Biomedical subjects

M Weisbrod

Publications and source records attributed to M Weisbrod.

At least 19 recordsLinked to original sources

PubMed2006

Pergolide as adjuvant therapy to amisulpride in the treatment of negative and depressive symptoms in schizophrenia.

Negative and cognitive symptoms of schizophrenia are associated with a hypodopaminergic state in the frontal cortex and do not respond to neuroleptics equally well as positive symptoms. Therefore pharmacological strategies, which increase dopamine metabolism in the mesocortical pathways, may prove beneficial to ameliorate these symptoms. We report on a case of a patient with paranoid schizophrenia, who still presented negative and depressive symptoms during treatment with amisulpride for more than 6 weeks. We prescribed pergolide (a mixed D1/D2 agonist) as adjuvant therapy to treat these symptoms. The patient showed an improvement of global psychopathology, decrease of negative and depressive symptoms, while no changes in positive symptoms nor EPS were present. For this patient, the adjuvant therapy of pergolide to amisulpride constituted a valid pharmacological approach to treat negative and depressive symptoms of schizophrenia, without increasing positive symptoms.

Adult↗

PubMed2005

[Executive control functions and neuropsychiatric disorders -- perspectives for research und clinical practice].

Executive control functions are higher cognitive functions for complex goal-oriented behavior in situations where routine mechanisms are not available or inappropriate. In clinical practice executive dysfunction presents with deficits in cognitive function as well as social behavior and drive. Executive control functions rely on intact networks involving prefrontal cortex and subcortical structures, which can be modulated by monoaminergic neurotransmitters. Deficits of executive control have been described in a variety of neuropsychiatric disorders. We present a review of the findings with a focus on movement disorders, schizophrenia and affective disorders. We emphasize similarities between these disorders regarding the pathophysiology of fronto-subcortical networks. Based on these similarities, principles of pharmacological and rehabilitative strategies can be applied to the treatment of executive deficits in a variety of neuropsychiatric disorders without being specific for one disease. Since executive dysfunction is highly relevant to prognosis, controlled trials of these treatments are urgently needed.

Basal Ganglia Diseases↗

PubMed2005

Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine.

Evidence for a disturbed maturation of information processing in migraine came recently from evoked and event-related potential studies during childhood. In adult migraineurs, deficient habituation is proposed as principal interictal abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This study investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of N180 latency from pre- to postpubertal age reflects maturation and was clearly present in controls but lessened in migraineurs. N180 latency was prolonged in migraineurs without aura from 12 years onwards. Habituation did not differ between groups. In conclusion, diminished N180 latency reduction with age in migraineurs gives further evidence that maturation of visual information processing is altered in migraine. Deficient habituation to pattern-reversal VEPs could not be confirmed during childhood migraine.

Adolescent↗

PubMed2004

Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset.

Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode.

Adolescent↗

PubMed2004

Nongenetic pathologic developments of brain-wave patterns in monozygotic twins discordant and concordant for schizophrenia.

Evidence from previous studies has suggested that the inter-individual differences in human brain-wave patterns (EEG) are predominantly determined by genetic factors. In particular, the within-pair EEG concordance of monozygotic (mz) twins was found to be typically as high as r = 0.81 across channels and frequency bands, thus being comparable to that between repeated assessments on the same individual with typically r = 0.83. Yet our investigations into mz twins discordant and concordant for schizophrenia yielded a significantly reduced within-pair EEG concordance for both, the pairs discordant for schizophrenia and the pairs concordant for schizophrenia (with concordance for schizophrenia assessed through a syndrome-oriented approach). A multivariate discriminant function of EEG parameters distinguished in a reproducible way between affected and unaffected subjects at an overall performance of >75% correctly classified subjects, while the severity of illness, as derived from EEG-differences between affected and unaffected subjects, was closely related to the severity of illness as provided by psychopathology syndrome scores. Consequently, EEG anomalies associated with schizophrenia and manifested differently in the mz co-twins concordant for schizophrenia are likely the effect of nongenetic, pathologic processes that evolved independently in the co-twins' genetically identical brains once the illness began to progress. The existence of such nongenetic processes would suggest a modification of the standard phenotype-to-genotype search strategies of molecular-genetic studies that aim to link the schizophrenia phenotype to genetic vulnerability factors.

Adult↗

PubMed2004

Ethnicity-independent genetic basis of functional psychoses: a genotype-to-phenotype approach.

The functional psychoses schizophrenia, schizoaffective disorder, and bipolar illness represent complex clinical syndromes that are characterized by phenotypic heterogeneity. Yet evidence from numerous studies suggests that (1) the prevalence of schizophrenia and bipolar illness is with 1% very similar across ethnicities, and (2) a strong genetic component is involved in the disorders' pathogenesis. Using data from different US-American ethnicities (77 families with a total of 17 unaffected and 170 affected sib pairs; 276 marker loci), we searched for ethnicity-independent oligogenic susceptibility loci for which the between-sib genetic similarity in affected sib pairs deviated from the expected values. Specifically, we addressed the question of the extent to which genetic risk factors and their interactions constitute multigenic inheritance of functional psychoses across populations and might constitute universal targets for treatment. Our novel multivariate genotype-to-phenotype search strategy was based on a genetic similarity function that allowed us to quantify the inter-individual genetic distances d(x(i), x(j)) between the allelic genotype patterns x(i), x(j) of any two subjects i, j with respect to n loci l(1), l(2), em leader l(n). Thus, we were able to assess the between-ethnicity, the within-ethnicity, and the within-family genetic similarities. The problem of ethnicity-independent vulnerability was addressed by treating the Afro-American families as "training" samples, while the non-Afro-American families served as independent "test" samples. We evaluated the between-sib similarities, which were expected to deviate from "0.5" in affected sib pairs if the region of interest contained markers close to vulnerability genes. The reference value "0.5" was derived from the parent-offspring similarities that are always 0.5, irrespective of the affection status of parents and offspring. We found 12 vulnerability loci on chromosomes 1, 4, 5, 6, 13, 14, 18, and 20, that were reproducible across the two samples under comparison and therefore, likely to constitute an ethnicity-independent, oligogenic vulnerability model of functional psychoses. The elevated vulnerability appeared to be unspecific and to act in such a way that exogenous factors become more likely to trigger the onset of psychiatric illnesses.

Algorithms↗

PubMed2004

[The PreFord Study. A prospective cohort study to evaluate the risk of a cardiovascular event (overall-collective) as well as a prospective, randomized, controlled, multicentre clinical intervention study (high-risk-collective) on primary prevention of cardiovascular diseases in the Ford Motor Company employees in Germany].

The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40,000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores, 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases, 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by, 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation, occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and evidence based treatment. Group III: high risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into two interventional groups. The first one, the intervention-group "PreFord" will perform an occupational integrated rehabilitation program (2,5-3 hours twice a week, for 15 weeks according to the BAR guidelines) with a following engagement in heart-groups and an annual repetition of the check-ups. The second group, the "classic" intervention-group will be treated evidence based in cooperation with their GP. As a result of this long term interventional study efficient, area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated. Core elements will be exercise- and lifestyle-oriented concepts as well as guideline-based pharmacotherapy.

Adult↗

PubMed2004

[Neuropsychological equivalences and therapeutic consequences of the dynamic structural model].

Firstly the core concepts of the dynamic structural model and the methods from which the model was developed will be discussed. These core concepts include concepts of personality structure and affect dynamic, of dynamic affective derailment with dissociation of individual element structures, the capacity of disactualisation of unwanted mental content, and autopraxis as the basis of memory renewals, which are formed and channelled through selection. Furthermore we will consider the dependence of memory function on texturing, development of coherence, affective freighting and repetition of usage in Janzarik's system. Neuropsychological counterparts are to be found in experimental studies on filter, gating and control functions, in studies on automatic vs. controlled processes, the central executive and executive control function. Autopraxis and priming operations will be related to each other. Furthermore, the connection of neuronal plasticity to a raised signal-to-noise ratio and the relationship to extinction of delusional content through broadening of new fields of experience will be discussed. In a summary of the frappant parallels of experimental and clinical viewpoints of Janzarik's model we will show the therapeutic perspective and the psychotherapeutically important integration of the lifeworld of the patient with experimentally investigated neuropsychological functions through Janzarik's conceptualisation.

Humans↗

PubMed2003

[Niemann-Pick disease type C--a neurometabolic disease through disturbed intracellular lipid transport].

Niemann-Pick disease type C (NPC) is a rare, neurovisceral lipid storage disorder caused by genetic defects in lipid transporting proteins. It is distinct from Niemann-Pick types A and B (sphingomyelin lipidoses) and displays genetic (mutations in the NPC1 or NPC2[=HE1] gene), biochemical, and clinical heterogeneity. Late infantile to juvenile forms of NPC predominate and are characterised by atypical behaviour, ataxia, dysarthria, dysphagia, dystonia, cataplexy, vertical gaze palsy, splenomegaly, and dementia. In adult variants, psychosis and dementia are common, and dysarthria, ataxia, splenomegaly, and vertical gaze palsy are further facultative signs. Routine laboratory results including serum cholesterol are normal. In bone marrow smears, sea-blue histiocytes are often demonstrated and foam cells sometimes seen. The diagnosis is confirmed by detecting free cholesterol accumulation in perinuclear granules (lysosomes) and reduced cholesterol esterification after challenge with exogenous low-density lipoprotein in fibroblasts. Alternatively or additionally, mutational analysis can be performed. Treatment is restricted to symptomatic measures, since there is no specific therapy.

Adult↗

PubMed2003

Emotional and behavioural problems in children and adolescents with primary headache.

Psychiatric co-morbidity is an important risk factor for chronification of primary headache into adulthood. The aim of this study was to investigate the extent and clinical relevance of emotional and behavioural problems in children and adolescents with primary headache. Children and adolescents (n = 128) with primary headache (International Headache Society, codes 1.1, 1.2, 2.1) and 83 matched controls aged 6-18 years were examined by standardized dimensional psychometric tests (Child Behaviour Checklist, Depression Inventory for Children and Adolescents, Anxiety Questionnaire for Pupils). Children and adolescents with primary headache suffer more often from internalizing problems (depression, anxiety, somatization) than healthy controls. The detected emotional and behavioural problems are clinically relevant and require particular therapy in every third child suffering from headache. Two out of three children and adolescents with primary headache do not show clinically relevant psychopathology and may benefit from minimal therapeutic intervention. One of three examined headache patients needs additional psychiatric therapy.

Adolescent↗

PubMed2002

Arithmetic fact retrieval and working memory in schizophrenia.

Despite its importance in every-day life and vocational rehabilitation, arithmetic ability has rarely been investigated in schizophrenic patients. Those few studies reporting arithmetic deficits in schizophrenia, however, administered complex calculation tasks which drew not only on arithmetic abilities, but also on working memory resources known to be impaired in schizophrenia. In the present study, arithmetic abilities and working memory functions were investigated in schizophrenic patients (n=24) and healthy control subjects (n=24). Arithmetic fact retrieval was assessed in single-digit multiplication and corresponding division problems using a result verification task which minimized working memory demands. Problem size and the disparity of the proposed result were manipulated. The storage component of working memory was tested with a digit span forward task and the executive control component with a digit span backward as well as with verbal fluency tasks. Schizophrenic patients performed worse than controls only in the executive tasks. Digit span forward was preserved. In the arithmetic tasks, groups did not differ from each other, and a similar pattern of task manipulations was obtained. Hence, despite the executive control deficit retrieval of arithmetic facts is preserved in schizophrenia. Moreover, the same underlying cognitive processes as in control subjects are involved.

Adult↗

PubMed2002

Lack of age-dependent development of the contingent negative variation (CNV) in migraine children?

Increased negativity of contingent negative variation (CNV) in adult migraineurs is thought to reflect cortical hyperexcitability. CNV amplitude changes with age in healthy adults. Recently, evidence emerged that this might not be the case for migraineurs. Our study investigates age-dependency of CNV during childhood age. Seventy-six healthy controls and 61 children with migraine without aura (IHS code 1.1) between 6 and 18 years were examined using an acoustic S1-S2-CNV-paradigm with a 3-s inter-stimulus interval. The amplitude of the late component of CNV, as well as total CNV at the vertex (Cz according to the international 10-20 system), were significantly higher in migraineurs without aura than in controls. Healthy controls showed increasing amplitudes of CNV with age, whereas in migraine children without aura amplitudes did not change. Thus group differences were reduced during adolescence. Increased CNV negativity might reflect a biological vulnerability to migraine, rather than being a result of chronification. Migraineurs seem to lack age-dependent development of CNV also during early age, which supports the hypothesis of migraine as a maturation disorder.

Adolescent↗

PubMed2001

Is frontal lobe involved in the generation of auditory evoked P50?

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.

Acoustic Stimulation↗

PubMed2001

[HIV patients with psychiatric illnesses. Treatment strategies and drug interactions].

Since the beginning of the endemic phase of the human immunodeficiency virus (HIV), about 60,000 humans have been infected in Germany by this retrovirus. Epidemiological data indicate approximately 2,500 new infections annually. Due to the multiagent antiviral therapy available, only about 600 cases progressed to the clinical picture of full-blown acquired immunodeficiency syndrome (AIDS) in 1999. [Robert-Koch-Institut (Berlin), http://www.rki.de] If an HIV infection or AIDS is current, a higher prevalence of psychiatric disorders in these persons can be anticipated. Psychoactive drugs and their dosages need to be chosen under several considerations and with regard to the HIV infection, since interactions between antiviral and psychotropic drugs occur frequently. The use of psychotropic drugs is often required and thus cannot be ignored. Therefore, psychiatric disorders, medical treatment strategies, interactions between psychotropic and antiretroviral drugs, and biotransformation mechanisms are discussed with regard to an underlying HIV infection.

Anti-HIV Agents↗

PubMed2001

[Similarity of the brains of twins].

PURPOSE: To test the assumption underlying every morphometric twin study that the brains of monozygotic twins are almost identical. METHODS: High resolution MRI of the neurocranium of 26 monozygotic twin pairs were acquired and the volumes of 36 cerebral structures were measured. The same twins served as control group after rear-ranging them into non-related pairs of same sex and matching them for age, body height and body weight. RESULTS: For most of the examined structures the correlations within the twins were significant (R = 0.97-0.59). Except for total forebrain volume the controls showed no significant similarity. CONCLUSIONS: For almost every measured cerebral structure the assumption, that significant similarities exist between healthy monozygotic twins is correct. Therefore discordant monozygotic twins represent an excellent sample when investigating cerebral correlates of neurologic and psychiatric disorders.

Adult↗

PubMed2000

Schizophrenia and smoking: evidence for a common neurobiological basis?

Several previous investigations have suggested that the gene for the alpha 7-nicotinic receptor may play a role in the pathogenesis of schizophrenia and may be responsible for the heavy smoking among schizophrenic patients. In a study of 129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients we have aimed 1) to confirm the potential association between schizophrenia and the alpha 7-nicotinic receptor, 2) to test the diagnostic specificity of alpha 7-receptor subunits with respect to psychiatric diagnoses, and 3) to investigate potential receptor differences between smokers and nonsmokers in the general population. Our analysis included the two dinucleotide polymorphisms D15S1360 and L76630 that are localized in a genomic fragment containing the alpha 7-nicotinic receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the allele distributions of patients and controls were detected for these two markers with all three diagnostic subgroups contributing to the discrimination. An independently ascertained replication sample of 24 patients confirmed this finding. Our results suggested an unspecific vulnerability that depended on the severity of overall psychopathology in terms of the co-occurrence of psychopathology with no clear-cut boundary between the diagnostic entities. In comparison with healthy controls, this vulnerability was lowest among schizophrenics, intermediate among bipolars, and highest among schizoaffectives. As to the question of alpha 7-receptor differences between smokers and nonsmokers among the healthy control subjects, our analysis revealed no significant differences, thus indicating that the differences between patients and controls are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:173-177, 2000.

Bungarotoxins↗

PubMed2000

Executive control is disturbed in schizophrenia: evidence from event-related potentials in a Go/NoGo task.

BACKGROUND: Schizophrenic patients suffer from cognitive and attentional deficits, particularly from failure of executive control functions. METHODS: This study investigated the cortical organization of executive control in schizophrenic patients and healthy control subjects using event-related potentials (ERPs). Event-related potentials were collected while subjects performed an auditory Go/NoGo task that required response inhibition. To exclude stimulus discriminability and early stimulus processing to confound results, stimuli were adjusted to the subject's individual discrimination ability and were presented in a simple and a difficult version. RESULTS: Schizophrenic patients performed similar to control subjects in the Go condition but worse than control subjects in the NoGo condition that required response inhibition. Event-related potentials revealed the neurophysiological substrate of this dysfunction. In the Go conditions, both healthy control subjects and schizophrenic patients showed the same voltage pattern. In the NoGo condition, control subjects and patients showed similar cortical activation only during early processing (N2 time window). However, in later stages of processing (P3 time window), healthy subjects showed left lateralization of ERPs over frontal areas while schizophrenic patients did not. CONCLUSIONS: We conclude that schizophrenic patients exhibit deficient processing in a neuronal network, including left frontal areas, that is involved in later stages of executive control function.

Adult↗

PubMed2000

Genetic influence on laterality in schizophrenia? A twin study of neurological soft signs.

OBJECTIVE: This study explored the genetic basis of neurological soft signs in schizophrenia and addressed disturbed hemispheric lateralization. METHOD: The authors investigated neurological soft signs in 30 monozygotic twin pairs, 13 pairs discordant for schizophrenia or schizoaffective disorder and 17 healthy comparison twin pairs. RESULTS: The twins with schizophrenia showed higher total scores for neurological soft signs than did the comparison subjects. The total scores for neurological soft signs of the nonaffected discordant twins were significantly higher than those of the comparison twins. There was a significant difference between the nonaffected and affected discordant twins in total scores for neurological soft signs. In contrast to the comparison subjects, the nonaffected and affected twins of the discordant pairs showed a trend toward higher scores for neurological soft signs on the left body half. CONCLUSIONS: These results suggest that the occurrence of neurological soft signs and, more specifically, their lateralization to the left body half are genetically transmitted.

Adult↗