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Matthias J Müller

Publications and source records attributed to Matthias J Müller.

At least 19 recordsLinked to original sources
PubMed2007

The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression.

This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the MAOA gene, at least in female patients. An independent replication of our finding is needed. If replicated, genotyping of this locus could become a promising tool to predict response to mirtazapine treatment in females suffering from major depression.

Adult↗
PubMed2006

Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI.

Hippocampus atrophy is a frequent finding in mild cognitive impairment (MCI), whereas diffusion-tensor-imaging (DTI) has demonstrated its value to detect subtle brain tissue changes in several neuropsychiatric diseases including MCI. To compare the diagnostic accuracy of both methods, high resolution MRI scans for hippocampus volumetry, and co-registered DTI-scans for ROI-based mean diffusivity (MD) and fractional anisotropy (FA) were carried out in 18 patients with amnestic MCI (7 females, age 67.3+/-8.7 years, MMSE 25.2+/-2.2) and 18 controls (age 66.9+/-9.0 years, MMSE 28.7+/-1.0). Diagnostic properties of normalized hippocampus volume (HV) and DTI measures with regard to MCI status were estimated by receiver operating characteristics (ROC) analyses and logistic regression. Parameters of the left hippocampus showed superior predictive power when compared to the right. At a specificity set to 80%, left HV had low sensitivity (50%); left hippocampal MD values revealed superior sensitivity (89%), similar to left hippocampal FA (78%). The results demonstrate higher sensitivity of DTI-derived left hippocampal parameters than volume measures in detecting subtle hippocampal abnormalities related to MCI.

Aged↗
PubMed2006

Predicting conversion to dementia in mild cognitive impairment by volumetric and diffusivity measurements of the hippocampus.

In our prospective study of diffusion tensor imaging (DTI), we measured hippocampal mean diffusivity (MD) and volumes in amnestic mild cognitive impairment (MCI). Thirteen MCI patients were followed-up by clinical assessment over a mean 112-year period. MCI patients who converted to dementia (6 of 13) during the observation period had slightly elevated left hippocampal mean diffusivity at baseline compared with MCI patients who remained clinically stable. Hippocampal volumes as well as baseline verbal memory and MMSE did not differ significantly between stable MCI patients and converters. Hippocampal diffusivity was superior to hippocampal volumes for prediction of conversion to dementia in MCI patients during a 112-year period.

Aged↗
PubMed2006

Pattern of microstructural brain tissue alterations in Fabry disease: a diffusion-tensor imaging study.

Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. To quantify brain structural changes in clinically affected male and female patients with FD we performed a prospective Diffusion-Tensor Imaging (DTI) study in 27 adult Fabry patients (13m, 14f) and 21 age-matched controls (12 m, 9f). Global Mean Diffusivity (MD) was increased in FD (P = 0.003) whereas global Fractional Anisotropy (FA) did not differ significantly between FD and controls. Even FD patients without significant WMLs (9m, 9f) showed increased global MD (P = 0.004). Regions of interest with significant MD elevations were located in the frontal, parietal and temporal white matter. No differences of thalamic and hippocampal DTI measurements could be detected between FD and controls. DTI parameters did not differ between male and female patients. The data provide the first evidence of a pattern of marked structural brain tissue alterations in adult FD male and female patients even without WMLs. DTI seems to be an appropriate diagnostic tool to quantify brain tissue integrity in FD. Moreover, this method could be favorable for longitudinal assessment of brain structure alterations in FD, and for monitoring the cerebral effects of enzyme replacement therapy.

Adult↗
PubMed2006

Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers after acute haloperidol challenge.

In animal studies, acute antipsychotic treatment was shown to enhance striatal DOPA-decarboxylase (DDC) activity. However, this phenomenon has not been demonstrated in humans by positron emission tomography (PET). Therefore, we investigated acute haloperidol effects on DDC activity in humans using [18F]fluorodopa (FDOPA) PET. Nine healthy volunteers were scanned with FDOPA in drug-free baseline conditions and after 3 days of haloperidol treatment (5 mg/day). A continuous performance test (CPT) was administered in both conditions. The net blood-brain clearance of FDOPA (K(in)app) in striatum, mesencephalon, and medial prefrontal cortex was calculated by volume-of-interest analysis. The macroparameter K(in)app is a composite of several kinetic terms defining the distribution volume of FDOPA in brain (V(e)D) and the relative activity of DOPA decarboxylase (k3D). Therefore, compartmental kinetic analysis was used to identify the physiological basis of the observed changes in K(in)app period. The magnitude of K(in)app was significantly increased in the putamen (18%) and mesencephalon (36%). Furthermore, V(e)D in the brain was increased by 15%. Increments of k3(D) in the basal ganglia did not attain statistical significance. The significant worsening of CPT results did not correlate with changes in FDOPA utilization. The present PET results indicate potentiation of FDOPA utilization in human basal ganglia by acute haloperidol treatment, apparently due to increased availability throughout the brain. The stimulation of DDC cannot be excluded due to insufficient statistical power in the estimation of k3(D) changes.

Adult↗
PubMed2006

CNS manifestations of Fabry's disease.

BACKGROUND: Fabry's disease is a rare hereditary lysosomal storage disease with multiorgan involvement. Deficiency of alpha-galactosidase A activity leads to accumulation of neutral glycosphingolipids, especially in vascular endothelial and smooth-muscle cells. Along with progressive renal and cardiac dysfunction, stroke is a major and often life-threatening burden of the disease. Cerebral vasculopathy, confirmed by neuropathological, neuroradiological, and functional studies, occurs commonly and leads to ischaemic cerebrovascular events at an early age. RECENT DEVELOPMENTS: Fabry's disease is an X-linked disease and women have been regarded as only mildly affected carriers. However, research has shown a high prevalence of ischaemic stroke and transient ischaemic attacks, along with imaging evidence of CNS involvement, in female patients with the disease, which suggests that at least in a subgroup of clinically affected women the severity of CNS disease is comparable to that in men. Another study has shown a high prevalence of the disease in young patients of both sexes with cryptogenic stroke, emphasising the need for more clinical attention to be paid to this under-diagnosed disease. WHERE NEXT?: These new findings should be replicated in larger samples. Brain structural changes and CNS involvement in the disease need to be monitored carefully in follow-up studies to broaden our knowledge of the course of neurobiological changes and to identify potential effects of enzyme-replacement therapy, which is already showing some benefit in cardiac and renal dysfunction in the disease. Finally, a diagnosis of Fabry's disease should always be considered in young patients who have had a stroke.

Brain↗
PubMed2006

Detection of depression in acute schizophrenia: sensitivity and specificity of 2 standard observer rating scales.

OBJECTIVE: To compare the psychometric properties of the Calgary Depression Rating Scale (CDRS) and the Hamilton Depression Rating Scale (HDRS) for severity assessment of depression in acute schizophrenia. METHOD: During clinical routine treatment, we investigated 119 inpatients with acute schizophrenia, using the CDRS, the HDRS, and a global 4-point Depression Severity Scale (DEP-SEV). We compared CDRS and HDRS sum scores regarding their diagnostic accuracy, with global severity of depression as the criterion. We estimated sensitivity and specificity on the basis of receiver operating characteristic curves. RESULTS: According to global clinical ratings (DEP-SEV), 31% of patients had no depression, 19% had mild, 31% had moderate, and 19% had severe depression. Sensitivity was significantly higher (P < 0.05) for the CDRS than for the HDRS to assess mild (0.94 vs 0.76, cut-off 3 vs 10 points) or severe depression (1.00 vs 0.78, cut-off 11 vs 22 points); specificity was comparably high (> or = 0.88) for both scales. CONCLUSION: Despite the fact that both scales were effective in separating mild, moderate, and severe depression, significant advantages emerged for the CDRS to detect mild or severe depression in schizophrenia.

Acute Disease↗
PubMed2005

Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia.

Amisulpride is a clinically effective antipsychotic drug in a broad dose range with low propensity for extrapyramidal symptoms (EPS). Daily doses and plasma levels of amisulpride were analyzed within a large-scale therapeutic drug monitoring (TDM) survey to find plasma level ranges for optimized treatment under naturalistic conditions. Data of 378 schizophrenic patients treated with amisulpride (100-1550 mg) were included (40% female). Amisulpride plasma levels were analyzed at steady state; assessment comprised improvement (CGI-I) and side-effects, particularly EPS. For detection of cut-off values regarding non-response or EPS, receiver operating characteristics (ROC) curves were applied and the area under the ROC curve (AUC) was calculated. Amisulpride daily doses (594+/-262 mg) and plasma levels (315+/-277 ng/ml) were significantly correlated (r=0.53; P<0.0001). Patients with non-response to amisulpride (8.9%) had significantly (P<0.05) lower plasma levels (248+/-291 ng/ml) than patients with at least moderate improvement (316+/-253 ng/ml) despite comparable amisulpride doses (628+/-253 vs. 590+/-263 mg). Patients with EPS (14.6%) had significantly (P<0.05) higher amisulpride plasma levels (377+/-290 ng/ml) than patients without EPS (305+/-274 ng/ml) despite similar doses in both groups (595+/-266 vs. 594+/-246 mg). ROC analyses revealed significant predictive properties of amisulpride plasma levels (P<0.05) for non-response (AUC=0.65+/-0.05) and EPS (AUC=0.62+/-0.05), respectively. Daily amisulpride doses did not significantly predict non-response or EPS. Optimal amisulpride plasma level values to avoid non-response and EPS were 100 or 320 ng/ml, respectively. Analysis of clinical utility revealed that blood levels must be analyzed in 7 patients until one patient benefits from the TDM procedure by avoiding non-response or EPS. Although our results were mainly explorative, TDM of amisulpride seems very useful for clinical decision making.

Adolescent↗
PubMed2005

Nocturnal hormone profiles in patients with schizophrenia treated with olanzapine.

Nocturnal hormone profiles were measured in patients with schizophrenia with predominantly negative symptoms both under drug-free baseline conditions and after subchronic administration of the atypical antipsychotic olanzapine, with the aim of characterizing its pharmacological properties on the neuroendocrine level. The following hormones were studied in the sleep laboratory under polysomnographic control: adrenocorticotrophic hormone, cortisol, growth hormone (GH), prolactin, testosterone, and melatonin. Blood samples were taken at regular time intervals over the night, and serum concentrations of the hormones were determined. Ten patients completed the study, two of them were excluded from analysis due to incomplete hormone profiles. The dynamics of baseline nocturnal hormone secretion were similar to the patterns known from healthy subjects. After the treatment period of about 4 weeks, hypothalamic-pituitary-adrenal axis activity was reduced with decreased cortisol plasma levels compared to baseline conditions. Olanzapine induced a moderate prolactin elevation. The characteristic GH peak around sleep onset, clearly present under baseline conditions, was markedly reduced after treatment. Testosterone and melatonin secretion were not significantly altered. In conclusion, although interpretation is difficult in some cases due to interference with indirect effects of olanzapine administration and the consequences of the clinical course of the underlying schizophrenic disorder, the neuroendocrine findings are consistent with the receptor-binding profile of olanzapine where, beside the D(2) antagonism, the antiserotonergic properties are most important.

Adrenocorticotropic Hormone↗
PubMed2005

Functional implications of hippocampal volume and diffusivity in mild cognitive impairment.

Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was significantly lower (-11%, P = 0.02) in MCI patients than in control subjects. No significant differences were found for the right hippocampus (-4%). Mean diffusivity (MD) was significantly elevated in MCI patients vs. controls in left (+10%, P = 0.002) and right hippocampal areas (+13%, P = 0.02). Hippocampal volume and MD values were not significantly correlated. Combining left hippocampal volume and MD measures showed that lower left hippocampal volumes were associated with poor verbal memory performance particularly when co-occurring with high MD values. No comparable associations could be found regarding the right hippocampal formation and with respect to non-verbal memory function. The results demonstrate that microstructural abnormalities as revealed by DTI are very sensitive early indicators of hippocampal dysfunction. The combination of macro- and microstructural parameters in hippocampal areas could be promising in early detection of neurodegenerative processes.

Aged↗
PubMed2005

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment.

Different processes like microvascular dysfunction, free radical toxicity, beta-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impairment (MCI), 25 patients with Alzheimer's dementia (DAT), and 21 age-matched controls. Additionally, DTI values were correlated with memory performance in the delayed verbal recall test. Fractional anisotropy and mean diffusivity differed significantly between MCI and controls, as well as between DAT and controls. Performance in the delayed verbal recall test of the entire study group correlated significantly with posterior cingulate bundle anisotropy and diffusivity. Using ccDTI seems, hence, a favorable strategy to detect and quantify the structural integrity of posterior cingulate white matter in MCI. Alterations of DTI parameters substantiate the involvement of white matter pathology in the development of MCI. Moreover, ccDTI could serve as in vivo method to investigate age and disease-related myelin alterations as potential morphological substrates of cognitive dysfunction.

Aged↗
PubMed2005

Sequentially adjusted randomization to force balance in controlled trials with unknown prevalence of covariates: application to alcoholism research.

AIMS: In treatment outcome studies with small to medium sample sizes (n < 200), the balance of groups with regard to important factors, which sometimes occur at low prevalence, is indispensable for adequate interpretation. This study tested a method for use in clinical alcoholism research, an uncomplicated procedure for satisfactory randomization of patients to different treatments, taking into account relevant background variables. METHODS: An easily applicable modification of Efron's biased coin method for the randomization of treatments within strata of unknown but low prevalence was compared with the original approach and alternative methods by computer simulation (10,000 runs). An application example for a clinical trial in alcoholism research is given. RESULTS: The sequentially adjusted randomization procedure revealed results similar to Efron's approach without the necessity for monitoring the assignment history throughout the trial. The new method was slightly superior to Efron's approach in randomizing subjects in strata with n < or = 20, whereas strata with n > 20 favoured randomization with Efron's approach. Taking into account all results from simulation, the new approach reached a proportion of acceptable balanced randomization > 95% in all stratum sizes. CONCLUSIONS: The approach, a special case of the standard urn design, provides three major advantages in clinical trials: (i) it can be easily implemented in any trial without technical equipment; (ii) it works with high accuracy in trials with a priori unknown but low numbers of subjects (4 < or = n < or = 20) in prognostic relevant strata; and (iii) a deterministic assignment tendency is completely avoided, as a random process takes place throughout the assignment procedure. The modified biased coin method can be recommended as one possible strategy for special purposes, particularly in alcoholism research.

Alcoholism↗
PubMed2005

The Calgary Depression Rating Scale for schizophrenia in a healthy control group: psychometric properties and reference values.

BACKGROUND: Assessment of depression in schizophrenia is of great importance as depressive signs and symptoms and suicidality are highly prevalent in patients with schizophrenic disorders. The Calgary Depression Rating Scale (CDSS) is the standard assessment instrument for that purpose due to its proven reliability and validity. However, so far no reference values derived from an adequate healthy sample have been published. METHODS: The present study analyzed CDSS item scores and summary scores in 154 healthy subjects (49% female, mean age 32.8+/-11.7 years) selected from studies as controls for schizophrenic patients. RESULTS: The total CDSS score was 2.6+/-2.7 (range 0-12), about 1/3 of healthy subjects had scores=0. Gender differences were observed with respect to "early awakening" and "suicidal ideation" with higher scores in females. Total CDSS scores (r=-0.17, P=0.03) and single items were slightly negatively correlated with age. The psychometric properties of the CDSS scale were satisfying (corrected item-score correlations r(tc)=0.33-0.61, internal consistency Cronbach's alpha=0.76, one-dimensional factor structure). CDSS total scores showed a skewed distribution fitting the upper part of a normal distribution. Based on the empirical distribution of CDSS values, reference values were listed for the total group of healthy subjects, and for females and males separately. CONCLUSIONS: The results corroborate the favourable psychometric properties of the CDSS found previously in clinical samples in a healthy control group. The reference values reported here can assist the clinical use and interpretation of CDSS values and emphasize the usefulness of the CDSS for a thorough assessment of depression and suicidality in schizophrenia.

Adult↗
PubMed2004

Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages. METHODS: We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and age-matched control subjects. RESULTS: Alzheimer-typical patterns of cerebral glucose metabolism were significantly related to elevated phosphorylated tau levels (p =.009) but not to elevated total tau levels. In six of seven mild cognitive impairment patients with increased phosphorylated tau concentrations, Alzheimer disease-typical positron emission tomography patterns were found. Phosphorylated tau measurement separated patients with and without Alzheimer disease-typical positron emission tomography findings with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: Unlike total tau levels, elevated phosphorylated tau levels were strictly related to Alzheimer-typical patterns of cerebral glucose metabolism in mild cognitive impairment patients. The results can be interpreted as validation of phosphorylated tau measurements for detecting Alzheimer disease in mild cognitive impairment patients.

Aged↗
PubMed2004

Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study.

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.

Aged↗
PubMed2004

Heart rate variability during sleep in patients with schizophrenia treated with olanzapine.

Cardiac adverse events in patients treated with atypical antipsychotics have gained increasing interest in recent years. In the present study, heart rate variability (HRV), which is a sensitive parameter reflecting central autonomic cardiac control, was investigated during treatment with olanzapine. Ten physically healthy male patients with schizophrenia, who displayed predominantly negative symptoms, were studied in the sleep laboratory under drug-free baseline conditions and after 4 weeks of olanzapine medication. HRV was assessed during different sleep stages both in the time and frequency domains. Only slight changes in HRV were shown during treatment, and appeared to be independent of sleep stages. Spectral analysis indicated a slight shift of the sympathovagal balance in favour of the sympathetic tone, which was consistent with an elevation of heart rate in the time domain; total HRV was not altered. These changes are in accordance with olanzapine's receptor profile exerting anticholinergic and anti-adrenergic properties. In conclusion, taken together with findings from previous studies demonstrating that olanzapine does not cause clinically significant changes of the QTc interval, the present results are consistent with the known cardiac safety profile of olanzapine.

Adolescent↗