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.

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.

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.

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.

[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.

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.

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.

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.

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.

Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells.

The insulin responsive H4IIEC3 rat hepatoma cell line (H4 cells) was used in order to determine the role of the transcription factor FKHR in the regulation of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Both PEPCK and G6Pase contain putative FKHR binding sites in their promoter sequence. Using a retroviral expression system, we stably overexpressed FKHR in H4-cells. FKHR was phosphorylated in a PI 3-kinase- and Akt-dependent manner, and was translocated from the nucleus to the cytoplasm in response to insulin. Furthermore, overexpression of FKHR markedly increased the expression of the catalytic subunit of G6Pase (basal about 2.5-fold, dexamethasone/cAMP stimulated about fivefold, respectively). In contrast, both basal and dexamethasone/cAMP-induced levels of PEPCK mRNA were unaffected by FKHR-overexpression. These data suggest a specific function for FKHR in the regulation of hepatic gluconeogenesis at the level of G6Pase, but not PEPCK gene expression.

Phorbol ester-induced activation of mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase and extracellular-signal-regulated protein kinase decreases glucose-6-phosphatase gene expression.

Glucose-6-phosphatase (G6Pase) plays a central role in blood glucose homoeostasis, and insulin suppresses G6Pase gene expression by the activation of phosphoinositide 3-kinase (PI 3-kinase). Here, we show that the phorbol ester PMA decreases both basal and dexamethasone/cAMP-induced expression of a luciferase gene under the control of the G6Pase promoter in transiently transfected H4IIE hepatoma cells. This regulation was suppressed by the inhibitors of the mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase (MEK), PD98059 and U0126, but not by the inhibitor of PI 3-kinase, LY294002. The co-expression of a constitutively active mutant of MEK mimicked the regulation of G6Pase promoter activity by PMA. The effect of PMA on both basal and induced G6Pase gene transcription was impaired by the overexpression of a dominant negative MEK construct, as well as by the expression of mitogen-activated protein kinase phosphatase-1. The mutation of the forkhead-binding sites within the insulin-response unit of the G6Pase promoter, which decreases the effect of insulin on G6Pase gene expression, did not alter the regulation of gene expression by PMA. The data show that PMA decreases G6Pase gene expression by the activation of MEK and extracellular-signal regulated protein kinase. With that, PMA mimics the effect of insulin on G6Pase gene expression by a different signalling pathway.

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.

Regulation of glucose-6-phosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR. Evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity.

Glucose-6-phosphatase plays an important role in the regulation of hepatic glucose production, and insulin suppresses glucose-6-phosphatase gene expression. Recent studies indicate that protein kinase B and Forkhead proteins contribute to insulin-regulated gene expression in the liver. Here, we examined the role of protein kinase B and Forkhead proteins in mediating effects of insulin on glucose-6-phosphatase promoter activity. Transient transfection studies with reporter gene constructs demonstrate that insulin suppresses both basal and dexamethasone/cAMP-induced activity of the glucose-6-phosphatase promoter in H4IIE hepatoma cells. Both effects are partially mimicked by coexpression of protein kinase Balpha. Coexpression of the Forkhead transcription factor FKHR stimulates the glucose-6-phosphatase promoter activity via interaction with an insulin response unit (IRU), and this activation is suppressed by protein kinase B. Coexpression of a mutated form of FKHR that cannot be phosphorylated by protein kinase B abolishes the regulation of the glucose-6-phosphatase promoter by protein kinase B and disrupts the ability of insulin to regulate the glucose-6-phosphatase promoter via the IRU. Mutation of the insulin response unit of the glucose-6-phosphatase promoter also prevents the regulation of promoter activity by FKHR and protein kinase B but only partially impairs the ability of insulin to suppress both basal and dexamethasone/cAMP-stimulated promoter function. Taken together, these results indicate that signaling by protein kinase B to Forkhead proteins can account for the ability of insulin to regulate glucose-6-phosphatase promoter activity via the IRU and that other mechanisms that are independent of the IRU, protein kinase B, and Forkhead proteins also are important in mediating effects of in insulin on glucose-6-phosphatase gene expression.

[Origins of dialogue: phenomenological theories of intersubjectivity in developmental perspectives and as a foundation of psychotherapeutic processes]. / Ursprünge des Dialogs. Phänomenologische Ansätze zur Intersubjektivität in entwicklungsgeschichtlicher Perspektive und als Grundlage psychotherapeutischer Prozesse.

Recognizing the other with his/her psychic peculiarity is an important assumption for psychotherapy. But how is empathy possible? Answers are to be expected by phenomenological-philosophical approaches concerning intersubjectivity and infant research. They are described in a comprehensive way and related to each other in spite of their epistemological differences. As can be seen in the beginning of showing and reading maternal emotions (so-called "social referencing") an infant is able to show intersubjective behaviour from the age of nine months on. Research on the reflected image of the infant and the development of shame shows that consciousness of the ego is not built before the age of one and a half years. These empirically well established results contradict those phenomenological approaches claiming that the other cannot be experienced directly but via cognitive analogies of own emotions (Lipps, Husserl). They better fit an anthropology that states the human being as an innate dialogically structured one and therefore being capable of empathy. Therefore the base for a deeper understanding of the following results of psychotherapy-research is established: 1. Early infant's memories probably do not exist as isolated images but are embedded in interactional structures. 2. Strict therapeutical abstinence may be experienced as a denial of communication and may have a retraumatic effect. 3. Quality of therapeutical relationship is crucial for the success of psychotherapy.

Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells.

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.

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.