Biomedical subjects

Daniel Hell

Publications and source records attributed to Daniel Hell.

17 recordsLinked to original sources

PubMed2006

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study.

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia.

Adult↗

PubMed2006

Effects of psilocybin on time perception and temporal control of behaviour in humans.

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Adult↗

PubMed2006

Affective judgment and beneficial decision making: ventromedial prefrontal activity correlates with performance in the Iowa Gambling Task.

Damasio proposes in his somatic marker theory that not only cognitive but also affective components are critical for decision making. Since affective judgment requires an interplay between affective and cognitive components, it might be considered a key process in decision making that has been linked to neural activity in ventromedial prefrontal cortex (VMPFC). Using functional magnetic resonance imaging (fMRI), we examined the relationship between VMPFC, emotionally (unexpected)- and cognitively (expected)-accentuated affective judgment, and beneficial decision making (Iowa Gambling Task; IGT) in healthy subjects. Neuronal activity in the VMPFC during unexpected affective judgment significantly correlated with both global and final performance in the IGT task. These findings suggest that the degree to which subjects recruit the VMPFC during affective judgment is related to beneficial performance in decision making in gambling.

Adult↗

PubMed2005

Voluntary vs. involuntary hospital admission in acute mania of bipolar disorder: results from the Swiss sample of the EMBLEM study.

BACKGROUND: Patients with acute mania in bipolar disorder require pharmacological treatment to reduce symptoms. In addition, it is recognised that admission status is a clinically relevant aspect of bipolar disorder. There is, however, a lack of published data assessing the association of admission status with clinical or functional outcomes. The European-Mania-in-Bipolar-Longitudinal-Evaluation-of-Medication (EMBLEM) study has been designed to describe outcomes associated with medication therapies. Baseline data from this study are now available and we used these data to examine the characteristics of patients with acute mania in the Swiss EMBLEM cohort who were admitted involuntary and voluntary, respectively, and their functional and clinical status. METHODS: Ninety-five patients with an acutely manic or mixed episode of bipolar disorder were included in the Swiss cohort of the study. Patients' history, psychosocial functioning, clinical measures of mania and depression, pharmacological and compliance variables were assessed. Statistical methods comprised univariate analyses of variance and logistic regression analyses to elucidate associations between variables of interest. RESULTS: Patients with involuntary hospital admission (n = 55) were more aggressive and had less insight. They had a more frequent history of substance abuse and were less likely to take anticonvulsants or lithium. Furthermore, these patients showed lower compliance, which also guided physicians' decision on pharmacotherapy. LIMITATION: The EMBLEM study had an observational and non-interventional design; therefore it was not possible to compare treatment groups by means of stringent between-group analyses. However, a main target of this study was to gather clinically relevant information on outcomes of acute mania associated with currently available medication therapies. CONCLUSIONS: Involuntary admission status was significantly associated with clinical status, especially aggression and also compliance. Admission status in bipolar patients plays a clinically important role.

Acute Disease↗

PubMed2005

Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study.

Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.

Adult↗

PubMed2005

NMDA hypofunction in the posterior cingulate as a model for schizophrenia: an exploratory ketamine administration study in fMRI.

BACKGROUND: Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. METHODS: We investigated 16 healthy subjects which were assigned to either placebo (n = 7; saline) or ketamine (n = 9; 0.6 mg/kg/h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. RESULTS: The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. CONCLUSION: The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia.

Adult↗

PubMed2005

Lateralization of cerebral hemodynamics during Wisconsin Card Sorting Test: a functional transcranial Doppler sonography study.

OBJECTIVE: Studies on lateralization of cerebral metabolism during Wisconsin Card Sorting Test (WCST), a well-known paradigm of category learning, have shown mixed results. Moreover, sorting dimension (number, color and shape) is a cofounder of laterality in WCST. Functional transcranial Doppler sonography (fTCD) has a high temporal resolution and allows the measurement of mean cerebral blood flow velocity (CBFV) in the middle (MCA) and anterior cerebral arteries (ACA), which supply lateral and medial parts of the frontal and parietal lobes, respectively. We used fTCD to investigate CBFV changes occurring in both MCA and ACA during WCST and different sorting dimensions. METHODS: Twenty-one subjects underwent twice two distinct phases of the WCST, namely maintaining a rule (maintaining set) and searching for a new rule (set shifting), during bilateral fTCD of the MCA and ACA. RESULTS: There was a left-sided dominance of CBFV during maintaining set and set shifting in the MCA. CBFV was not associated with test performance. The sorting dimension number caused the highest CBFV increase in both MCA and ACA during maintaining set, and the sorting dimension shape caused lowest CBFV decrease in both MCA during set shifting. CONCLUSIONS: This study confirms results that cerebral blood flow (CBF) lateralizes to the left side during WCST. The 3 sorting dimensions provoked distinct processing speed during maintaining set and set shifting, but caused no effect on hemispheric lateralization. SIGNIFICANCE: Functional transcranial Doppler sonography can be used to assess CBFV during WCST and different sorting dimensions, and the latter modulate reaction time and cerebral hemodynamics.

Adult↗

PubMed2005

Modulating the rate and rhythmicity of perceptual rivalry alternations with the mixed 5-HT2A and 5-HT1A agonist psilocybin.

Binocular rivalry occurs when different images are presented simultaneously to corresponding points within the left and right eyes. Under these conditions, the observer's perception will alternate between the two perceptual alternatives. Motivated by the reported link between the rate of perceptual alternations, symptoms of psychosis and an incidental observation that the rhythmicity of perceptual alternations during binocular rivalry was greatly increased 10 h after the consumption of LSD, this study aimed to investigate the pharmacology underlying binocular rivalry and to explore the connection between the timing of perceptual switching and psychosis. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, PY) was chosen for the study because, like LSD, it is known to act as an agonist at serotonin (5-HT)1A and 5-HT2A receptors and to produce an altered state sometimes marked by psychosis-like symptoms. A total of 12 healthy human volunteers were tested under placebo, low-dose (115 microg/kg) and high-dose (250 microg/kg) PY conditions. In line with predictions, under both low- and high-dose conditions, the results show that at 90 min postadministration (the peak of drug action), rate and rhythmicity of perceptual alternations were significantly reduced from placebo levels. Following the 90 min testing period, the perceptual switch rate successively increased, with some individuals showing increases well beyond pretest levels at the final testing, 360 min postadministration. However, as some subjects had still not returned to pretest levels by this time, the mean phase duration at 360 min was not found to differ significantly from placebo. Reflecting the drug-induced changes in rivalry phase durations, subjects showed clear changes in psychological state as indexed by the 5D-ASC (altered states of consciousness) rating scales. This study suggests the involvement of serotonergic pathways in binocular rivalry and supports the previously proposed role of a brainstem oscillator in perceptual rivalry alternations and symptoms of psychosis.

Adult↗

PubMed2004

Cerebral hemodynamics and processing speed during category learning.

The Wisconsin Card Sorting Test (WCST) is a commonly used paradigm of category learning with two alternating and distinct processes, maintaining set and set shifting that have been characterized by functional transcranial Doppler sonography (fTCD) of the basal cerebral arteries. Further, repeated WCST administrations resulted in improved speed of solution. This study addressed the question of whether optimised speed during maintaining set or set shifting is associated with changes of cerebral hemodynamics as measured by bilateral fTCD. During maintaining set, improved speed was associated with increased peak mean cerebral blood flow velocity (CBFV) of the anterior cerebral arteries. These results suggest a common functional substrate between optimised speed of solution and cerebral hemodynamics during maintaining set.

Adult↗

PubMed2004

Early treatment-induced improvement of negative symptoms predicts cognitive functioning in treatment-naive first episode schizophrenia: a 2-year followup.

Studying neuroleptic-naive first episode schizophrenia is a strategy for investigating clinical and neuropsychological abnormalities at a very early phase of the disease without confounding influences of illness duration and medication effects. We examined the clinical and neuropsychological time course over 2 years in 32 neuroleptic-naive first episode patients (20 males, 12 females) and 21 healthy individuals with similar sociodemographic characteristics. Early treatment-induced reduction of negative symptoms predicted superior cognitive performance throughout followup in the domains of verbal fluency, attention, and non-verbal learning and memory. There were no associations between psychotic or disorganized symptoms and cognitive variables. These findings suggest an important relationship between treatment efficacy of antipsychotic medication and the longer term course of cognitive deficits in schizophrenia.

Adolescent↗

PubMed2003

Visual object working memory function and clinical symptoms in schizophrenia.

OBJECTIVE: The presence of working memory deficits suggests abnormalities of prefrontal cortex (PFC) in schizophrenia. Although much is known about spatial working memory deficits in schizophrenia, including its potential as a phenotypic marker, it is unclear whether object working memory is similarly affected. Our goal was to examine nonspatial, object working memory function in relation to clinical symptoms. METHODS: We assessed object working memory and clinical symptoms in 28 schizophrenia patients during acute psychotic episode and 4 months later during partial remission. Delayed-matching-to-sample tasks for familiar object (DMTS-F) and novel shapes (DMTS-N) were used. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). 33 age-matched normal subjects were also tested over the same time period. RESULTS: Acutely psychotic patients showed deficits in both DMTS-F and DMTS-N. Four months later, their DMTS-F performance improved significantly but deficits in DMTS-N were still present. During acute psychosis, symptoms correlated with DMTS-F but not with the DMTS-N. Four months later, negative symptoms correlated with both tasks. CONCLUSIONS: Object working memory as measured by DMTS-N was impaired in schizophrenia patients during both acute and chronic states. When schizophrenia patients were in partial remission, object working memory was associated with negative symptoms.

Acute Disease↗

PubMed2003

[Self-esteem and partner relationships of patients with bipolar affective disorder: a study of the interval personality with the Giessen-test].

The self-concept and the partner relationships of patients with bipolar affective disorder in remission were investigated with the Giessen-Test (GT, Beckmann et al. ) comparing the bipolar patients with unipolar depressive patients, a control group of orthopedic patients and the standard sample of the Giessen-Test. The new dimensions "self-esteem" and "near-to-object" were developed by means of the Giessen-Test items. Self-esteem was significantly lower in bipolar patients in remission than in the controls. The bipolar patients also described themselves as "more distant to others" than the controls. Bipolar and unipolar-depressive patients had a similar self-concept and view of their partner relationships. The results underline the importance of the regulation of self-esteem and the interpersonal dimension in the long-term course of bipolar affective disorder. Therapeutic implications are discussed.

Adult↗

PubMed2003

Long-term course of schizophrenic illness: Bleuler's study reconsidered.

OBJECTIVE: The influential 1972 study by Manfred Bleuler on the long-term course of schizophrenic illness has been reconsidered. The authors tested the diagnosis of schizophrenia in all patients and investigated how the distribution of the types of illness course and outcome would change after exclusion of patients whose diagnosis of schizophrenia could not be confirmed by modern diagnostic standards. METHOD: Clinical charts and Bleuler's research notes on the original sample were assessed, and all patients were rediagnosed with the help of DSM-IV, DSM-III-R, ICD-10, the Research Diagnostic Criteria (RDC), Schneider's criteria, and an operationalized version of the criteria of Eugen Bleuler. RESULTS: The diagnosis of schizophrenia was not confirmed in about 30% of the sample; the majority of these patients were rediagnosed with schizoaffective disorder. High diagnostic agreement was found between DSM-IV, DSM-III-R, ICD-10, and RDC; there was much less agreement with Bleuler's and Schneider's criteria. After exclusion of patients whose schizophrenia diagnosis was not confirmed, the proportion of patients with undulating course and recovery slightly decreased, and the proportion of patients with severe end state slightly increased. Nevertheless, the distribution of the types of long-term course did not significantly change, and even among patients with strictly defined schizophrenia, half had an undulating course with remissions and 12%-15% recovered. CONCLUSIONS: Schizophrenic illness remains heterogeneous with regard to illness course and outcome even when narrowly diagnosed with the help of modern operationalized diagnostic criteria. Contemporary differentiation between schizophrenic and schizoaffective disorders is prognostically valid.

Adolescent↗

PubMed2002

Temporal modulation of cerebral hemodynamics under prefrontal challenge in schizophrenia: a transcranial Doppler sonography study.

Transcranial Doppler sonography (TCD) is a non-invasive method to assess cerebral blood flow velocity (CBFV) and hence cerebral blood flow during cognitive activation. Major cognitive dysfunctions have been consistently reported in patients with schizophrenia, and important deficits have been observed with respect to prefrontal functions. However, prefrontal activation in schizophrenics has not been investigated with TCD despite its potential to examine short-term changes of cerebral blood flow. The Wisconsin Card Sorting Test (WCST) and the Tower of Hanoi puzzle were administered to 11 right-handed schizophrenics and 20 healthy controls. The middle and anterior cerebral arteries were pairwise insonated. Schizophrenics showed decreased CBFV during the initial phase of both prefrontal functions and the steady-state phase of the Tower of Hanoi. In healthy controls, there was a succession of three significantly different phases of mean CBFV during the Tower of Hanoi, and there was no such modulation in schizophrenics. Immediately after category shift in the WCST, there was an increase of mean CBFV in healthy controls, but not in schizophrenics. In conclusion, transcranial Doppler sonography was able to detect differing specific alterations of CBFV during two prefrontal tasks in healthy controls and patients with schizophrenia. Importantly, the results of this study imply a degraded pattern of CBFV changes over time in schizophrenia during prefrontal activation.

Adult↗

PubMed2002

Spatial selective attention and inhibition in schizophrenia patients during acute psychosis and at 4-month follow-up.

BACKGROUND: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state. METHODS: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed. RESULTS: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up. CONCLUSIONS: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.

Acute Disease↗

PubMed2002

[Employment situation of psychiatric in-patients with schizophrenic or affective disorders].

OBJECTIVE: This study is on employment on the competitive as well as the sheltered work market of psychiatric in-patients suffering from schizophrenia or affective disorders. Furthermore it investigates the importance of characteristics of disorder and of educational and vocational background as predictors of occupation. METHODS: A sample of 251 in-patients participated in a structured interview during their hospitalization. RESULTS: 43 % of in-patients suffering from schizophrenia and 46 % suffering from affective disorders were employed on the competitive work market during the year before index-hospitalization. Many were without any occupation too because sheltered employment was rarely used and mostly by schizophrenics (17 % vs 4 % of persons with affective disorders). Predictors of employment are past vocational experiences, education, length of past hospitalization, psychiatric diagnosis and sex. CONCLUSIONS: Results raise the question of deficits in providing with sheltered employment opportunities for the mentally ill and in particular for people suffering from affective disorders. Alternatives to these deficits are discussed.

Adult↗

PubMedDate not supplied

Eugen Bleuler and forensic psychiatry.

The list of Eugen Bleuler's writings shows that he grappled with forensic issues quite early, even before he became a full professor in 1898. Bleuler regularly prepared forensic criminal expert's reports himself until emeritus status was conferred on him in 1927. Analysis of his writings indicates that his position remained explicitly deterministic. In Bleuler's later work, that position was integrated into the natural philosophy vitalistic theory of mnemism, itself part of a more comprehensive theory, without any corrections to its content. Eugen Bleuler always remained a critic of criminal law, although it can be seen from later expert's reports that he for the most part accepted the existing system for the administration of justice for practical reasons. However, Bleuler always defended the idea that punishment should not be based on the moral guilt of the perpetrator but rather on the prospect of curing him.

Criminal Psychology↗