Biomedical subjects

D Hell

Publications and source records attributed to D Hell.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2000

[Fundamentals of scientifically based ethics in the works of Eugen Bleuler].

The name Eugen Bleuler is almost exclusively linked with matters concerning the nosology of schizophrenia, general psychopathology, and the relationship of clinical psychiatry with psychoanalysis. His bibliography lists various works dealing with contemporary themes about legislation, the fight against alcoholism, and, for the most part from later years, with themes about general psychology. In this article, material from Bleuler's texts are reviewed, including some which have been inaccessible up to now, which either allow interpretative conclusions on ethical grounds or have this explicitly as a topic. In particular, the analysis focuses on Bleuler's work "The Scientific Fundamentals of Ethics", published in 1939. Written in a time widely viewed as disorientated, the author coherently and systemically comments on the issue of a 'new' ethic. The anti-religious and anti-philosophical positions already demonstrable in some of his earlier works will be shown. According to his conception of a scientifically based ethic, the idea of social suitability is of utmost importance and also recognisable in the animal world as a general principle of nature. Bleuler perceives the ethical 'instinct' as inherent; its absence characterises the image of an 'moral idiot', which was already a theme in his earlier works. His statements about matters concerning euthanasia are presented and, furthermore, it will be attempted to construct from his texts an underlying global view. Concerning these ethical issues, it also can be shown once more that the elderly Bleuler was hardly influenced by psychoanalytical perspectives.

Ethics, Medical↗

PubMed2000

Personality and object relations in patients with affective disorders: idiographic research by means of the repertory grid technique.

BACKGROUND: This paper presents an idiographic approach to evaluate the self concept and the self-object-relationship of patients suffering from affective disorders. METHODS: Significant dimensions of the personality and the object relations of 127 depressive patients and 34 orthopaedic patients were investigated with the repertory grid-technique. The self concept and the object relations were compared by means of nomothetically used idiographic results after recovery from manifest depression. RESULTS: 'Low self esteem' was frequently found in patients with a long lasting course of illness and the ICD-10-diagnoses of 'bipolar affective disorder' and 'dysthymia'. The object relations of the depressive sample were characterised by the dimension 'symbiotic near'; 'ambivalent' and 'indifferent' partnership relationships were found much more frequently in the controls. CONCLUSIONS: The idiographic results help to differentiate the spectrum of affective disorders. They underline the importance of the interpersonal dimension of depression and may be used as a basis of a therapeutic appraisal. LIMITATIONS: The repertory grid-technique may not be used as a diagnostic instrument. However, the combination of idiographic results with further clinical informations enables the multidimensional assessment of the self concept and psychosocial coping mechanisms.

Adaptation, Psychological↗

PubMed2000

Psychological and physiological effects of MDMA ("Ecstasy") after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans.

MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") mainly releases serotonin and dopamine. In animals, pretreatment with 5-HT(2) antagonists has been shown to attenuate neurochemical and behavioral effects of MDMA. In humans, the role of 5-HT(2) receptors in the action of MDMA has not been studied. We investigated the effect of pretreatment with the 5-HT(2A/C) antagonist ketanserin (50 mg p.o.) on subjective responses to MDMA (1.5 mg/kg p.o.) in 14 healthy volunteers using a double-blind placebo-controlled within-subject design. Subjective effects were rated by psychometric rating scales. Physiological effects measured were blood pressure, heart rate, and body temperature. Adverse effects were assessed during the sessions, and after one and three days. Ketanserin attenuated MDMA-induced perceptual changes, emotional excitation, and acute adverse responses but had little effect on MDMA-induced positive mood, well-being, extroversion, and short-term sequelae. Body temperature was lower under MDMA plus ketanserin compared to MDMA alone. The results suggest a contributing role for 5-HT(2) receptors in the action of MDMA in humans.

Adult↗

PubMed2000

3,4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H(2)(15)O]-PET in healthy humans.

[H(2)(15)O]-Positron Emission Tomography (PET) was used to examine regional cerebral blood flow (rCBF) after administration of a single oral dose of the serotonin realeaser and uptake inhibitor MDMA (1.7 mg/kg) or placebo to 16 MDMA-naïve subjects. Psychological changes were assessed by psychometric rating scales. MDMA produced distributed changes in regional blood flow including increases in ventromedial frontal and occipital cortex, inferior temporal lobe and cerebellum; and decreases in the motor and somatosensory cortex, temporal lobe including left amygdala, cingulate cortex, insula and thalamus. Concomitant with these changes, subjects experienced heightened mood, increased extroversion, slight derealization and mild perceptual alterations. MDMA also produced increases in blood pressure and several side effects such as jaw clenching, lack of appetite and difficulty concentrating. These results indicate that a distributed cluster of brain areas underlie the various effects of MDMA in humans.

Adult↗

PubMed2000

Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.

Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.

Adolescent↗

PubMed2000

[Who is rehospitalized in a psychiatric hospital? Psychiatric hospitalization rates and social indicators in the Zurich canton (Switzerland)].

There are two approaches in the research on the relation between social conditions and mental disorder: The ecological approach is concerned with characteristics of the social composition of a certain geographical area and their relation to the frequency of disorders, whereas for the individualistic view variables of the psychosocial background of the individual are of interest. This study is on the risk for psychiatric admission (first and re-admission). While considering variables of the social context of the community as well as of the background of the individual, it tries to take into account both the ecological and the individualistic view of the relationship between social conditions and (treated) mental disorder. The sample of the study includes data of 4021 psychiatric inpatients treated in 1997 in one of the seven psychiatric hospitals of the Swiss canton of Zurich as well as data of social context of the 171 communities of the canton of Zurich. The psychiatric first and re-admission rates of the community can be predicted by the following variables of its social context: 1. pro portion of foreigners, 2. urban character of the living area, 3. population density. Two other variables are of relevance only for the prediction of first admissions: 4. proportion of one-person households and 5. local tax rate. However, further results of the study show that correlations between variables of the social context and psychiatric admission rate of the community cannot be interpreted as risks for the individual.

Adult↗

PubMed2000

[Psychic pain as a symptom of depression. Phenomenology and neurobiology].

In a review of the relevant literature the experience of pain in depression is emphasized. There is evidence for a central pain disturbance mediating the 'psychic pain' experience in severe major depressive episodes with a predominance of anxiousness and agitation. This phenomenological concept has not been considered as a specific construct in modern descriptive classification systems such as DSM-IV or ICD-10. The purpose of this article is to provide an overview of recent partially independent developments in depression and experimental pain research with emphasis on the neuroanatomy of the rostral limbic system and the medial pain system. The available evidence is consistent with the hypothesis that overlapping anatomic structures of the medial pain system are activated during the experience of both the psychic pain of depression and the motivational-affective component of acute, tonic pain. This specific hypothesis can be tested with modern functional neuroimaging.

Depressive Disorder↗

PubMed2000

Effectiveness of inpatient drug detoxification: links between process and outcome variables.

The Psychiatric University Hospital of Zürich offers a 2-week residential detoxification treatment program for patients abusing illegal drugs. 96 out of 160 patients were interviewed at three intervals: upon admission, on the 10th day of treatment, and about 1 month after leaving the clinic. Approximately 17% of the patients were completely abstinent 1 month after treatment. About 50% of the patients could give up the consumption of particular drugs. For around one third of the dependents, the drug consumption remained the same or had increased. The analysis of the predictors of drug consumption after treatment stresses the importance of the social integration of the dependents before detoxification as well as of characteristics of the treatment process (relapse, dropping out of treatment, and referral to a follow-up program).

Adult↗

PubMed2000

[Reconstruction of mutism. Studies of subjective experiences of former patients with the modified Landfield categories].

OBJECTIVE: The subjective experience of catatonic patients was investigated with the repertory grid-technique after recovery from the acute state of disease and compared with non-catatonic schizoaffective and depressive patients. METHODS: The sample consists of 18 catatonic patients, 22 schizoaffective, 16 unipolar depressive, 8 unipolar manic and 23 patients with bipolar affective disorder as well as of 32 psychiatrically healthy orthopaedic controls. Interviews were held well before discharge. The contents of personal constructs was analyzed by means of modified Landfield categories. RESULTS: "Self" of catatonic patients did not differ significantly from the other groups. The "Idealself" of catatonic patients differed significantly in the categories "high self esteem" (from the controls and the non-catatonic group) and "high empathy" (from the controls). The "disease-self" ("In the acute catatonic state") was construed as isolated (lack of social contact). The results underline the importance of an active therapeutical interaction in the acute catatonic state. The modified Landfield Categories proved to be a useful psychodiagnostic instrument for the idiographic assessment of personality in particular, and for psychiatric therapy research in general.

Adult↗

PubMed1999

Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study.

BACKGROUND: Our goal was to examine spatial working memory function in relation to clinical symptoms of schizophrenia over a period of 4 months. METHODS: We assessed spatial working memory, spatial detection and clinical symptoms in 34 acutely psychotic schizophrenia patients within the first 2 weeks of hospitalization, and 4 months later. Spatial working memory was assessed by a delayed response task. A spatial control task was included to rule out simple sensorimotor deficits. Positive and negative symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Thirty-nine matched normal control subjects were also examined on the same tasks over the same period. RESULTS: Patients showed deficits in working memory, but they performed well on the spatial control task. Both positive and negative symptoms improved at the 4-month follow up. Spatial working memory also improved over time but there was still a significant deficit at the follow-up session. CONCLUSIONS: These results indicate that both symptoms and spatial working memory improved 4 months after the initial hospitalization but spatial working memory, hypothesized to be mediated by the dorsolateral prefrontal system, did not normalize. Thus, spatial working memory deficit may be a stable marker for schizophrenia.

Acute Disease↗

PubMed1999

Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic-naive, first-episode, productive schizophrenia.

Functional imaging of brain electrical activity was performed in nine acute, neuroleptic-naive, first-episode, productive patients with schizophrenia and 36 control subjects. Low-resolution electromagnetic tomography (LORETA, three-dimensional images of cortical current density) was computed from 19-channel electroencephalographic (EEG) activity obtained under resting conditions, separately for the different EEG frequencies. Three patterns of activity were evident in the patients: (1) an anterior, near-bilateral excess of delta frequency activity; (2) an anterior-inferior deficit of theta frequency activity coupled with an anterior-inferior left-sided deficit of alpha-1 and alpha-2 frequency activity; and (3) a posterior-superior right-sided excess of beta-1, beta-2 and beta-3 frequency activity. Patients showed deviations from normal brain activity as evidenced by LORETA along an anterior-left-to-posterior-right spatial axis. The high temporal resolution of EEG makes it possible to specify the deviations not only as excess or deficit, but also as inhibitory, normal and excitatory. The patients showed a dis-coordinated brain functional state consisting of inhibited prefrontal/frontal areas and simultaneously overexcited right parietal areas, while left anterior, left temporal and left central areas lacked normal routine activity. Since all information processing is brain-state dependent, this dis-coordinated state must result in inadequate treatment of (externally or internally generated) information.

Acute Disease↗

PubMed1999

[Muscle strength and gait patterns of depressed people].

BACKGROUND: Gait characteristic and muscle power are often described in the clinical literature but with little empirical support. We assessed some parameters of gait and muscle power using simple and standardized methods within a framework based principally on classic clinical observations of depression. METHOD: 20 depressed inpatients were examined with standard tests of isometric muscle power and gait parameters, which measure step length, average walking speed, maximal walking speed, and three-minute walk distance. The results were compared with those of 20 matched healthy controls. The examination procedure was repeated after a three week period of inpatient treatment and significant symptomatic improvement. RESULTS: As predicted by our hypothesis depressed patients' muscle power and gait characteristics differed clearly from normal controls. Significant improvements after 3 weeks of inpatient treatment were found above all in extension of the knee and extension of the elbow tests as well as in all measures of our gait analysis. However, all gait parameters still differed significantly from those of healthy controls. CONCLUSIONS: Using simple but reliable tests which were used for the first time in psychiatry we examined certain relationships between depression and motor function in a moderately to severely depressed inpatient sample.

Case-Control Studies↗

PubMed1999

Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans.

RATIONALE: Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers. OBJECTIVE: In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies. METHODS: Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA. RESULTS: As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects. CONCLUSIONS: This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.

Acoustic Stimulation↗

PubMed1999

A deviant EEG brain microstate in acute, neuroleptic-naive schizophrenics at rest.

Momentary brain electric field configurations are manifestations of momentary global functional states of the brain. Field configurations tend to persist over some time in the sub-second range ("microstates") and concentrate within few classes of configurations. Accordingly, brain field data can be reduced efficiently into sequences of re-occurring classes of brain microstates, not overlapping in time. Different configurations must have been caused by different active neural ensembles, and thus different microstates assumably implement different functions. The question arises whether the aberrant schizophrenic mentation is associated with specific changes in the repertory of microstates. Continuous sequences of brain electric field maps (multichannel EEG resting data) from 9 neuroleptic-naive, first-episode, acute schizophrenics and from 18 matched controls were analyzed. The map series were assigned to four individual microstate classes; these were tested for differences between groups. One microstate class displayed significantly different field configurations and shorter durations in patients than controls; degree of shortening correlated with severity of paranoid symptomatology. The three other microstate classes showed no group differences related to psychopathology. Schizophrenic thinking apparently is not a continuous bias in brain functions, but consists of intermittent occurrences of inappropriate brain microstates that open access to inadequate processing strategies and context information

Adult↗

PubMed1999

5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man--a PET study with [11C]raclopride.

The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states.

Adult↗

PubMed1999

EEG differences in monozygotic twins discordant and concordant for schizophrenia.

In an electroencephalographic (EEG) study of 27 pairs of monozygotic (MZ) twins discordant for schizophrenia, 13 pairs of MZ twins concordant for schizophrenia, 40 pairs of healthy MZ twins, and 91 healthy, unrelated subjects with repeated assessments, we investigated (a) the trait quality of brainwave patterns with respect to interindividual differences, intraindividual stability over time, and within-pair MZ concordance; (b) the EEG characteristics that enable discrimination between affected and unaffected individuals; and (c) the EEG characteristics that reflect the severity of illness. In comparison with healthy control subjects, the MZ twins who were discordant and concordant for schizophrenia exhibited a much lower within-pair EEG concordance, so that EEG abnormalities associated with schizophrenia and manifested differently in the co-twins concordant for schizophrenia seemed to reflect nongenetic, pathological developments of genetically identical brains.

Adolescent↗

PubMed1999

[The general psychological concept in the later work of Eugen Bleulers. Comparison with a summarized description from a forgotten theory 60 years after the final publication (1939)].

Documents by Eugen Bleuler from 1921 to 1939 that go into general psychological topics of meaning of consciousness, formation of motive and will, are presented. An effort towards integration of seemingly incompatible, side by side standing, unrelated biological and psychological concepts that probably is most likely explainable by the contemporary background of ideas, is recognizable. In this context, Eugen Bleuler refers to an already (especially by Richard Semon) systematically developed theory called "Mnemism" that he interpreted and applied to the psychological circumstances mentioned above. That theory of "mnemism" that can be most adequately described as a biogenetic-vitalistic theory, is assuming, that all organic life--independent of the possibility of a self-reflecting consciousness--is able to learn experiences made by analysis of environment and to pass it on following generations. Pattern of stimulus reactions are in the sense of this theory memorized ("engraphiert") and reactivated under similar situational circumstances ("ekphoriert") by the psychological mode of association.--It can be shown that Bleuler pursued this theory for a period of more than ten years. It represents the benchmark for Bleuler's standpoints, for example for the question of determination of human acting, that as itselves are already known from his earlier documents, but here have found a more theoretically based explanation. The assumption of the efficacy of specific, not necessary consciously remembered "engramms" of memory, suggests the hypothesis of the existence of unconsciousness; in this context textual points of contact to the psychological concepts of S. Freud and C. G. Jung--mnemic memory and collective unconscious--are shown.

Consciousness↗