Adverse events of group psychotherapy in the in-patient setting - results of a naturalistic trial.

OBJECTIVE: Adverse events of psychotherapy have often been neglected in research. In this study, potential adverse events of group psychotherapies in a psychiatric hospital were systematically assessed, explored for predictors and linked to treatment outcome. METHOD: A naturalistic trial was conducted in 180 in-patients attending different group psychotherapies. Adverse events were assessed using three different measures: (i) weekly reporting of unwanted treatment reactions, (ii) mood changes in response to every single group session and (iii) premature group termination. RESULTS: Different measures of adverse events were weakly associated. Deterioration of mood state and/or unwanted treatment reactions were experienced by 60-65% of all patients. Reports of unwanted treatment reactions decreased over time and were negatively associated with symptom improvement. However, mood state deterioration was constant and unrelated to treatment outcome. The rate of premature group termination was 34%. Significant predictors of adverse events included patient characteristics as well as disadvantageous group conditions. CONCLUSIONS: For the majority of patients, group psychotherapy in the in-patient setting is associated with adverse events. Changes over time and a strong correlation with general symptom severity must be considered in the assessment and interpretation of adverse events. Predictors should be considered as potential risk factors in future research.

[Decision making, empathy and morality in psychopaths: does empirical research offer new perspectives concerning legal responsibility?]. / Entscheidungsverhalten, Empathiefähigkeit und Moralität bei Psychopathy: Bieten die empirischen Befunde neue Aspekte im Hinblick auf die Beurteilung der Schuldfähigkeit?

Psychopathy is a well explored dimensional construct only partially overlapping with dissocial personality disorder according to ICD-10. Until now, psychopaths have not been assessed as having diminished legal responsibility, unless they show impulsive or dissocial behaviour in an early stage of development, since they are considered able to adapt themselves to social norms. This forensic practice has been criticised from a deterministic-neurobiological point of view. This article discusses whether the latest empirical results on the psychopath's capacity for decision-making, empathy, and morality should lead to a new assessment of legal responsibility. The author shows that the psychopath's reduced capacities for decision-making, response reversal, and emotional empathy do not tell us much about the way such an individual arrives at decisions outside the laboratory since there has been no exploration of how compensation is made for psychophysiological deviation. Studies comparing criminal and non-criminal (so called "successful") psychopaths support the view that single physiological findings such as a hypoarousal do not necessarily lead to criminal behaviour. The moral knowledge of psychopaths is not disturbed. That is why criminality seems to be caused mainly by developed motivational factors (risk-seeking and hedonistic life-style). Empirical research into psychopathy may enlarge our knowledge about pathogenesis but does not offer new perspectives concerning legal responsibility.

Ceruloplasmin expression in rat liver cells is attenuated by insulin: role of FoxO transcription factors.

The phosphoinositide 3'-kinase (PI3 K)/Akt pathway controls the activity of a number of proteins important in the regulation of apoptosis and cell proliferation. FoxO (forkhead box, class O) transcription factors, substrates of the Ser/Thr kinase Akt, control the expression of several target genes that are crucial to the defense against oxidative stress, the regulation of cell cycle, and apoptosis in mammalian cells. Here, expression of ceruloplasmin (CP), the major copper-containing protein in blood released by the liver, was investigated. We observed a significant downregulation of CP mRNA levels after insulin treatment in H4IIE rat hepatoma cells. The PI3K inhibitor wortmannin counteracted this insulin effect on CP mRNA levels, indicating that the PI3K/Akt cascade is involved in the regulation of CP expression. Stimulation of FoxO1 was induced in H4IIE rat hepatoma cells expressing a conditionally active FoxO1 construct, resulting in significant upregulation of CP mRNA levels. This upregulation was prevented in the presence of insulin. In parallel, mRNAs of established FoxO target genes were analyzed: like CP mRNA, selenoprotein P and glucose 6-phosphatase mRNAs were upregulated by FoxO1, which was prevented by insulin. The same effects of insulin on CP mRNA levels were detected in primary rat hepatocytes. Furthermore, CP release into cell culture media was analyzed with primary hepatocytes and found to be attenuated by insulin. In line with its insulin-mimetic effects on cultured cells, Cu (2+) imitated the effect of insulin on CP expression and caused a downregulation of CP mRNA levels in rat hepatoma cells.

Stimulation of fat oxidation, but no sustained reduction of hepatic lipids by prolonged pharmacological inhibition of acetyl CoA carboxylase.

Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat metabolism and their inhibition has been postulated to be beneficial for the treatment of the metabolic syndrome by decreasing ectopic fat accumulation. In order to validate this approach pharmacologically, we characterized the chronic effect of the small molecule ACC1/2 inhibitor SAR210 in 2 rodent models of fatty liver. Chronic administration of SAR210 increased serum ketone levels in both diet-induced obese mice and female ZDF rats. The inhibitor neither reduced hepatic triglycerides nor influenced body weight in either diet-induced obese mice or female ZDF rats. Thus, chronic pharmacological inhibition of ACC1/2 stimulated fat oxidation, which was, however, not sufficient to reduce hepatic triglycerides.

[Delusion of parasitosis due to Wegener's granulomatosis]. / Sekundärer Dermatozoenwahn bei Wegener Granulomatose.

A delusion of parasitosis can be idiopathic or due to different somatic or psychiatric disorders. We report on a 48-year-old man who suffered from imagined animals in his nose. A somatic cause could not be found so that we diagnosed an idiopathic delusion of parasitosis. Later, Wegener's granulomatosis, a rare form of autoimmune induced vasculitis, was diagnosed. It was treated successfully with immunosuppressiva. The psychotic symptoms which remitted under risperidone did not return after finishing the neuroleptic medication.

Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans.

Resveratrol and SRT1720 have been shown to act as sirtuin activators that may ameliorate type 2 diabetes and metabolic diseases in mice. Moreover, resveratrol extends lifespan in model organisms like C. elegans, N. FURZERI, and possibly D. melanogaster. The aim of the study was to test whether pharmacological concentrations of resveratrol and SRT1720 are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. ELEGANS roundworms were maintained on agar plates and fed E. COLI strain OP50 bacteria. Resveratrol (5 micromolar, 500 nanomolar) or SRT1720 (1 micromolar, 100 nanomolar) was applied to the agar to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan). By unexpected contrast, SRT1720, which was previously proposed to be several hundred times more active than resveratrol, did not extend lifespan at none of the concentrations tested. Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses. The sirtuin activator SRT1720 did not extend lifespan, suggesting that in C. elegans, some relevant effects of resveratrol cannot be mimicked by SRT1720.

Glucokinase-activating GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk in the Ludwigshafen Risk and Cardiovascular Health Study.

Two strongly correlated polymorphisms located within the gene of the glucokinase regulator protein (GKRP), rs780094 and rs1260326, are associated with increased plasma triglyceride levels and provide a genetic model for the long-term activation of hepatic glucokinase. Because pharmacological glucokinase activators are evaluated for the treatment of diabetes, the aim of the study was to assess if these polymorphisms could provide evidence for an increased cardiovascular risk of long-term glucokinase activation. Therefore, these polymorphisms were tested in 3 500 patients of the Ludwigshafen Risk and Cardiovascular Health study, which was designed to assess cardiovascular risk factors. The two variants were associated with a significant increase of both plasma triglycerides (p<0.0001) and VLDL triglyceride levels (p<0.0001). Plasma free fatty acid concentrations were also significantly elevated (p<0.0078). LDL and HDL cholesterol levels were unchanged. No association was found with respect to coronary stenosis, myocardial infarction, left ventricular wall hypertrophy, and hypertension. In conclusion, long-term genetic glucokinase activation by the GKRP polymorphisms was not associated with an increased cardiovascular risk in the study population.

[Body dysmorphic disorder]. / Körperdysmorphe Störung.

A survey of the body dysmorphic disorder, once known as "dysmorphophobia", is given concerning classification, symptoms, diagnosis, epidemiology, nosology, pathogenesis and therapy. It can be shown that there is no good reason to differentiate between delusional and non-delusional forms as has been done in the international classification systems. Shame is the common affect that leads into the vicious circle of self-observation and bashfulness. The available data just confirm the clinical impression that we have to deal with a unified syndrome. In addition, actual studies show how important comorbidity is, especially comorbid depressions.

Regulation of glucose-6-phosphatase gene expression by insulin and metformin.

The biguanide derivative metformin is a potent anti-diabetic drug widely used in the treatment of type 2 diabetes mellitus. Its major effect on glucose metabolism consists in the inhibition of hepatic glucose production. Since the mechanisms of metformin action are only partially understood at the molecular level, we studied the regulation of the gene promoter activity of glucose-6-phosphatase (G6Pase), the central hepatic gluconeogenic enzyme, by this drug. We have found that both metformin and insulin inhibit the basal and dexamethasone/cAMP-stimulated G6Pase promoter activity in hepatoma cells. Since one of the pharmacological targets of metformin is AMP-activated protein kinase (AMPK) and activation of AMPK is known to inhibit hepatic glucose production by the suppression of G6Pase gene transcription, we studied the effect of AMPK in this context. Under nonstimulated conditions, the inhibitory effect of both insulin and metformin was partially counteracted to a similar extent by treatment with compound C, a specific inhibitor of AMPK. In contrast, under conditions of stimulation with dexamethasone and cAMP, treatment with compound C reversed the inhibitory effect of metformin on G6Pase promoter activity to a similar extent as compared to nonstimulated conditions, whereas the effect of insulin was almost resistant to treatment with the AMPK-antagonist. These data indicate a differential AMPK-dependent regulation of G6Pase gene expression by insulin and metformin under basal and dexamethasone/cAMP-stimulated conditions.

Basal level glucose-6-phosphatase gene transcription requires binding sites for Sp family proteins within the gene promoter.

The significance of two regions (SpA: -19 to -11 and SpB: -63 to -55) within the human glucose-6-phosphatase (G6Pase) gene promoter for gene expression was examined. The mutation of SpA and SpB together, but not alone, decreased G6Pase promoter activity. Electromobility shift assays showed that SpA and SpB were able to bind the transcription factors Sp1 and Sp3.

Cloning and sequencing of the 5' region of the human glucose-6-phosphatase gene: transcriptional regulation by cAMP, insulin and glucocorticoids in H4IIE hepatoma cells.

We have cloned and sequenced the first 1.2 kb of the 5' region of the human glucose-6-phosphatase gene. Transfection of H4IIE hepatoma cells with the 1.2 kb fragment fused to a luciferase reporter gene demonstrated both basal and hormone responsive luciferase activity. Dexamethasone increased and insulin decreased luciferase activity. Insulin and dibutyryl cyclic AMP both significantly decreased activity in the presence of dexamethasone.

Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an insulinoma cell line (INS-1).

Primer extension analysis and RNase protection assays revealed the identity of glucose 6-phosphatase gene transcripts in both the insulinoma cell line INS-1 and hepatic cells. In transient transfection assays of INS-1 cells, using constructs between the human glucose 6-phosphatase gene promoter and a luciferase reporter gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP. Furthermore, the promoter was regulated by the glucose concentration in the medium. This effect was dependent on glucose metabolism. The data indicated that glucose 6-phosphatase gene transcription is regulated in a similar way in the insulinoma cell line and in liver.

Plasma exchange in chronic progressive multiple sclerosis: a long-term study.

Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.

Chronic progressive multiple sclerosis: double-blind controlled study of plasmapheresis in patients taking immunosuppressive drugs.

Fifty-four patients with chronic progressive multiple sclerosis received prednisone plus oral low-dose cyclophosphamide and either true plasmapheresis (PP) or "sham" PP weekly for 20 weeks in a double-blind controlled study. Immunosuppressive drug therapy alone (sham PP group, n = 29) was associated with improvement (greater than or equal to one step in Kurtzke Disability Status Scale [DSS]; mean change of 1.5) in 8 and stabilization of MS in 18 patients, with this status sustained in 23 patients at follow-up, 11 months after entry. In contrast, 14 of 26 patients who received "true" PP improved (greater than or equal to one step in DSS; mean change of 2.6), and 11 more were stable, with these changes sustained in 23 of 26 patients at follow-up. These differences, overall, between the PP and sham PP groups were significant at p less than 0.007.

Differential expression of the subunits of the glucose-6-phosphatase system in the clear cell type of human renal cell carcinoma - no evidence for an overexpression of protein kinase B.

The expression of two components of the glucose-6-phosphatase system, the catalytic subunit (G6PaseC) and the glucose-6-phosphate transporter, was analyzed in the clear cell type of human renal cell carcinoma. The expression of G6PaseC was decreased in tumours compared with non-tumourous tissue of the same patient. The expression of G6PaseT varied with no general trend between tumours and control tissue. The expression of protein kinase B (PKB) was unchanged in the tumours, suggesting that the down-regulation of G6PaseC in clear cells and the maintenance of the transformed phenotype are not predominantly caused by an overexpression of PKB.

Colocalization of fructose-1,6-bisphosphatase and glial fibrillary acidic protein in rat brain.

Immunofluorescence studies of rat brain sections demonstrated an exclusive colocalization of the gluconeogenic key enzyme fructose-1,6-bisphosphatase (FBPase) with the astroglial marker glial fibrillary acidic protein, indicating FBPase in brain as an astrocyte-specific enzyme. This conclusion was supported by the presence of FBPase activity in astroglia-rich but not neuron-rich primary cultures derived from rat brain.

Expression of thyroid hormone receptor isoform alpha1 in pancreatic islets.

Thyroid hormone receptors (TR) mediate the action of thyroid hormones. Genetic studies revealed that the individual TR isoforms possess different functions. In the present paper we studied the expression of the isoforms TRalpha1 and TRbeta1 in the murine pancreatic islet. TRalpha1 and TRbeta1 mRNA transcripts and proteins were detected in islets using reverse transcription-polymerase chain reaction and Western blotting analyses, respectively. In immunohistochemical studies individual cells in the periphery of islets were labelled using an anti-TRalpha1 antibody. No labelled cells were detected in the exocrine pancreas. A similar staining pattern was obtained with an anti-glucagon antibody, but not with an anti-insulin antibody, which suggests that TRalpha1 is mainly expressed in alpha-cells. In order to address a potential function of TRalpha1 in this cell type, the regulation of glucagon gene expression by triiodothyronine was studied in a glucagon-producing cell line by Northern blot analysis and transient transfection assays using glucagon promoter luciferase fusion gene constructs. In these assays, triiodothyronine did not regulate the glucagon mRNA level or the glucagon promoter activity. The predominant localization of TRalpha1 in pancreatic alpha-cells suggests that this receptor isoform mediates a specific, yet unknown, function of thyroid hormones in this cell type.

[Co-enaesthetic schizophrenia. Case studies of illness perception and compliance]. / Coenästhetische Schizophrenie. Kasuistische Untersuchungen zur Krankheitsbedeutung und Compliance.

Against the background of clinical and anthropological considerations, the case studies of eleven patients with coenaesthetic schizophrenia (F 20.8 in ICD-10) are evaluated with regard to how the patients experience the disorders of corporal perception. Additional criteria for the evaluation are whether the disorders receive a special significance in dealing with the psychosis, and whether they influence compliance with medicinal intake. In two cases, the coenaesthesies were experienced as making the patients happy, they were used by the patients to strengthen themselves, and so the motivation for medicinal therapy was accordingly small. Of the remaining nine patients who suffered from the body perception disorder, five were not willing to accept neuroleptic therapy. The author ascribes this above all to two behaviours: the patients either deny their symptoms, or they attempt to use them to compensate for ego-weakness. However, an effect of self-stabilisation through the coenaesthesies, as measured by social capabilities, is not objectively recognisable.