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D Umbricht

Publications and source records attributed to D Umbricht.

16 recordsLinked to original sources
PubMed2006

Impaired attentional modulation of auditory evoked potentials in N-methyl-D-aspartate NR1 hypomorphic mice.

In human neurophysiology, auditory event-related potentials (AEPs) are used to investigate cognitive processes such as selective attention. Selective attention to specific tones causes a negative enhancement of AEPs known as processing negativity (PN), which is reduced in patients with schizophrenia. The evidence suggests that impaired selective attention in these patients may partially depend on deficient N-methyl-D-aspartate receptor (NMDAR)-mediated signaling. The goal of this study was to corroborate the involvement of the NMDAR in selective attention using a mouse model. To this end, we first investigated the presence of PN-like activity in C57BL/6J mice by recording AEPs during a fear-conditioning paradigm. Two alternating trains of tones, differing in stimulus duration, were presented on 7 subsequent days. One group received a mild foot shock delivered within the presentation of one train (conditioning train) on days 3-5 (conditioning days), while controls were never shocked. The fear-conditioned group (n= 9) indeed showed a PN-like activity during conditioning days manifested as a significant positive enhancement in the AEPs to the stimuli in the conditioning train that was not observed in the controls. The same paradigm was then applied to mice with reduced expression of the NMDAR1 (NR1) subunit and to a wild-type control group (each group n= 6). The NR1 mutants showed an associative AEP enhancement, but its magnitude was significantly reduced as compared with the magnitude in wild-type mice. We conclude that electrophysiological manifestations of selective attention are observable yet of different polarity in mice and that they require intact NMDAR-mediated signaling. Thus, deficient NMDAR functioning may contribute to abnormal selective attention in schizophrenia.

Acoustic Stimulation↗
PubMed2005

Deviance-related electrophysiological activity in mice: is there mismatch negativity in mice?

OBJECTIVE: Mismatch negativity (MMN) is an auditory event-related potential (ERP) that provides an index of auditory sensory memory and has become an important tool to investigate auditory sensory memory in cognitive neuroscience and disorders such as schizophrenia and dyslexia. The development of a mouse model of human MMN would permit to investigate the molecular biology of normal and dysfunctional MMN generation. However, the presence of MMN-like electrophysiological activity in mice has not been demonstrated. METHODS: Deviance-related ERPs were recorded in awake mice using 3 frequency deviance paradigms and one duration deviance paradigm. These paradigms were modelled after paradigms used in human studies to characterize MMN. RESULTS: Significant deviance-related activity was observed in all paradigms. However, in all frequency deviance paradigms this activity manifested as an enhancement of similar activity to the standard due to differences in stimulation rate between deviant and standard stimuli rather than qualitatively different MMN-like activity. In the duration deviance paradigm negative deflections were observed that showed characteristics typical of human MMN. CONCLUSIONS: MMN-like activity can be observed in mice in duration deviance paradigms. In frequency deviance paradigms effects of different stimulation rates of deviant and standard stimuli seem to be the main determinants of deviance-related activity. SIGNIFICANCE: Investigations of MMN-like ERPs in mice may permit to investigate the molecular basis for normal and abnormal MMN generation in neuropsychiatric disorders and dyslexia.

Acoustic Stimulation↗
PubMed2001

[Drug treatment of functional psychotic disorders].

Psychotic symptoms occur in different psychiatric disorders. The principles of antipsychotic drug treatment of various non-organic psychotic disorders are discussed. In particular, the role of the so-called atypical antipsychotics is highlighted.

Acute Disease↗
PubMed2001

Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.

BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.

Adult↗
PubMed2001

[Treatment of panic disorder with combination of SSRI and cognitive-behavioral therapy].

GOAL: Various forms of treatment of panic disorder with and without agoraphobia have shown good results. We examined the combination of cognitive-behavioral psychotherapy and treatment with an SSRI. METHODS: Case report and literature review. RESULT: The combination treatment shows a faster onset of therapeutic effects than cognitive-behavioral psychotherapy. However, final outcomes are comparable. CONCLUSIONS: The addition of a SSRI to cognitive-behavioral psychotherapy accelerates the onset of therapeutic effects. It does not interfere with the cognitive restructuring aimed at cognitive-behavioral psychotherapy.

Adult↗
PubMed2000

Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

BACKGROUND: In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. METHODS: In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. RESULTS: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. CONCLUSIONS: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

Adult↗
PubMed1998

Effects of clozapine on auditory event-related potentials in schizophrenia.

BACKGROUND: Schizophrenia is associated with cognitive deficits that are an intrinsic component of the disorder. Clozapine is an atypical antipsychotic that is superior to typical agents in the treatment of positive symptoms. The degree to which clozapine ameliorates cognitive deficits, however, is still controversial. Mismatch negativity (MMN), N200 (N2), and P300 (P3) are cognitive event-related potentials (ERPs) that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits associated with schizophrenia. In schizophrenic patients deficient generation of MMN, N2, and P3 has been observed, suggesting impairments of discrete stages of information processing. METHODS: This study investigates the effects of clozapine treatment on MMN, N2, and P3 generation. Patients were recruited from a haloperidol-controlled, double-blind treatment study of clozapine in chronic schizophrenia. ERPs were obtained at the beginning of the study and after 9 weeks (4 patients) and 16 weeks (13 patients) of treatment. RESULTS: Clozapine treatment was associated with a significant increase of P3 amplitude, which was not observed in the haloperidol group; however, clozapine treatment did not affect deficits in MMN and N2. CONCLUSIONS: These findings suggest that clozapine--in contrast to conventional antipsychotics--improves electrophysiological measures of attention-dependent information processing, but does not ameliorate preattentive deficits.

Adult↗
PubMed1998

The prevalence of acute extrapyramidal signs and symptoms in patients treated with clozapine, risperidone, and conventional antipsychotics.

BACKGROUND: Acute extrapyramidal side effects (EPS) are a common phenomenon of treatment with conventional antipsychotics. Previous studies found that clozapine has little propensity to cause EPS, while risperidone produces some EPS, but at levels lower than those of conventional antipsychotics. METHOD: We compared the prevalence and severity of EPS in patients treated with clozapine, risperidone, or conventional antipsychotics for at least 3 months. Our main hypothesis was that there would be differences between the three treatment groups with regard to akathisia, measured with the Barnes Akathisia Scale, and extrapyramidal motor side effects (rigidity, rigidity factor, tremor, salivation), measured with the Simpson-Angus scale. Secondarily, we were interested in possible differences between the three groups with respect to the anticholinergic comedication and the subjective impression of the patients, measured with the van Putten scale. RESULTS: We studied 106 patients (41 patients treated with clozapine, 23 patients with risperidone, and 42 patients treated with conventional antipsychotics). The sample was 57.5% male and had a mean +/- SD age of 36.6 +/- 9.3 years. The mean dose of antipsychotics calculated in chlorpromazine equivalents was 425.6 +/- 197.1 mg/day in the clozapine group, 4.7 +/- 2.1 mg/day in the risperidone group, and 476.5 +/- 476.9 mg/day in the group treated with conventional antipsychotics. The point-prevalence of akathisia was 7.3% in the clozapine group, 13% in the risperidone group, and 23.8% in the group treated with conventional antipsychotics. The point-prevalence of rigidity and cogwheeling respectively was 4.9% and 2.4% in the clozapine group, 17.4% and 17.4% in the risperidone group, and 35.7% and 26.2% in the group treated with conventional antipsychotics. CONCLUSION: Our results indicate that risperidone is superior to conventional neuroleptics in that it causes fewer EPS. In comparison to clozapine, risperidone produces EPS levels that are intermediate between clozapine and conventional antipsychotic drugs.

Acute Disease↗
PubMed1996

Gender differences in neuroleptic nonresponsive clozapine-treated schizophrenics.

Gender differences in neuroleptic-refractory chronic schizophrenic disorder patients were examined to determine whether a superior or equivalent antipsychotic response in women vs. men existed similar to that of the general schizophrenic population. Sixty-nine DSM-III schizophrenic patients (47 males and 22 females) were treated with clozapine using a standardized medication regime. The gender differences in these neuroleptic-nonresponsive chronic schizophrenic disorder patients differed from those previously observed in the general schizophrenic population in that an equivalent antipsychotic treatment response in females versus males was not found. These treatment-refractory women appear to be a severely ill subgroup of female schizophrenics with distinct onset of illness, course and treatment response characteristics.

Adolescent↗
PubMed1996

Medical complications of new antipsychotic drugs.

Although antipsychotic drugs have a high therapeutic index (ratio of clinical benefit to adverse effects), they are associated with a range of adverse effects in most patients. The majority of these side effects are tolerable, readily managed, and not life threatening. The most troublesome side effects are neurological. Two new antipsychotics (clozapine and risperidone) have recently been introduced and are the first of a new generation of compounds that may further improve the therapeutic index of routine antipsychotic drug administration. Clozapine clearly has a reduced risk of drug-induced parkinsonism, akathisia, and tardive dyskinesia, while producing an increased risk of agranulocytosis, seizures, and weight gain. Risperidone at low doses produces relatively few parkinsonian side effects, but it can cause tardive dyskinesia (though relative risk remains to be established). Risperidone has not been associated with blood dyscrasias or increased risk of seizures, but weight gain can be a problem for some patients. Neuroleptic malignant syndrome has been reported with both drugs, but relative risk has not been established.

Agranulocytosis↗
PubMed1995

Risperidone: efficacy and safety.

This article reviews the evidence for the efficacy and effectiveness of risperidone in persons with schizophrenia. Nine published double-blind studies compare risperidone with another antipsychotic medication and/or placebo. All were conducted in the acute phase of illness. Risperidone's antipsychotic efficacy is shown to be consistently superior to that of placebo and at least comparable to that of haloperidol and perphenazine for patients in the acute phase of schizophrenia. Further research is necessary to determine the effectiveness of risperidone and its efficacy both as a maintenance treatment and in treatment-refractory and deficit-state patients.

Acute Disease↗
PubMed1995

Postictal and chronic psychoses in patients with temporal lobe epilepsy.

OBJECTIVE: This study sought to elucidate the relation of clinical, neuropsychological, and seizure variables to chronic and postictal psychoses in patients with temporal lobe epilepsy. METHOD: Forty-four patients with treatment-refractory temporal lobe epilepsy were given formal psychiatric evaluations; 29 patients had no psychiatric disorder or a nonpsychotic disorder, eight patients had postictal psychoses, and seven patients had chronic psychoses. Comparisons of clinical, neuropsychological, magnetic resonance imaging, and seizure variables were made between the nonpsychotic and the psychotic patients and, secondarily, between the patients with transient postictal psychoses and those with chronic psychoses. RESULTS: Bitemporal seizure foci, clustering of seizures, and absence of febrile convulsions were associated with both postictal psychoses and chronic psychoses. Younger age at onset of epilepsy and lower verbal and full-scale IQs differentiated the patients with chronic psychoses from those with postictal psychoses. CONCLUSIONS: Patients with temporal lobe epilepsy with chronic and postictal psychoses show similar profiles of clinical and seizure variables, suggesting shared etiologic factors. These factors may increase the propensity to develop psychotic symptoms, while other factors, such as time of onset of epilepsy and underlying neuropathology, may determine whether transient or chronic psychotic symptoms develop. Even among patients with treatment-refractory temporal lobe epilepsy, a specific subgroup of patients, characterized by bitemporal seizure foci, an absence of febrile convulsions, and a history of clustering of seizures, appears to be particularly prone to develop psychotic disorders. A process similar to secondary epileptogenesis may be involved in the development of the psychoses.

Adult↗
PubMed1987

[Essential cryoglobulinemia with glomerulonephritis as a variant of the purpura-arthralgia-nephritis syndrome].

The syndrome of mixed cryoglobulinemia is clinically characterized by the findings of purpura, arthralgia and glomerulonephritis, the latter developing in up to 50% of the cases. The cryoglobulins have rheumatoid factor activity and serum levels of complement factor C4 are significantly reduced. A report is presented on seven patients with a typical purpura-arthralgia-nephritis syndrome and two patients with essential cryoglobulinemia, rheumatoid factor activity and glomerulonephritis without extrarenal manifestations of vasculitis. Based on these observations, measurement of rheumatoid factor activity is recommended in serum of patients with unclassified glomerulonephritis.

Complement C3↗