflecting the subvoxel free fluid content, was elevated in patients (P <.05) and correlated closely with the Rankin score (Spearman's rank correlation coefficient = 0.889, P <.001). Average mean diffusivity of whole brain parenchyma and normal appearing brain tissue correlated strongly with the nonlacunar T2 lesion load (Pearson's correlation coefficient = 0.743-0.928, P <.005). CONCLUSION: This study shows that standard diffusion measurements are contaminated by free fluid partial volume effects for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and for control participants. It also provides evidence of a clinical significance of increased subvoxel free fluid in normal appearing brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which may be more important than either global atrophy, increased diffusivity or, T2 lesion load.

Adult↗