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Biomedical subjects

Joachim Klosterkötter

Publications and source records attributed to Joachim Klosterkötter.

At least 19 recordsLinked to original sources
PubMed2006

Determination of anandamide and other fatty acyl ethanolamides in human serum by electrospray tandem mass spectrometry.

We developed a new selective liquid chromatography-electrospray ionization-tandem mass spectrometry method for the identification and quantification of anandamide (AEA), an endogenous cannabinoid receptor ligand, and other bioactive fatty acid ethanolamides (FAEs) in biological samples. Detection limit (0.025 pmol for AEA and 0.1 pmol for palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)) and quantification limit (0.2 pmol for AEA and 0.4 pmol for OEA and PEA) were in the high fmol to low pmol range for all analytes. Linear correlations (r(2)=0.99) were observed in the calibration curves for standard AEA over the range of 0.025-25 pmol and for standard PEA and OEA over the range of 0.1-500 pmol. This method provides a time-saving and sensitive alternative to existing methods for the analysis of FAEs in biological samples.

Amides↗
PubMed2006

Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

Acute Disease↗
PubMed2006

Recent approaches to psychological interventions for people at risk of psychosis.

With the emerging global focus on early psychosis, indicated prevention in schizophrenia has increasingly become a focus of psychiatric research interests. It has been argued that CBT may have some advantages compared with antipsychotics regarding this issue. According to MEDLINE, EMBASE and Psycinfo two completed randomised controlled trials (RCTs; PACE, Melbourne, Australia; EDIE, Manchester, United Kingdom) and one ongoing RCT with only preliminary results published so far (FETZ, Cologne/Bonn, Germany) on indicated prevention in schizophrenia including manualised and standardised psychological treatment can be identified. The aims of the present paper are to present and discuss the three approaches with regard to (I) inclusion, exclusion and exit criteria, (II) characteristics of interventions and (III) evaluations. All interventions use intake, exclusion and exit criteria, which have been evaluated in prospective follow-along studies. The approaches are based on the general structure and principles of cognitive behavioural therapy which have been developed, applied and evaluated in a wide range of mental health problems. Despite several methodological limitations, the first evaluations indicate some effects with regard to three possible aims of early intervention: (1) improvement of present possible pre-psychotic symptoms, (2) prevention of social decline/stagnation and (3) prevention or delay of progression to psychosis. Even though the first results are promising, we conclude that several ethical issues have to be taken into consideration and further predictive and therapeutic research is needed to judge whether psychological intervention is a realistic option for the treatment of people at risk of psychosis.

Adaptation, Psychological↗
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

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

Cognitive-behavioral therapy in the pre-psychotic phase: an exploratory study.

Although the efficacy of cognitive-behavioral therapy (CBT) in schizophrenia has been established for persistent psychotic symptoms, little information is available on the effects of CBT in the pre-psychotic phase. We developed a comprehensive CBT program for clients in the early initial prodromal state that showed good feasibility and promising treatment effects in an uncontrolled prospective study. The specificity of these effects needs to be explored in a controlled trial.

Adult↗
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

Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities.

BACKGROUND: Clinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness. AIMS: To describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder. METHOD: Strategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided. RESULTS: Well-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made. CONCLUSIONS: The detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.

Adolescent↗
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

Antibodies to infectious agents in individuals with recent onset schizophrenia.

We investigated the levels of antibodies to infectious agents in the serum and cerebral spinal fluids (CSFs) of individuals with recent onset schizophrenia and compared these levels to those of controls without psychiatric disease. We found that untreated individuals with recent onset schizophrenia had significantly increased levels of serum and CSF IgG antibody to cytomegalovirus and Toxoplasma gondii as compared to controls. The levels of serum IgM class antibodies to these agents were not increased. Untreated individuals with recent onset schizophrenia also had significantly lower levels of serum antibody to human herpesvirus type 6 and varicella zoster virus as compared to controls. Levels of antibodies to herpes simplex virus type 1, herpes simplex virus type 2, and Epstein Barr virus, and did not differ from cases and controls. We also found that treatment status had a major effect on the levels of antibodies in this population. Individuals who were receiving treatment had lower levels of antibodies to cytomegalovirus and Toxoplasma gondii, and higher levels of serum antibodies to human herpesvirus type 6 as compared to untreated individuals. The level of antibodies to Toxoplasma and human herpesvirus type 6 measured in treated individuals did not differ from the levels measured in controls. In the case of cytomegalovirus, the levels of CSF antibodies in treated individuals did not differ from those of controls, while the level of serum IgG antibodies to CMV remained slightly greater than controls in this population. Our studies indicate that untreated individuals with recent onset schizophrenia have altered levels of antibodies to cytomegalovirus, Toxoplasma gondii, and human herpesvirus type 6 while the levels of these antibodies in treated individuals with recent onset schizophrenia are similar to those of controls. These findings indicate that infectious agents may play a role in the etiopathogenesis of some cases of schizophrenia.

Adult↗
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↗