Biomedical subjects

E M Meisenzahl

Publications and source records attributed to E M Meisenzahl.

At least 19 recordsLinked to original sources

PubMed2006

Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation.

BACKGROUND: Working memory as a part of higher-order executive functions is defined by the parallel storage and processing of information. Recent functional fMRI studies have revealed a functional, interregional disintegration of a neuronal network connecting cortical, subcortical and cerebellar regions in schizophrenic patients (SZ). Cognitive impairment in working memory is a core psychopathological correlate of schizophrenic symptoms. Atypical neuroleptics such as quetiapine have shown good efficacy in treating positive and negative symptoms. The presented study evaluated the impact of a neuroleptic steady state treatment with quetiapine on the altered working memory activation patterns in schizophrenia. METHODS: Patients were examined by fMRI at baseline and after 12 weeks of steady state treatment with quetiapine. Matched healthy controls (HC) underwent baseline examination. In the scanner, stimuli were presented in a 2-back and 0-back condition of a working memory (wm) paradigm, whereby a degraded and a non-degraded version were used each time. Additionally, behavioural responses (reaction time to target stimuli and error ratio) were measured. RESULTS: At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance. CONCLUSIONS: The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

Adult↗

PubMed2006

Plexin B3 is genetically associated with verbal performance and white matter volume in human brain.

The presence of genetic influences on cognitive performance and brain volume is well established. However, specific genetic determinants of the variance of these quantitative traits are not yet known. Plexins act as receptors for semaphorins and are implicated in axon guidance, which is a key process in brain development. We have previously shown that plexin B3 is a highly potent stimulator of neurite outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits related to human brain development and cerebral connectivity. We identified several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D and V1596E) conserved at the corresponding positions of the orthologs in mouse and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male patients with schizophrenia. Cognitive performance was measured with the vocabulary test (Wortschatztest (WST)), a method to estimate roughly general intelligence (g). Brain morphology was characterized by magnetic resonance imaging. Compared to subjects not carrying the modern, human-specific haplotype A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis (P=0.0004). This effect could be observed in three independent groups (healthy males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037). Additionally, the haplotype A was associated with increased volume of brain white matter that in turn correlated with performance in the vocabulary test. These findings suggest that plexin B3 may influence cognitive performance, and the development of white matter in vivo in a way similar to its known stimulating effect on neurite outgrowth in vitro. These novel observations warrant further replication in independent samples.

Adult↗

PubMed2005

Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients.

OBJECTIVE: Supposing a "hyperdopaminergic State" associated at least with acute psychotic illness phases in schizophrenia, a direct relationship between striatal dopamine metabolism and the core psychopathological symptoms rarely can be provided. Recently, a new SPECT ligand to the presynaptic dopamine transporter (DAT) was introduced. Association of DAT availability and the acute psychotic syndrome is now demonstrated in a large cohort of first episode, never treated schizophrenic patients. METHODS: Twenty-eight inpatients suffering from a first acute exacerbation of schizophrenia and 12 healthy control subjects underwent SPECT scanning with the new radioligand [(99m)Tc]TRODAT-1. On the day of SPECT, psychopathology was assessed using specific scales including PANSS. RESULTS: There was no significant difference in [(99m)Tc]TRODAT-1 specific binding to the striatal DAT comparing both groups. The extend of hallucinations was significantly inversely correlated with DAT availability in patients with a predominantly positive syndrome type. DISCUSSION: Our data support evidence that differences in presynaptic dopaminergic activity in schizophrenic patients are associated with the extend of the acute psychotic syndrome. [(99m)Tc]TRODAT-1 seems to be a useful agent for in vivo assessment of a psychopathological association with dopamine metabolism.

Acute Disease↗

PubMed2005

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.

Adult↗

PubMed2005

The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1.

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a striatal 'hyperdopaminergic state', presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photon-emission-tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECT-ligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia.

Acute Disease↗

PubMed2004

[Value of diagnostic imaging in evaluation of electroconvulsive therapy].

Magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) may be able to investigate the clinical efficacy and underlying neuronal processes of electroconvulsive therapy (ECT). The following review focuses on neuroimaging in ECT. Neuroimaging findings support that ECT does not result in significant macroscopic structural changes. However, in patients with subtle structural changes such as subcortical lesions and dilatation of lateral ventricles before ECT, the possibilities of poor therapeutic outcome, increased incidence of delirium, and longer-lasting cognitive deficits should be considered. Functional studies show reduced blood flow and glucose metabolism during the first days after ECT. Afterwards, their normalization can be observed, which seems to correlate to clinical improvement. The importance of this suppression effect needs to be further elucidated. Future studies of receptor systems and longitudinal studies will open new perspectives in future imaging research.

Brain↗

PubMed2002

Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients.

Twin studies point toward a substantial heritability in individual variations in the size of the human brain. However, the etiology is largely unknown. The prion protein (gene name: PRNP) aids cellular resistance to oxidative stress and neurodegeneration and is involved in neurodevelopment. This study examines the influence of a polymorphism in the PRNP gene on brain morphology in 47 healthy males and 43 male schizophrenic patients. All subjects underwent identical MRI scanning sessions followed by segmentation in cerebrospinal fluid (CSF), gray and white matter tissue, and genotyping for a biallelic polymorphism in PRNP (Met129Val). Genotype and allele frequencies did not differ between schizophrenic patients and controls but the polymorphism was associated with white matter tissue reduction (P = 0.024) and enlargement of CSF compartments (P = 0.039). These findings suggest that homozygosity for methionine at codon 129 is associated with decreased white matter tissue and larger CSF volume in right-handed male healthy volunteers and schizophrenic patients. This, however, being a novel finding, should warrant further investigation.

Adolescent↗

PubMed2002

Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine.

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).

Adult↗

PubMed2001

In-vivo analysis of the human planum temporale (PT): does the definition of PT borders influence the results with regard to cerebral asymmetry and correlation with handedness?

The aim of our study was to examine whether the degree of planum temporale (PT) asymmetry and the possible correlation of morphological PT asymmetries with handedness are influenced by the definition of PT borders. For this reason, we applied three different anatomical PT definitions formerly used in the literature. The PT total (with the end of the Sylvian fissure (SF) as its posterior border) was separated into anterior and posterior regions. The border between anterior and posterior PT was set according to the following definitions: at the end of Heschl's gyrus (1st definition); at the start of the ascending SF ramus according to the 'knife-cut' method (2nd definition); and at the bifurcation of the SF (3rd definition). Thirty right-handed healthy men were recruited. MRI data sets analyzed with the software program BRAINS were used for in vivo PT volumetry. The Edinburgh Handedness Inventory (EHI) and the Hand Dominance Test were used to determine the degree of handedness. In summary, we detected that the type and the degree of asymmetry between left and right PT were strongly dependent on the definition used for PT borders: a left>right asymmetry was found in all PT regions, except a right>left asymmetry of the anterior PT according to our 1st PT definition (lateral to Heschl's gyrus) and a symmetry of the posterior PT according to our 3rd PT definition (posterior to SF bifurcation). In addition, a significant correlation was found between the degree of handedness measured by the EHI and the right posterior PT (3rd definition). We conclude that the influence of the definition of PT borders on the investigated variables may explain some of the variances between former investigations on PT asymmetry and handedness. The possible implications of the correlation between handedness and the extension of the right parietal PT are discussed and have to be elucidated by further studies.

Adolescent↗

PubMed2001

Corpus callosum and P300 in schizophrenia.

Functional abnormalities in the interhemispheric transfer via the corpus callosum in schizophrenia may result in filtering problems and information processing problems, which may in turn be related to the synchronization of cortical event-related activity. To explore whether a relationship exists between corpus callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late auditory event-related P300 potentials, 50 patients with schizophrenia as well as 50 healthy controls were examined. The absolute CC size and subregional areas, as well as the CC areas adjusted for total brain volume, were not significantly different between patients with schizophrenia and controls. While no significant group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies, P3a- and PSW-latencies were significantly prolonged for patients with schizophrenia. Absolute CC total size was significantly correlated with P3b-amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia, significant correlations were observed between the subregion of the posterior body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW-latencies were not significantly correlated to CC size in either patients with schizophrenia or healthy controls. The results are discussed in terms of the possibility that abnormalities in interhemispheric transfer may underlie the mechanisms of schizophrenia.

Adult↗

PubMed2001

The effect of the skull on event-related P300.

OBJECTIVES: Event-related potentials (EP) indicate neuronal processes with a high temporal resolution, while functional magnetic resonance imaging (fMRI) has a high spatial distribution. Information from both techniques may complement each other. However, this combination is fraught with difficulty because of a possible interference of the skull or the scalp with scalp-recorded EP. The aim of the present study was to investigate this influence of skull and scalp thicknesses on event-related P300 potentials. METHODS: Thirty healthy controls were examined using an auditory evoked P300 elicited by a standard oddball paradigm. Skull and scalp thicknesses were determined using coronal T2-weighted magnetic resonance imaging (MRI). RESULTS: P3b-amplitudes were significantly correlated with temporo-parietal skull thickness (r=-0.42; P=0.021; regression slope of -1.14 microV/mm skull thickness), whereas scalp had no influence on P300. The amplitude of the more frontal subcomponent P3a was not related to frontal skull thickness. CONCLUSIONS: Therefore, the utility of P300 as a research tool can be enhanced when adjustment for skull thickness is made.

Adult↗

PubMed2001

Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia.

OBJECTIVE: This study investigated the effect on brain morphology of an interleukin-1beta genetic polymorphism (C-->T transition at position -511) in patients with schizophrenia. METHOD: In vivo magnetic resonance imaging and genotype analysis were used in the examination of 44 male schizophrenic patients and 48 healthy male comparison subjects. RESULTS: No association between the interleukin-1beta polymorphism and schizophrenia was detected. Within the patient group, bifrontal-temporal gray matter volume deficits and generalized white matter tissue deficits in allele 2 carriers (genotype T/T or C/T) were found. In contrast, the interleukin-1beta polymorphism had no influence on brain morphology within the healthy subjects. CONCLUSIONS: The data suggest that allele 2 within the promoter region of the interleukin-1beta gene at position -511 contributes to structural brain alterations in patients with schizophrenia.

Adolescent↗

PubMed2001

Functional magnetic resonance imaging research in psychiatry.

Advanced functional imaging techniques now make it possible to study in vivo the relationship between altered cerebral activation patterns and the psychopathologic and cognitive features of psychiatric disorders. Functional MR imaging (fMRI) offers new approaches to research questions in psychiatry that could not have been addressed earlier by positron emission tomography and single photon emission CT. Basic features of the biology of psychiatric disorders now can be elucidated by means of fMRI. Study designs involving fMRI capitalize on the technique's enhanced spatial and temporal resolution, noninvasive nature, and absence of radiation exposure.

Arousal↗

PubMed2000

Digitized analysis of abnormal hand-motor performance in schizophrenic patients.

Many studies have shown a high prevalence of discrete neuromotor disturbances in schizophrenic patients. It was hypothesized that these disturbances are lateralized and reflect a neurodevelopmental disorder underlying schizophrenia. A new method for assessing subtle motor dysfunction and hemispheric asymmetries is the registration of hand movements with a digitizing tablet. Using this method, we studied hand-motor dysfunction and its lateralization in schizophrenics, as compared with healthy controls. All subjects (27 schizophrenic patients, 13 of them without neuroleptic medication, the others under neuroleptics; 31 healthy controls) drew super-imposed concentric circles. We computed kinematic parameters reflecting velocity and automatization to quantify neurological soft signs (NSS). The patients had significant impairments of regularity of repetitive hand movements, as compared with the healthy controls (F> or =5.35; p< or =0.024(*)). Comparing differences of left- and right-hand performance between patients and controls, we found longer stroke duration (F=(15,98); p=0.000***) and decreased automatization (F=18,14; p=0.000***), especially on the left side in schizophrenic patients. Measuring hand movements with a digitizing tablet is a sensitive method for assessing subtle motor dysfunction in schizophrenic patients, not reflected in the scores of clinical scales. Our findings show NSS in schizophrenic patients, independently of neuroleptics. Further, the hypothesis of lateralization of cerebral structures generating NSS towards the right hemisphere in schizophrenia is supported.

Adult↗

PubMed2000

Adhesio interthalamica in male patients with schizophrenia.

OBJECTIVE: The authors investigated whether absence of the adhesio interthalamica in patients with schizophrenia constitutes a marker of early developmental neuropathological changes. METHOD: Thirty male patients with schizophrenia and 30 healthy male subjects were recruited for study. Magnetic resonance imaging was performed, and the presence or absence of the adhesio interthalamica was determined for each subject. The length and volume of the third ventricle were also measured. RESULTS: No differences in the presence or absence of the adhesio interthalamica were found between patients with schizophrenia and normal comparison subjects. Patients without the adhesio interthalamica had significantly higher scores for negative symptoms than patients with the adhesio interthalamica. There was no correlation between absence of the adhesio interthalamica and length and volume of the third ventricle in either patients or comparison subjects. CONCLUSIONS: The findings suggest that patients with schizophrenia who do not have the adhesio interthalamica are characterized by more severe negative symptoms.

Adolescent↗

PubMed2000

D2 receptor occupancy under recommended and high doses of olanzapine: an iodine-123-iodobenzamide SPECT study.

The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose-response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine.

Adult↗

PubMed1999

P300 subcomponents reflect different aspects of psychopathology in schizophrenia.

BACKGROUND: The aim of the study was to investigate abnormalities of P300 subcomponents in schizophrenic patients as well as relationships between these subcomponents and positive versus negative schizophrenic symptoms. METHODS: Nineteen schizophrenic patients and 19 healthy controls were tested with an auditory event-related potential oddball paradigm designed to elicit the P300. The P300 data were analyzed by separating P300 subcomponents with a recently developed dipole source model. RESULTS: Compared to healthy controls, schizophrenic patients showed reduced P300 amplitudes of the temporo-basal dipoles, corresponding mainly to P3b. Positive symptoms of the Positive and Negative Syndrome Scale correlated positively with the temporo-basal but not with temporo-superior dipole P300 activities, whereas negative symptoms correlated positively with the temporo-superior but not with temporo-basal dipole activities. CONCLUSIONS: The P300 subcomponents separated with the dipole model are affected in a different manner by positive versus negative symptoms. Furthermore, the positive correlation between the severity of psychopathology and the P300 amplitudes of the different dipole activities appears to be a state-dependent effect, which has to be separated from the P300 amplitude reduction as a trait marker in schizophrenic patients.

Adult↗

PubMed1999

[Dysmorphophobia--symptom or diagnosis?].

Dysmorphophobia as a new psychiatric syndrome was described by the Italian psychiatrist Morselli in 1891. Dysmorphophobic symptoms are associated with several other psychiatric disorders. The term of dysmorphophobia will be discussed along a theoretical review. We present the case of a 20-year-old patient with dysmorphophobic symptoms. In the scope of ICD 10, DSM-III-R/DSM IV diagnostical criteria we outline problems of the diagnostical classification of dysmorphophobic signs.

Adult↗