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Although well researched and praised in academic publications, function modelling (FM) does not have gained much traction in industrial application. To investigate into possible reasons for this, this publication researches literature of nine different projects where enhanced function-means modelling has been applied. The projects are analysed for their purpose of FM-use, applied benefits and discovered challenges of the FM approach. From this, the main challenges for FM application are the abstraction level of the modelling language as well as the lack of an interface to CAD modelling.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Until now, no studies have been published about the prevalence and needs of children with a mentally ill parent nor about interventions for this vulnerable group in the federal state of Saxony, Germany.
Therefore, the multi-centre study HELP-S for Children was initiated by the University of Leipzig in cooperation with the Technical University of Dresden. The aim of HELP-S for Children is to identifiy the prevalence and specific needs of children with a mentally ill parent.
All psychiatric outpatients of Leipzig and Dresden at an appointed date will be asked to participate in the study. Patients with minor children will be asked to fill out a detailed questionnaire about the perceived needs of their children and the existing and lacking support possibilities. Because there is no adequate instrument to assess the needs of the children with a mentally ill parent, we will develop a standardized questionnaire by using expert interviews and a pre-test with mentally ill parents.
The standardized questionnaire, which we will develop for this study, will be useable in other studies about needs of children with a mentally ill parent. Furthermore, we will gather information about the prevalence of children of mentally ill parents who are outpatients and about the specific needs of these children in the age of 0 to 18. These results will be presented and discussed during an expert workshop at the end of the project to explore ways to improve the situation of children with a mentally ill parent.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
Demographical and clinical characteristics have been reported to modulate the risk for suicide. This study analysed demographical and clinical characteristics with respect to lifetime suicide attempts in 500 individuals affected with schizophrenic or affective disorders. Suicide attempts were associated with poor premorbid social adjustment, low age at onset, low scores on the “Global Assessment Scale” and childlessness in females.
26.5% of psychiatric patients in Germany have minor children. More than half of these children have specific needs, which are seldom met.
To examine problems, needs and used interventions for families with a mentally ill parent in the federal state of Saxony, Germany. The study focused on outpatients and included mothers and fathers and all psychiatric disorders.
We asked all psychiatrists in the federal state of Saxony to take part in our study. All patients with minor children who came to one of the 58 participating psychiatrist's practices at an appointed date were asked to fill out a detailed questionnaire including sociodemographic data, the Strengths and Difficulties Questionnaire (SDQ), specific needs, used interventions and reasons for not using interventions. The questionnaire was developed using data from 26 expert interviews.
128 psychiatric outpatients took part in our study (78% female). The most common diagnoses were depression and anxiety disorders. More than 40% of the patients rated their children in the SDQ in an abnormal or borderline range. 22% of the children have been treated because of emotional or behavioural problems. Reasons not to use interventions were missing knowledge and fear of stigmatisation.
HELP-S for children is the first study which examines the situation of children with a mentally ill parent in an outpatient setting. Therefore, our results are an improvement in research in the field of families with a mentally ill parent and heading towards the improvement of care.
Affective symptomatology has repeatedly been suggested to confer susceptibility to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history of depressive symptoms was not associated with the occurrence of TD, whereas manic symptomatology was significantly associated with the absence of TD. Thus, our data suggest that affective symptomatology cannot unambiguously be considered to predispose to TD.
Face processing is crucial for social interaction, but impaired in schizophrenia in terms of delays and misperceptions of identity and affective content. One important functional region for early stages of human face processing is the right fusiform face area. Thus, this region might be affected in schizophrenia. Aim of the study was to investigate whether face processing deficits are related to dysfunctions of the right fusiform face area in schizophrenics compared to controls.
In a rapid event-related fMRI design encoding of new faces as well as the recognition of newly learned, famous, and unknown faces was investigated in 13 schizophrenics and 21 healthy controls. Region of interest analysis was applied to each individual's right fusiform face area and tested for group differences.
Controls displayed more BOLD activation during the memorization of faces that were later successfully recognized. In schizophrenics this effect was not present. During the recognition task schizophrenics had lower BOLD responses, less accuracy, as well as longer reaction times to famous and unknown faces.
Our results support the hypothesis that impaired face processing in schizophrenia is related to early stage deficits during the encoding and immediate recognition of faces.
Motor symptoms are frequent in patients with schizophrenia. Although recent DTI studies point to white matter alterations of the motor system in schizophrenia little is known about specific changes.
To date there is a lack of approaches with hypothesis driven quantification of specific anatomical fibre tracts. Therefore, we aimed to compare structural connectivity between specific parts of the motor system such as the pre-supplementary motor area (SMA), the SMA-proper, the primary motor cortex and the basal ganglia in patients with schizophrenia and in healthy controls in a DTI-fibre-tracking study.
It is the aim of this study to investigate whether fibre tract integrity of the motor system is altered in patients with schizophrenia.
DTI-data were measured in 21 patients with schizophrenia and in 21 healthy controls. Applying a probabilistic fibre tracking approach the most probable anatomical pathways between key regions of the motor system of each participant have been identified. The resulting probabilistic maps were normalized to obtain values between 0 and 1, normalized into the standard MNI-space and smoothed using an isotropic 3-mm Gaussian kernel. Group comparisons have been calculated using two-sample-t-tests.
First results point to altered fibre tract microstructure of loops including cortical motor areas and the basal ganglia. The data analysis is preliminary. Definite results will be presented at the conference.
Altered motor behaviour might be reflected by altered white matter integrity of loops including cortical motor areas and the basal ganglia.
Preclinical and first clinical studies suggested that the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen might be effective in the treatment of alcohol dependence. However, previous randomized controlled trials have reported inconsistent results, possibly related to the low to medium dosages of baclofen used in these studies.
To assess the efficacy and safety of individually titrated high-dose baclofen (30-270 mg/d) for the treatment of alcohol dependence.
Fifty-six alcohol-dependent patients were randomized to a double-blind treatment with individually titrated baclofen or placebo. Multiple primary outcome measures were total abstinence and cumulative abstinence duration during a 12-week high-dose phase.
Preliminary results of this clinical trial will be presented.
Brain-derived neurotrophic factor (BDNF) plays important roles in neurotransmitter release and synaptic plasticity and has been hypothesized to be involved in the development and maintenance of addictive disorders. Also, alterations in secretion of stress hormones within the <a name="_Hlk388856744">hypothalamic–pituitary–adrenal </a>(HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might modulate behavioural responses to substances of abuse. Therefore, we investigated alterations of BDNF expression and HPA axis activity in non-substance-related addictive disorders, i.e. pathological gambling (PG) and Internet use disorder (IUD).
We measured serum BDNF levels, plasma levels of copeptin, a vasopressin (AVP) surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with PG (n=14), IUD (n=11) and carefully matched healthy controls for PG (n=13) and IUD (n=10).
BDNF serum levels were significantly increased in patients with PG in comparison to healthy control subjects (p = 0.016). Furthermore, cortisol plasma levels correlated negatively with the PG-YBOCS total severity score (r<sup>2</sup> = -.626, p = .039) in patients with PG. There was no significant difference in BDNF serum levels of patients with IUD in comparison to control subjects. Plasma levels of copeptin, ACTH and cortisol in patients with PG and IUD did not differ among groups.
These preliminary results might suggest that the pathophysiology of PG shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in IUD.
Visual perception is a very important source of information about the human social environment. Gaze behavior reflects the perceptive processes during guided collection of data relevant for social cognition.
Gaze behavior in subjects clinically at high risk of psychosis (CHR) and in schizophrenia patients (SZ).
Investigating the relationship between gaze behavior and social functioning.
CHR, SZ and healthy control (HC) subjects were asked to assess the emotional qualities (positive, negative, neutral) of faces. Visual scan paths were recorded with an SMI iView X™ Hi-Speed System (500 Hz). Functioning was assessed by two scales introduced by Cornblatt et al. (2007).
Scan path parameters differed significantly between HC and SZ as well as CHR. Functioning was lower in both patient groups and correlated with gaze behavior.
Gaze behavior is already aberrant in risk states of psychosis and seems to have a significant impact on social functioning.