Biomedical subjects

Stephan Ruhrmann

Publications and source records attributed to Stephan Ruhrmann.

16 recordsLinked to original sources

PubMed2006

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Adolescent↗

PubMed2006

No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of psychiatric patients and control subjects.

BACKGROUND: It was recently reported that a rare functional variant, R441H, in the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk factor for unipolar major depression (UP) since it was originally found in 10% of UP patients (vs. 1.4% in control subjects). METHODS: We explored the occurrence of this variation in patients with affective disorders (n = 646), autism spectrum disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic panel of control individuals from North Africa, Sub-Saharan Africa, India, China, and Sweden (n = 277). RESULTS: Surprisingly, we did not observe the R441H variant in any of the individuals screened (3188 independent chromosomes). CONCLUSIONS: Our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to UP. The absence of the variant from a large cohort of psychiatric patients and control subjects suggests that the findings reported in the original study could be due to a genotyping error or to stratification of the initial population reported. Additional data by other groups should contribute to the clarification of the discrepancy between our results and those previous published.

Adult↗

PubMed2006

Neurocognitive functioning in subjects at risk for a first episode of psychosis compared with first- and multiple-episode schizophrenia.

Evidence from neurobiological studies suggests that schizophrenia arises from an early abnormality in brain development and possibly further progressive developmental mechanisms. Despite a delay between the acquisition of neuropathology and the triggering of psychosis, neurobiological susceptibility is likely to be expressed subclinically by biobehavioral markers in the premorbid stage. The exploratory study aims at identifying potential neurocognitive risk factors and investigating the unfolding of the illness within a cross-sectional design by comparing neurocognitive profiles in 179 healthy controls, 38 clinically identified subjects in an early initial prodromal state (EIPS) for psychosis, 90 subjects in a late initial prodromal state (LIPS), 86 first-episode patients with schizophrenia, and 88 multiple-episode patients. Subjects at risk were substantially impaired in verbal executive and verbal memory functions. Compared to EIPS subjects, LIPS subjects demonstrated additional attentional deficits. Both EIPS and LIPS subjects were superior to first-episode patients who presented a generalized neuropsychological deficit profile, and to multiple-episode patients who showed evidence for further decline. Although results were influenced by general intellectual abilities and demographic and clinical characteristics, they could not account for total group differences. Results support a neurodevelopmental model of psychosis with further progressive mechanisms and are consistent with a primary involvement of left frontotemporal networks in the prodromal phase.

Adult↗

PubMed2006

Alexithymia in obsessive-compulsive disorder - results from a family study.

BACKGROUND: Previous studies have suggested an association between alexithymia and obsessive-compulsive disorder (OCD). However, it is unclear to which extent alexithymic traits in OCD patients reflect familial deficits in cognitively processing and communicating feelings that are also present in their first-degree relatives. This study investigates the hypotheses of an elevated level of alexithymia in subjects with OCD and their first-degree relatives compared to controls and their first-degree relatives. METHODS: 82 cases with OCD and 169 first-degree relatives were compared to 76 controls and 144 first-degree relatives from a German family study on OCD (GENOS). All subjects completed the 20-item Toronto Alexithymia Scale (TAS-20). Direct or family informant interviews were carried out with the German version of the Schedule for Affective Disorders and Schizophrenia - lifetime version for anxiety disorders (DSM-IV). RESULTS: OCD was associated with significantly higher scores of alexithymia. However, first-degree relatives of OCD cases and of controls did not differ in TAS-20 scores. In linear regression analyses, the TAS-20 total score showed significant intrafamilial associations within the families of control subjects but not within families of OCD cases. CONCLUSION: OCD is a severe mental disorder that is associated independently from other current comorbid axis I disorders with deficits in identifying and expressing feelings. However, alexithymia does not represent a familial risk factor for OCD.

Adult↗

PubMed2006

Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects.

OBJECTIVE: Studies of the familiality of obsessive-compulsive disorder (OCD) have yielded inconsistent results. This study compared the familial aggregation of OCD in first-degree relatives of community subjects with never-treated OCD, outpatients with OCD, and comparison subjects. METHOD: Fifteen persons from the community with untreated OCD were matched on age and interview type (direct or through family informants) with 90 OCD patients from four treatment facilities and 70 comparison subjects. Direct or indirect interviews using the German-language version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Version for Anxiety Disorders (DSM-IV) were obtained from 58, 285, and 247 first-degree relatives, respectively, of the three groups. The rate of OCD in case versus comparison relatives was assessed with chi-square tests, and odds ratios were calculated for risk estimation. Cox proportional hazards analysis was used to estimate the age-related risk of relatives of being affected by OCD. RESULTS: Cox proportional hazards analyses revealed a 6.2-fold higher risk (hazard ratio) for relatives of all OCD cases for definite OCD and a 2.2-fold higher risk for subclinical OCD compared with relatives of comparison subjects. For relatives of community subjects with OCD, the risk for definite OCD (10.3% versus 5.6%) was 1.6, and the risk for subclinical OCD (15.4% versus 4.1%) was 3.4 compared with relatives of OCD patients from treatment sites. CONCLUSIONS: These results from the first controlled European family study of OCD confirm earlier U.S. data on the familiality of OCD in patients recruited from treatment facilities. The finding of a comparable familial aggregation of definite OCD and a higher familial aggregation of subclinical OCD in relatives of never-treated persons with OCD from the community strongly supports the impact of familial-genetic factors in OCD.

Ambulatory Care↗

PubMed2006

The German Research Network on Schizophrenia--impact on the management of schizophrenia.

The German Research Network On Schizophrenia (GRNS) is a nationwide network currently comprising 16 psychiatric university departments and 14 state and district hospitals, as well as six local networks of psychiatric practices and general practitioners collaborating on about 25 interrelated, multicenter projects on schizophrenia research. The GRNS aims to intensify collaboration and knowledge exchange between leading research institutions and qualified routine care facilities, both within (horizontal network) and between (vertical network) the two levels of research and care, in order to create the scientific preconditions for optimization of the management of schizophrenia. The concept and the first results of studies aiming at the investigation of (i) strategies for early detection and early intervention in the prodromal stage of psychosis; (ii) treatment in first-episode schizophrenia; (iii) quality management; and (iv) destigmatization, are described as examples of this effort.

Cognition Disorders↗

PubMed2005

Subjective quality of life in subjects at risk for a first episode of psychosis: a comparison with first episode schizophrenia patients and healthy controls.

The concept of quality of life (QoL) is of growing relevance in schizophrenia research. However, there is to date no information on subjective QoL in subjects at risk for a first episode of psychosis in comparison to first episode schizophrenia patients (FE) or healthy controls (HC). Therefore 45 subjects in a putatively early initial prodromal state (EIPS), 40 FE and 45 HC were assessed on demographics, symptoms and subjective QoL as measured by the Modular System for Quality of Life. Results indicated that in most areas HC experienced the highest QoL scores followed in hierarchical order by EIPS and FE. EIPS and FE experienced significantly lower QoL than HC in 5 and 6 of 7 QoL domains. EIPS experienced the lowest ratings in affective QoL. Thus the data demonstrates that subjective QoL in subjects at risk for a first episode of psychosis is substantially reduced when compared with HC and suggests that subjective QoL is already compromised prior to the onset of first positive schizophrenia symptoms. These findings support the notion that subjects at risk for a first episode of psychosis constitute a clinical population for which further service and intervention research is indicated.

Adolescent↗

PubMed2005

Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia.

BACKGROUND: Mismatch negativity (MMN) specifically the response to tone duration deviants has consistently been shown to be reduced in schizophrenia suggesting dysfunction in auditory sensory memory. As part of a multidimensional approach to the early recognition of psychosis, MMN was investigated as a possible risk factor for later development of psychosis in subjects with a prodromal syndrome. Forty-three prodromal subjects, 31 neuroleptic-free inpatients with schizophrenia and 33 healthy controls were studied. A prodromal state was defined by a cluster 'Cognitive Disturbances' as defined by the 'Bonn Scale for the Assessment of Basic Symptoms' (BSABS), which was found highly predictive of first-episode schizophrenia. To elicit MMN, a three-tone auditory oddball paradigm with 10% 'duration deviants' and 10% 'frequency deviants' was used. RESULTS: MMN amplitudes to tone duration deviants were significantly reduced in the patients with schizophrenia compared to controls. The putatively prodromal subjects also showed a slight, though non-significant reduction of the MMN amplitude that was intermediate between normal controls and patients with schizophrenia, and with a larger within-group variance. CONCLUSION: These results support the view that abnormalities in temporal processing are particularly pronounced in patients with schizophrenia. Prodromal subjects are a heterogeneous group with regard to outcome and time until transition to a first psychotic episode. Follow-up of these putatively prodromal subjects will show whether MMN amplitudes further reduce over time in those developing psychosis and if a reduction is state-dependent.

Acoustic Stimulation↗

PubMed2005

Pharmacological intervention in the initial prodromal phase of psychosis.

Early identification and treatment of schizophrenia may alleviate the symptoms, delay the onset and improve the outcome of psychosis. Thus, detection of individuals at risk during the prodromal phase is an important task. Universal approaches to screen the general population or healthy subjects at risk have not proven possible to-date. However, clinical criteria for detecting ultra-high risk individuals have been developed for specialized settings, with their implementation in interventional studies. This article examines the rationale for early detection and intervention of psychosis, along with a review of some of the current studies. These target prevention using psychological and/or pharmacological intervention strategies have demonstrated promising results in high risk individuals. The German Research Network on Schizophrenia (GRNS) is conducting two multicenter early intervention studies; one with early psychological intervention in subjects who manifest early prodromal symptoms; with the second trial applying clinical management and pharmacological early intervention in subjects experiencing late prodromal symptoms (high risk subjects). Despite the promising results, many of the current studies have small sample sizes with study durations of a short period. The full benefits of early detection and intervention should be revealed once larger and longer studies are conducted.

Disease Progression↗

PubMed2005

Neural correlates of visuo-spatial attention during an antisaccade task in schizophrenia: an ERP study.

The authors investigated the role of visuo-spatial attention in an antisaccade task using event-related potentials (ERPs) in schizophrenia patients compared to healthy controls. ERPs between 80-130 ms (P100) after stimulus onset showed differences between pro- and antisaccades only for controls and can be related to the suppression of irrelevant stimulus features. Between 150-180 ms (N100), a larger amplitude for anti-compared to prosaccades over centroparietal electrodes showed that processes of visuo-spatial attention seem to be engaged in performance of the antisaccade task. Left temporo-occipitally, this activity was only evident in schizophrenia patients, possibly reflecting additional neuronal recruitment in order to perform the antisaccade task successfully.

Adult↗

PubMed2005

Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment.

BACKGROUND: The Early Detection and Intervention Programme of the German Research Network on Schizophrenia (GRNS) investigates the initial prodromal phase of psychosis in a multidimensional approach. Two intervention strategies are being studied by two large-scale multicentre projects. AIMS: To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure. METHOD: Comprehensive cognitive-behavioural therapy has been developed for patients in the "early initial prodromal state". For patients in the "late initial prodromal state" the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition. RESULTS: Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48.5%) gave informed consent to participate in the trials. CONCLUSIONS: The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis.

Cognitive Behavioral Therapy↗

PubMed2005

The European Prediction of Psychosis Study (EPOS): integrating early recognition and intervention in Europe.

This paper provides the rationale and design of the European Prediction of Psychosis Study (EPOS), the first European prospective transnational field study of the prodrome and moderating risk/resilience factors of psychosis. As different health systems provide different structures of care, prevention programmes will only be successfully implemented and sustained system-wide, if they can be adapted to the system's special opportunities and needs. EPOS will provide a sound data base for a future evidence-based prevention of psychosis. Data on the recruitment of subjects and on the distribution of the four clinical criteria for an at-risk mental state for psychosis are given.

Journal Article↗

PubMed2004

Evidence for a dysfunctional retrosplenial cortex in patients with schizophrenia: a functional magnetic resonance imaging study with a semantic-perceptual contrast.

We investigated whether the retrosplenial and the posterior cingulate cortex (RS-PCC) is functionally impaired in schizophrenia patients. Therefore, we measured functional magnetic resonance imaging (fMRI) signal changes associated with a synonym-judgment task known to activate, among other areas, the RS-PCC. Compared to 12 matched control subjects, 12 schizophrenia patients exhibited reliably weaker activations in the RS-PCC, the dorsolateral prefrontal cortex and the left orbitofrontal cortex (P < 0.05, corrected). Differences in frontal activations are in line with previous studies showing a structurally and functionally affected prefrontal cortex in schizophrenia. The impaired RS-PCC functionality in a semantic task may relate to verbal memory deficits frequently observed in schizophrenia patients, because this region is pivotal for gating information into the medial temporal lobe memory system.

Brain Mapping↗

PubMed2004

Early detection and secondary prevention of psychosis: facts and visions.

As effective and practical approaches to primary and universal prevention of psychosis are lacking, intervention efforts are targeted at the early stages of schizophrenia to prevent (by way of secondary prevention) or postpone psychosis onset, reduce severity of illness or at least ameliorate the social consequences involved. Early intervention requires early detection and early recognition (diagnosis) of persons at risk and early prediction of psychosis. Within the German Research Network on Schizophrenia (GRNS) awareness programmes are being carried out in several German cities, and these efforts are already improving utilisation of early-recognition and early-prediction services by at risk persons. The empirical basis of developing a two-step early-recognition inventory and strategies of application will be discussed. This instrument is supplemented by a set of cognitive tests, prospectively validated in the GRNS. Results from preliminary analysis of data covering a two-year period demonstrate that the inventory and the cognitive tests are readily accepted. When used for screening in non-specialist settings and at the next level, i. e. at early-recognition centres, they seem to permit identification of at-risk persons. Early intervention is being tested 1) in a randomised controlled multi-centre trial consisting of a specially developed cognitive-behavioural therapy in the early (prepsychotic) prodromal state and 2) on additional treatment with appropriate doses of amisulpride in the late prodromal (early psychotic) state. Preliminary data from Study 1 covering 16.3 months show significantly fewer transitions to psychosis and from Study 2 reduced positive and negative symptoms and improved global functioning compared with controls who had received normal clinical treatment. As a result, both the early-recognition inventory plus cognitive tests and the two therapy strategies are feasible. We hope that the favourable trend indicated by the preliminary data will be confirmed in the final analysis planned for 2005 and the objective of implementing effective and practical secondary prevention of psychosis and its consequences will be attained.

Animals↗

PubMed2004

Neural correlates of temporal context discrimination.

This study investigated event-related potential (ERP) effects when judgments about temporal context (recency judgments) required the retrieval of different amount of information. Subjects studied two consecutively presented word lists and at test made recency judgments to word pairs composed of two previously studied words, one drawn from each list ('Old + Old different' pairs), both drawn from the same list ('Old + Old same' pairs), or two unstudied words ('New + New' pairs). A frontopolar old/new effect was elicited by correct recency judgments which did not differ between both 'Old + Old' pairs. This finding suggests that the generators of the frontopolar old/new effect are not sensitive to the differing retrieval demands required here. However, an old/new effect over left inferior temporal electrodes was larger for 'Old + Old same' than for 'Old + Old different' pairs. The significance of these old/new effects are discussed in relation to the broader pattern of old/new effects seen in standard tests of declarative memory retrieval.

Adult↗

PubMed2003

Dimensions of working memory dysfunction in schizophrenia.

The aim of this study was to investigate the underlying structure of eight working memory tests used to assess prefrontal dysfunction in schizophrenia research [Letter-Number Span (LNS), Digit-Symbol Test (DST), Trail-Making Test B (TMT-B), Delayed Response Task (DRT) for spatial working memory, Subject Ordered Pointing Task (SOPT), Dual Tasking (DUAL), Continuous Performance Test (CPT)-Identical Pairs, Wisconsin Card Sorting Test (WCST)]. Sixty-six patients with schizophrenia showed significant working memory performance deficits in all tests when compared with 45 healthy controls. Performance was not systematically related to psychopathology. When differences in IQ were controlled, working memory deficits remained stable except in the WCST. Principal components analyses yielded three components for healthy controls: a comparator function of the central executive defined by a comparison of working memory content with information from the environment, an allocation of attentional resources function, and a maximum storage capacity function. The comparator and maximum storage functions could be replicated in the schizophrenia sample. However, the allocation function did not emerge as an independent component and was replaced by a component defined by the WCST. These findings suggest that working memory is not a unitary concept but rather should be conceptually differentiated as functions of transient storage/active rehearsal capacity and central executive manipulation supporting a previous suggestion proposed by Perry et al. [Schizophr. Bull. 27 (2001) 157].

Adult↗