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In the mink industry, feed costs are the largest variable expense and breeding for feed efficient animals is warranted. Implementation of selection for feed efficiency must consider the relationships between feed efficiency and the current selection traits BW and litter size. Often, feed intake (FI) is recorded on a cage with a male and a female and there is sexual dimorphism that needs to be accounted for. Study aims were to (1) model group recorded FI accounting for sexual dimorphism, (2) derive genetic residual feed intake (RFI) as a measure of feed efficiency, (3) examine the relationship between feed efficiency and BW in males (BWM) and females (BWF) and litter size at day 21 after whelping (LS21) in Danish brown mink and (4) investigate direct and correlated response to selection on each trait of interest. Feed intake records from 9574 cages, BW records on 16 782 males and 16 875 females and LS21 records on 6446 yearling females were used for analysis. Genetic parameters for FI, BWM, BWF and LS21 were obtained using a multivariate animal model, yielding sex-specific additive genetic variances for FI and BW to account for sexual dimorphism. The analysis was performed in a Bayesian setting using Gibbs sampling, and genetic RFI was obtained from the conditional distribution of FI given BW using genetic regression coefficients. Responses to single trait selection were defined as the posterior distribution of genetic superiority of the top 10% of animals after conditioning on the genetic trends. The heritabilities ranged from 0.13 for RFI in females and LS21 to 0.59 for BWF. Genetic correlations between BW in both sexes and LS21 and FI in both sexes were unfavorable, and single trait selection on BW in either sex showed increased FI in both sexes and reduced litter size. Due to the definition of RFI and high genetic correlation between BWM and BWF, selection on RFI did not significantly alter BW. In addition, selection on RFI in either sex did not affect LS21. Genetic correlation between sexes for FI and BW was high but significantly lower than unity. The high correlations across sex allowed for selection on standardized averages of animals’ breeding values (BVs) for RFI, FI and BW, which yielded selection responses approximately equal to the responses obtained using the sex-specific BVs. The results illustrate the possibility of selecting against RFI in mink with no negative effects on BW and litter size.
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.
Long-term lithium-treatment has been associated with deficits in several cognitive domains in euthymic bipolar patients. At the same time, long-term lithium treatment is also associated with an increase in parathyroid levels, often without a concomitant increase in calcium levels. Such an isolated increase in parathyroid levels has been linked to depressive symptoms and cognitive deficits in otherwise healthy individuals.
To investigate whether increased parathyroid levels are associated with cognitive deficits in euthymic bipolar patients.
We plan to recruit 30 euthymic bipolar patients on lithium treatment for this study. Patients will take part in several neuropsychological tests, covering executive functioning, memory and attention. In parallel, blood levels of lithium, parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium and phosphate will be assessed, besides clinical chemistry and blood cell count. In addition, to account for potential confounders, a variety of clinical variables will be recorded, including established mood rating scales and demographic variables as well as further parameters relevant to the course of the illness.
As the study is still ongoing results are not available yet at this moment.
Results will be discussed in the context of previous studies examining the impact of lithium and parathyroid hormone on mood and cognition in healthy individuals and patients with bipolar disorder, respectively. Dependent on the outcome of this study, potential future studies, including intervention trials aiming at lowering increased PTH levels in bipolar patients on lithium will be outlined.
The effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy resistant major depression and schizophrenia has been shown for all age groups. Nevertheless, age specific side effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients.
We retrospectively evaluated 4457 treatments in 380 patients. Clinical variables, treatment modalities, ictal and postictal neurophysiological parameters were analysed. For modelling the influence of age on these varibles of interest, linear regression models, if necessary logistic regression models, were performed (statistical software package R 2.8.1).
We found a considerable clinical improvement over all age groups. Higher severity of disease at admission came up with a better clinical response. In comparison of the whole patient sample versus the elderly over the age of 60, there were no significant differences in need and number of concomitant psychotropic, but in medical co-medication. Ictal and postictal EEG parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Cardiovascular side effects and cognitive disturbances were more frequent in the elderly but were only transient, and in most cases there was no need for any specific treatment.
The outcome results show excellent effectiveness and tolerability of ECT in all age groups. The very old are more prone to adverse events, but nonetheless tolerate ECT well and are likely to benefit.
Body dysmorphic disorder (BDD) is characterized by a preoccupation with misperceived defects in appearance. Neuropsychological studies and neuroimaging studies of face perception suggests visual processing abnormalities in individuals with BDD, which may involve focus on details at the expense of configural elements.
The objective of the current functional magnetic resonance imaging (fMRI) study was to determine whether individuals with BDD have abnormal patterns of brain activation when visually processing non-face objects (houses).
Fourteen medication-free subjects with BDD and fourteen matched healthy controls engaged in a matching task of photographs of houses that were
b) high spatial frequency (high detail elements only), or
c) low spatial frequency (low detail elements only).
The main outcome measure was group differences in blood oxygen level-dependent fMRI signal changes.
BDD subjects demonstrated lesser activity relative to controls in left parahippocampal gyrus, left lingual gyrus, and bilateral precuneus for low spatial frequency images and relatively greater activity in the frontal pole, left superior frontal gyrus, bilateral anterior cingulate gyrus, and bilateral paracingulate gyrus for high spatial frequency images (Figure 1).
Individuals with BDD have abnormal brain activation patterns when viewing houses for both detailed and configural/holistic visual elements. These results suggest general abnormalities in higher- and lower-order visual processing in individuals with BDD, beyond that for appearance-related stimuli.
To investigate the association of early improvement and treatment emergent suicidal ideation in a large sample (N=705) of naturalistically treated inpatients with major depressive disorder
In line with previous reports early improvement was defined as a 20% HAMD improvement within the first two weeks of antidepressant treatment. Treatment emergent suicidal ideation was defined by a sudden increase from 0 or 1 to at least 3 on HAM-D item-3 and from 0,1 to at least 4 on MADR item 10 for suicidal ideation. Early improvers were compared with non-early improvers with respect to the occurrence of treatment emergent suicidality during treatment.
Early improvers were 3 (MADRS) to 3.4 (HAMD) times less likely to experience new emergence of suicidal ideation during the treatment course than non-improvers. In addition, early improvement was associated with significantly less pessimistic thoughts.
The analysis is based on secondary analysis of prospectively collected data. No controlled study design.
Early improvement is associated with significantly less treatment emergent suicidal ideation for it my may provide rapid symptom relief and reduce hopelessness.
Atypical features are common among depressed primary care patients, but clinical trials testing the efficacy of psychopharmacological and/or psychotherapeutic treatment are lacking. This paper examines the efficacy of sertraline and cognitive behavioural therapy (CBT) among depressed patients with atypical features.
Analyses involve a double-blind comparison of sertraline versus placebo (N=47) and a single-blind comparison between CBT versus a guided self-help group (GSG) (N=48), with primary efficacy endpoints being the Inventory of Depressive Symptomatology (IDSC) and Hamilton Depression Scale (HAMD-17).
In intent-to-treat (ITT) analyses, the decrease on the IDSC scale (and HAMD-17) was greater after CBT compared to GSG: p=0.01 (HAMD-17: p=0.01). The difference between SSRI versus placebo was not significant: p=0.22 (HAMD-17: p=0.36). At endpoint, the CBT versus GSG difference in mean change from baseline IDSc scores was 7.69 points (HAMD-17: 4.97 points), the sertraline versus placebo difference was 3.07 points (HAMD-17: 0.59 points).
The data provide a preliminary suggestion that the mix of patients with minor or mild major depression with atypical features may not be best treated with an SSRI, but that these conditions might be amenable to CBT. Although SSRI were not superior to placebo, it would be premature to rule out SSRI as efficacious in atypical depression.
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.
The increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were mahed for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in ouome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.
Relapse is one of the key factors in the long-term outcome of schizophrenia. The consequences of relapse are diverse and often unpredictable, and the time to recovery and degree of recovery worsen with each successive relapse. There is now overwhelming evidence that advances in antipsychotic drug treatment have led to significant reductions in the rate of relapse. This review charts the developments that have taken place in antipsychotic therapy from the introduction of depot formulations, through atypical agents, to the development of the first long-acting atypical antipsychotic. Depot formulations of conventional antipsychotics were developed in the 1960s and led to fewer relapses and episodes of hospitalization, compared with oral equivalents. Meta-analysis has confirmed that patients receiving depot antipsychotics experience significantly greater global improvement than those receiving the respective oral agents. Conventional antipsychotics are, however, associated with a range of potentially serious adverse events. The atypical antipsychotics were introduced in the 1990s and have significant advantages over conventional agents with regard to positive and negative symptoms. There is also evidence that atypical agents can reduce the risk of relapse. Importantly, atypical antipsychotics have an improved safety profile compared with older agents, particularly with regard to extrapyramidal symptoms. One disadvantage of atypical agents has been that they are only available in an oral form. The recent development of a long-acting injectable formulation of risperidone means that a new treatment option is available to physicians.
This position statement will address in an evidence-based approach some of the important issues and controversies of current drug treatment of depression such as the efficacy of antidepressants, their effect on suicidality, their place in a complex psychiatric treatment strategy including psychotherapy.
The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5–7 for acute treatment and 4 for maintenance treatment. Monotherapy with one drug is often not sufficient but has to be followed by other antidepressants or by comedication/augmentation therapy approaches.
Generally antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk-benefit relationship of treatment with antidepressants can be judged as favourable also in this respect.
The capacity of psychiatrists to individualise and optimise treatment decisions in terms of ‘the right drug/treatment for the right patient’ is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome.
The ideal that all steps of clinical decision making can be based on evidence-based medicine is far away from reality. Clinical experience still has a great impact.
People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement with the aim of improving the care of patients suffering from severe mental illness. The intention is to initiate cooperation and shared care between the different healthcare professionals and to increase the awareness of psychiatrists and primary care physicians caring for patients with severe mental illness to screen and treat cardiovascular risk factors and diabetes.
The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls the neurotransmitter release from the vesicles of the presynaptic neuron into the synaptic cleft. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder.
38 patients with schizophrenia, bipolar disorder or obsessive-compulsive disorder and 15 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped.
Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of NAA/Cho in the left hippocampus compared to the group of individuals with the homozygous TT genotype.
The present findings are consistent with the view that the SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and that an altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.
TDCS for modulating neurophysiology is known since the 1960s. tDCS trials in patients with depression showed promising results.
22 patients with therapy resistant major depression (DSM-IV criteria) were included in a four week cross-over trial, 10 received 1 mA tDCS, 12 received 2 mA tDCS, 2 dropped out. Patients received add-on tDCS under a stable antidepressant treatment over 3 weeks and were randomized to active or sham tDCS treatment. The sham condition was evaluated in 10 healthy volunteers and was indistinguishable.Both, active (1 mA resp. 2 mA) and placebo tDCS were applied for 20 min per day and for two weeks and then switched to the other condition. The anode was positioned over F3 and the cathode over the contralateral supraorbital region. For placebo tDCS a novel sham device (neuroConn, llmenau, Germany) was used which is indistinguishable for the applying person. Severity of depression was assessed by HAMD, BDI, CGI and CORE scales and raters were blind to treatment conditions.
Mean HAMD decreased by 25% in the whole population after four weeks of tDCS. Active tDCS performed significantly better (p = 0.0492) than the control treatment. However this positive association was restricted to the first study phase as there was also a significant (p = 0.0271) influence of the study phase in the cross-over design and an almost significant (p = 0.0864) interaction between treatment and study phase.
Though active tDCS was not superior to sham treatment, we observed hangover effects in weeks 3 and 4 depending on the first condition.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.