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Georg Winterer

Publications and source records attributed to Georg Winterer.

32 records · Page 2Linked to original sources
PubMed2003

Association of the G1947A COMT (Val(108/158)Met) gene polymorphism with prefrontal P300 during information processing.

BACKGROUND: A common functional polymorphism, G1947A, of the catechol-O-methyltransferase (COMT) enzyme has gained interest in schizophrenia research because of its critical involvement in cortical dopamine catabolism and frontal lobe function. An assumed mechanism of dopamine is the reduction of noise in prefrontal neural networks during information processing. Therefore, the hypothesis was tested whether a variation of the COMT genotype is associated with prefrontal noise, which is in part reflected by the frontal P300 amplitude. It was predicted that homozygous Met allele carriers have a lower frontal P300 amplitude. METHODS: The P300 component (auditory oddball) was recorded in 49 schizophrenic patients and 170 healthy control subjects. Three single nucleotide polymorphisms (SNPs) of the COMT gene (G1947A, C1883G, and G1243A) were investigated. RESULTS: We observed a significant effect of G1947A COMT genotype on frontal P300 amplitude, with evidence for a genotype x diagnosis interaction. Lower frontal P300 amplitudes occurred in homozygous carriers of the Met allele, particularly in schizophrenic patients. CONCLUSIONS: The association of the frontal P300 amplitude with the G1947A COMT genotype further emphasizes the functional role of this SNP. As the finding was mainly observed in schizophrenic patients, this may indicate that additional factors are required to interact with COMT genotype to affect prefrontal function. The smaller frontal P300 amplitude in Met carriers suggests that the amount of noise in prefrontal neural networks during information processing might be in part under genetic control, which is mediated by dopamine.

Acoustic Stimulation↗
PubMed2003

P300 and genetic risk for schizophrenia.

BACKGROUND: We assessed the suitability of event-related potential frontal and temporoparietal P300 changes as intermediate phenotypes in genetic studies of schizophrenia. We applied a principal component analysis approach based on the notion that P300 abnormalities in siblings of schizophrenic patients may involve a widespread network of relatively weak cortical generators and because an earlier, smaller study that used a topographic analysis of covariance model did not show that localized P300 changes predict risk for schizophrenia. METHODS: P300 changes in 66 schizophrenic patients, 115 healthy siblings of schizophrenic patients, and 89 unrelated controls were studied during a standard auditory oddball paradigm. Principal components were calculated across electrodes, revealing frontal and temporoparietal components for latency and amplitude, respectively. For the frontal and temporoparietal P300 amplitude and latency components, the intraclass correlations (ICCs) between sib-pairs (pairs of unaffected siblings and schizophrenic index patients) and the relative risk ratios (lambda) were determined. RESULTS: Compared with controls, schizophrenic patients and their unaffected siblings showed significant reductions in the temporoparietal P300 amplitude component. Both groups were also characterized by a significantly higher frontal P300 amplitude component. Significant ICCs and increased relative risk ratios were found for the frontal (ICCU = 0.18; P =.04; lambda = 3.4) and temporoparietal (ICCU = 0.24; P =.01; lambda = 1.7) P300 amplitude components. CONCLUSIONS: Temporoparietal P300 amplitude reduction and frontal P300 amplitude increase seem to be quantitative phenotypes associated with increased risk of schizophrenia. Both measures may be useful for increasing the statistical power of genetic studies of schizophrenia.

Adolescent↗
PubMed2003

Association of EEG coherence and an exonic GABA(B)R1 gene polymorphism.

The GABA(B) receptor 1 gene is mapped to chromosome 6p21.3 within the HLA class I region close to the HLA-F gene. Susceptibility loci for epilepsy and schizophrenia have been mapped in this region. Based on pharmacological evidence, it has been suggested that GABA(B) receptors may play a crucial role in the synchronization of EEG oscillations, which in turn can be abnormal in neuropsychiatric disorders. In the present study, the hypothesis was tested, whether three exonic variants of the gene encoding the human GABA(B) receptor (GABA(B)R1) modify cortical synchronization measured as scalp-recorded EEG-coherence. Two principal components of EEG coherence (frontal coherence, parietotemporal coherence) were investigated in 104 healthy subjects during three conditions: resting EEG, activated EEG, and event-related EEG. No significant associations were found between the frontal coherence component and any polymorphism or between the parietotemporal coherence component and the exon 1a1 polymorphism. However, parietotemporal coherence showed statistically highly significant associations across all three experimental conditions with exon 7 and trend associations with exon 11. The results provide evidence that the translated polymorphism of exon 7 may be functionally meaningful and impact cortical EEG oscillations. Since variations of EEG coherence have been described for several neuropsychiatric disorders, the present association should be tested in clinical samples using EEG coherence as an intermediate phenotype.

Adult↗
PubMed2003

Genetics of human prefrontal function.

Evolution of the prefrontal cortex was an essential precursor to civilization. During the past decade, it became increasingly obvious that human prefrontal function is under substantial genetic control. In particular, heritability studies of frontal lobe-related neuropsychological function, electrophysiology and neuroimaging have greatly improved our insight. Moreover, the first genes that are relevant for prefrontal function such as catechol-O-methyltransferase (COMT) are currently discovered. In this review, we summarize the present knowledge on the genetics of human prefrontal function. For historical reasons, we discuss the genetics of prefrontal function within the broader concept of general cognitive ability (intelligence). Special emphasis is also given to methodological concerns that need to be addressed when conducting research on the genetics of prefrontal function in humans.

Brain Chemistry↗
PubMed2003

The relationship between reaction time, error rate and anterior cingulate cortex activity.

Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short (n=19) vs. long reaction times (n=17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the N1 component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions.

Acoustic Stimulation↗
PubMed2003

Association analysis of exonic variants of the GABA(B)-receptor gene and alpha electroencephalogram voltage in normal subjects and alcohol-dependent patients.

Based on pharmacologic evidence, it has been suggested that GABA(B) receptors may play a crucial role in the generation of alpha-electroencephalogram (EEG) oscillations. We tested whether three exonic variants of the gene encoding the human GABA(B) receptor (GABA(B)R1) modify scalp-recorded alpha-EEG voltage. One hundred twenty-eight patients suffering from alcoholism and 114 normal subjects were investigated. Alcohol-dependent patients were included because evidence exists that the frequently observed alpha low voltage in these subjects is at least partly a trait variable. Logistic regression analyses revealed no associations between alpha-EEG voltage and polymorphic variations in exon 1a1 or exon 11. A significant interaction was observed for an exon 7 substitution polymorphism and diagnosis (P = 0.009). Post hoc analyses showed an association between EEG phenotype and exon 7 genotype in normal subjects only. It is concluded that this particular association may only be observable under physiologic conditions and that alpha low voltage in alcohol-dependent subjects is under the control of either different genes or that it is related to the disease process.

Adult↗
PubMed2002

Cortical hypoactivation during resting EEG in schizophrenics but not in depressives and schizotypal subjects as revealed by low resolution electromagnetic tomography (LORETA).

This study was performed in order to address the question whether the newly introduced technique of low-resolution electromagnetic tomography (LORETA) is able to detect hypofrontality in schizophrenic patients. We investigated resting EEGs of 19 unmedicated schizophrenics and 20 normal subjects. For comparison, we also investigated 19 subjects with schizotypal personality and 30 unmedicated depressive patients. A significant increase of delta activity was found in schizophrenic patients over the whole cortex, most strongly in the anterior cingulate gyrus and temporal lobe (fusiform gyrus). Both schizotypal subjects and depressive subjects showed significantly less delta, theta and beta activity in the anterior cingulum, a decrease of alpha1 activity in the right temporal lobe and a decrease of alpha2 activity in the left temporal lobe. The results suggest general cortical hypoactivation, most pronounced in the anterior cingulate and temporal lobe in schizophrenics, whereas there is evidence for a complex, frequency-dependent spatial pattern of hyperactivation in schizotypal subjects and depressive patients. The results are discussed within a neurophysiological and methodological framework.

Adult↗
PubMed2002

Evidence for the importance of the human dopamine transporter gene for withdrawal symptomatology of alcoholics in a German population.

Two new polymorphisms in the 3' untranslated region (3'UTR) of the dopamine transporter (DAT1) gene, adjacent to the known variable number of tandem repeats (VNTR) polymorphism, have been investigated in the present population-based association study including 351 alcoholics and 336 controls. The DraI restriction site was not polymorphic in our population. The G2319A polymorphism was not significantly different with respect to genotype or allele distribution between alcoholics and controls. Subsequently, in individuals with VNTR homozygosity for the ten repeat allele, we found a higher prevalence of A/A homozygosity in patients with seizure history (P = 0.001, odds ratio (OR) = 7.913), with delirium history (P = 0.032, OR = 4.707), and with an alcoholic mother (P = 0.021, OR = 5.250), compared to homozygote 10/10 controls. Our findings provide further evidence that the 3'UTR of the DAT1 gene affects vulnerability to severe alcohol withdrawal.

Adult↗
PubMed2002

Preliminary experience with an ampakine (CX516) as a single agent for the treatment of schizophrenia: a case series.

We used L-(quinoxalin-6-ylcarbonyl)piperidine (CX516) (a modulator of the alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA) receptor) as a sole agent in a double blind placebo-controlled design in a small series of patients with schizophrenia who were partially refractory to treatment with traditional neuroleptics. The study entailed weekly increments in doses of CX516, from 300 mg tid for week 1 up to 900 mg tid on week 4. Patients were followed with clinical ratings, neuropsychological testing, and were monitored for adverse events. Four patients received 2 to 4 weeks of CX516, two received placebo and two withdrew during the placebo phase. Adverse events associated with drug administration were transient and included leukopenia in one patient and elevation in liver enzymes in another. No clear improvement in psychosis or in cognition was observed over the course of the study. CX516 at the doses tested did not appear to yield dramatic effects as a sole agent, but inference from this study is limited.

Adult↗
PubMed2002

Allelic variants of the functional promoter polymorphism of the human serotonin transporter gene is associated with auditory cortical stimulus processing.

The loudness dependence (LD) of the auditory-evoked N1/P2 component has been shown to be related to the central serotonergic neurotransmission. Allelic variants in the promoter region of the 5-hydroxytryptamine transporter (5-HTT) gene were shown to modulate serotonergic activity. It was hypothesized that the three genotypes (l/l, s/l, s/s) differ with respect to LD. Allelic variants of the 5-HTT promoter region and LD at the Cz electrode were determined in 185 healthy subjects prospectively. A significant association was found between LD and genotype (ANOVA: F=4.172, p=0.017). Individuals homozygous for the l allele exhibited a weaker LD compared to heterozygous subjects. The results are consistent with the reported association between 5-HTT genotype and serotonin transport capacity in lymphoblasts, and indicate that auditory stimulus processing is associated with genetic variants of the brain serotonergic system. The LD may serve as endophenotype in human serotonin research.

Adult↗
PubMed2002

Frontal and temporal dysfunction of auditory stimulus processing in schizophrenia.

Attention deficits have been consistently described in schizophrenia. Functional neuroimaging and electrophysiological studies have focused on anterior cingulate cortex (ACC) dysfunction as a possible mediator. However, recent basic research has suggested that the effect of attention is also observed as a relative amplification of activity in modality-associated cortical areas. In the present study, the question was addressed whether an amplification deficit is seen in the auditory cortex of schizophrenic patients during an attention-requiring choice reaction task. Twenty-one drug-free schizophrenic patients and 21 age- and sex-matched healthy controls were studied (32-channel EEG). The underlying generators of the event-related N1 component were separated in neuroanatomic space using a minimum-norm (LORETA) and a multiple dipole (BESA) approach. Both methods revealed activation in the primary auditory cortex (peak latency approximately 100 ms) and in the area of the ACC (peak latency approximately 130 ms). In addition, the adapted multiple dipole model also showed a temporal-radial source activation in nonprimary auditory areas (peak latency approximately 140 ms). In schizophrenic patients, significant activation deficits were found in the ACC as well as in the left nonprimary auditory areas that differentially correlated with negative and positive symptoms. The results suggest that (1) the source in the nonprimary auditory cortex is detected only with a multiple dipole approach and (2) that the N1 generators in the ACC and in the nonprimary auditory cortex are dysfunctional in schizophrenia. This would be in line with the notion that attention deficits in schizophrenia involve an extended cortical network.

Acoustic Stimulation↗
PubMed2002

Volition to action--an event-related fMRI study.

Current concepts of the anterior cingulate cortex (ACC) increasingly emphasize its role as an interface between limbic and neocortical functions. It has been pointed out that ACC activation reflects the intentional amount of effort (volition) that a subject uses in a task. In previous electrophysiological source localization investigations during a choice reaction task, we described a strong early activation in the ACC region approximately 120-150 ms after stimulus presentation. The degree of midline ACC activation correlated negatively with reaction time. This observation together with the finding that ACC activation precedes information processing in cortical association areas provided preliminary support to the notion that the extent of ACC activation is related to a subject's task engagement. However, due to the inverse problem and the relatively low spatial resolution of the electrophysiological measurements, we were not able to make inferences about the validity and the exact localization of the observed midline activation maximum. We addressed this question and performed an event-related fMRI study in six healthy volunteers during a visual choice reaction task. Two checkerboard stimuli were presented either in the left or right visual hemifield in randomized order and with an interstimulus interval requiring an appropriate motor response (left-right button press). A bilateral BOLD maximum was observed in the region of the supplementary motor area confluent with the neighboring motor area of the dorsal ACC. The degree of ACC activation correlated significantly with reaction time. These results are in line with our previous electrophysiological findings and provide further evidence that early ACC activation during a choice reaction task reflects the intentional effort of a subject to carry out a task.

Adult↗
PubMedDate not supplied

Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

AIMS: To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. METHODS: Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. RESULTS: Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. CONCLUSION: Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

Adult↗