Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa.

BACKGROUND: Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce. OBJECTIVE: In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response. METHODS: Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation. RESULTS: Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation. CONCLUSIONS: These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception. LEVEL OF EVIDENCE: Level III, case-control study.

How do patients with anorexia nervosa "process" psychotherapy between sessions? A comparison of cognitive-behavioral and psychodynamic interventions.

OBJECTIVE: Patients' processing of psychotherapy between sessions ("inter-session process" (ISP)) has been repeatedly shown to be related to outcome. The aim of this study was to compare ISP characteristics of cognitive-behavioral vs. psychodynamic psychotherapy in the treatment of anorexia nervosa (AN) and their relation to outcome. METHODS: Data of 106 patients participating in a randomized-controlled trial who received either 40 sessions of enhanced cognitive-behavioral therapy (CBT-E) or focal psychodynamic therapy (FPT) were analyzed. The ISP was measured with the Inter-session Experience Questionnaire (IEQ). Three outcome classes were distinguished: full recovery, partial recovery, and still fulfilling all AN criteria. RESULTS: Patients receiving CBT-E reported more on "applying therapy" in the initial and the final treatment phase compared to FPT patients. In terms of process-outcome relations, higher levels of "recreating the therapeutic dialogue between sessions," "recreating the therapeutic dialogue with negative emotions" as well as "applying therapy with negative emotions" in the final phase of treatment predicted negative outcome in FPT, whereas overall higher levels of negative emotions predicted negative outcome in CBT-E. CONCLUSIONS: In outpatient treatment in AN, the processing of therapy as measured by the IEQ showed surprisingly few differences between CBT-E and FPT. However, different ISP patterns were predictive of outcome, pointing to different mechanisms of change.

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting.

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

Severity of bulimia nervosa. Measurement and classification into health or pathology.

AIMS: In order to identify the most important components of the severity of bulimia nervosa (as well as identifying clinical cases), we explored the relation between dimensional and categorical assessment. This was achieved by studying the performance of variables from standard instruments (measuring specific and general psychopathology) in predicting an expert rating of overall syndrome severity. METHOD: In total, 213 cases were selected (across the whole range of severity). We applied regression with optimal scaling to model nonlinear relations in the data, and the lasso method with bootstrapping for predictor selection. The best model contained 2 scales of the Eating Disorders Inventory ('bulimia' and 'drive for thinness') and the frequency of the binges. The sensitivity and specificity of case classification using the obtained model was determined. RESULTS: The model can predict the probability of being a clinical case at a rate of 88%. The presented statistical methods are innovative and promising approaches that can help researchers and clinicians to better define sets of variables for treatment evaluation and outcome studies. CONCLUSION: The results indicate that severity and outcome in bulimia nervosa should be determined by measuring both cognitive and behavioral aspects of the symptoms.

Symptom severity and treatment course of bulimic patients with and without a borderline personality disorder.

There are contradictory results concerning the frequency of borderline personality disorder (BPD) in bulimic patients and its impact on eating pathology and treatment outcome. We evaluated 240 patients with bulimia nervosa using EDI-2, SIAB and SCL-90-R. Only a minority of patients had a BPD (13.8%). There were no differences in binging or purging behaviour between patients with and without BPD, but borderline patients had significantly more feelings of ineffectiveness and more disturbances in interoceptive awareness. Bulimic patients with BPD showed significantly more general psychopathology. Although, BPD patients started with higher levels of pathology, there were similar reductions of symptoms over the course of treatment in both groups. Psychotherapy in bulimic patients with a BPD has to focus not only on eating pathology but also on aspects that are caused by the severe personality disturbance.

[Bulimia nervosa]. / Bulimia nervosa.

Bulimia nervosa is characterized by episodes of binge eating and compensatory behaviours (self-induced vomiting, laxative misuse, dietary restriction). It has a complex aetiology and is mostly found in young women. Bulimia leads to substantial physical and psychosocial morbidity. Bulimia nervosa needs specialized psychotherapeutic treatment. In most cases outpatient treatment is sufficient, but comorbidity with other psychiatric disturbances has to be taken into account. Additional psychopharmacological interventions might be helpful. After 5 to 10 years about 50% of the patients show complete remissions, 30% partial remissions and about 20% a chronic course of the illness. General practitioners, dentists and gynaecologists should be informed about typical signs of the disorder that is often hidden by the patients.

[Cytotoxic compounds from the marine actinobacterium].

We isolated a bioactive streptomycete from marine sediment samples collected at Bay of Bengal, India, during our systematic study of marine actinobacteria. The taxonomic studies indicated that the isolate is related to Strepomyces corchorusii. However, it differed in certain aspects, and, hence, was designated as S. corchorusii AUBN(1)/7. A solvent extraction followed by a chromatographic purification helped obtain from the isolate two cytotoxic compounds, which were identified as resistomycin, a quinone-related antibiotic, and tetracenomycin D, an anthraquinone antibiotic, on the basis of spectral data of pure compounds. They demonstrated in vitro a potent cytotoxic activity against cell lines HMO2 (gastric adenocarcinoma) and HepG2 (hepatic carcinoma) and also exhibited weak antibacterial activities against Gram-positive and Gram-negative bacteria. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas sp.: Production and structure elucidation.

The new marine Halomonas sp. strain GWS-BW-H8hM (DSM 17996) was found to produce 3-(4'-hydroxyphenyl)-4-phenylpyrrole-2,5-dicarboxylic acid (HPPD-1) and 3,4-bis(4'-hydroxy- phenyl)pyrrole-2,5-dicarboxylic acid (HPPD-2). In initial cultivations using marine broth, only low contents of these compounds have been isolated. Improving the conditions and growing the strain on artificial seawater supplemented with tryptone 10 g l(-1), yeast extract 5 g l(-1), L-tyrosine 0.6 g l(-1), glycine 1 g l(-1), and glucose 6 g l(-1), the growth-associated HPPD-1 and HPPD-2 production of a 40-l batch cultivation reached the amounts of 47 mg l(-1) and 116 mg l(-1), respectively, after 65 h. Both compounds showed potent anti-tumor-promoting activities.

Drop outs from in-patient treatment of anorexia nervosa.

OBJECTIVE: Aim of the study was to identify patient characteristics that distinguish drop outs and completers from in-patient treatment for anorexia nervosa. METHOD: A total of 133 consecutively admitted in-patients with anorexia nervosa (age range 16-50 years; 92.5% women) were analysed using sociodemographic variables as well as measures of psychopathology (SCL-90-R, EDI-2) and interpersonal difficulties (IIP-C). Patients were treated in a multimodal treatment setting, combining cognitive-behavioural and psychodynamic components. RESULTS: Patients, who reported fewer symptoms, were hospitalized before and had a comorbid depression stayed more often in psychotherapy. Patients dropping out of treatment (31.6%) showed a trend to higher levels of maturity fears. Subtype, age, duration of illness, comorbid personality disorders or previous drop outs were not predictive of dropping out. CONCLUSION: Addressing the high ambivalence and maturity fears of anorexic patients should be an essential issue in psychotherapy with this patient group.

[Psychosomatic liaison service in neurology. Accordance between need for psychotherapeutic interventions and their realization]. / Psychosomatischer Liaisondienst in der Neurologie. Zusammenhänge zwischen Behandlungsbedarf und Realisierung psychotherapeutischer Interventionen.

The study addresses the realization of psychotherapeutic interventions in the framework of an integrated psychosomatic liaison service in neurology. Eighty-four patients from one unit at the Department of Neurology of the University of Freiburg, Germany, underwent structured psychodiagnostic interviews and filled in self-rating instruments to evaluate mental disorders, psychosocial distress, ways of coping, and quality of life. Motivation and the need for treatment were estimated by both patients and a liaison psychotherapist. Using ICD-10-F criteria, mental and behavioral disorders were diagnosed in 35% of the cases. Thirty-seven percent of the patients desired psychological support. Actual intervention occurred in 27%, with a mean consultation rate of 3.7 sessions. There was only slight agreement between the estimated need for treatment and the interventions actually performed. The realization of psychotherapeutic interventions was subject to a complex interaction between patient needs, "objective" psychosocial distress, and institutional factors. Differentiation between primary medical care and psychotherapy was difficult.

Need and use of psychotherapeutic interventions within a psychosomatic liaison service in neurology.

OBJECTIVES: The study addresses the evaluation of psychosocial distress, the need for care as determined by a psychotherapist and patients, and the realization of psychotherapeutic interventions within a routine psychosomatic liaison service. MATERIAL AND METHODS: A total of 84 patients from one unit at the Department of Neurology of the University of Freiburg, Germany, underwent a structured psychodiagnostic interview and filled out self-rating instruments to evaluate mental disorders, psychosocial distress, ways of coping strategies and quality of life. The need for treatment and the motivation of patients were estimated by both patients and a liaison psychotherapist. RESULTS: Using ICD-10-F criteria, mental and behavioral disorders were diagnosed in 35% of cases. Professional assessment indicated a need for psychotherapeutic treatment in 37% of patients; actual intervention occurred in 27%. Only slight agreement was found between the estimated need for treatment and the interventions actually performed. CONCLUSIONS: The realization of psychotherapeutic interventions is subject to a complex interaction between the needs of a patient, the "objective" psychosocial distress of the patient, and institutional factors. About 10% of the hospitalized patients considered in the study need continuous psychotherapeutic treatment.

The structures of antioxidant and cytotoxic agents from natural source: anthraquinones and tannins from roots of Rumex patientia.

A new anthraquinone glycoside, emodin-6-O-beta-D-glucopyranoside, and a new simple halogenated flavan-3-ol, 6-chlorocatechin, have been isolated from the roots of Rumex patientia L. together with seven known phenolic compounds. Their structures were elucidated on the basis of spectroscopic methods. Cytotoxic effects and radical scavenging properties of the isolated compounds have been demonstrated.

Bagremycin A and B, novel antibiotics from streptomyces sp. Tü 4128.

Two novel secondary metabolites, bagremycin A (2) and B (3), were detected in the culture filtrate of Streptomyces sp. Tü 4128 by HPLC-diode-array screening. They are phenol esters of 3-amino-4-hydroxybenzoic acid with a derivative of p-coumaric acid and show a moderate activity against gram-positive bacteria and some fungi.

Two new chlorinated naphthalene glycosides from Rumex patientia.

Two new naphthalene derivatives, named patientosides A (1) and B (2), were isolated from the roots of Rumex patientia. The structures of the new compounds were established as 2-acetyl-4-chloro-1,8-dihydroxy-3-methylnaphthalene-8-O-beta-D-glucopyranoside (1) and 2,4-dichloro-1,8-dihydroxy-3-methylnaphthalene-8-O-beta-D-glucopyranoside (2) by means of spectroscopic methods.

Five naphthalene glycosides from the roots of Rumex patientia.

Three novel and two known naphthalene glycosides were isolated from the roots of Rumex patientia L. (Polygonaceae). The structures of the new compounds were established, respectively as 2-acetyl-3-methyl-6-carboxy-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranoside, 4,4"-binaphthalene-8,8"-O,O-di-beta-D-glucopyranoside and 2-acetyl-3-methyl-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranosyl (1-->3) beta-D-glucopyranoside on the basis of spectral analysis. The other napthalene glycosides were determined as nepodin-8-O-beta-D-glucopyranoside and torachrysone-8-O-beta-D-glucopyranoside by comparison of their spectral data with those previously reported.

Enterobactin: the characteristic catecholate siderophore of Enterobacteriaceae is produced by Streptomyces species.(1).

Enterobactin is described in the literature as the typical iron-chelating compound (siderophore) produced by bacteria of the family Enterobacteriaceae. In the course of a HPLC with diode array detection screening programme for detection of novel secondary metabolites, enterobactin, its biosynthetic precursor 2,3-dihydroxy-N-benzoylserine and its linear dimer and trimer condensation products were found to be produced by two Streptomyces strains besides the trihydroxamate-type siderophores desferri-ferrioxamine B and E.

Semisynthetic derivatives of concanamycin A and C, as inhibitors of V- and P-type ATPases: structure-activity investigations and developments of photoaffinity probes.

V-type ATPases are inhibited by the plecomacrolides bafilomycin and concanamycin, which exert their inhibitory potential at nanomolar concentrations. In addition, some P-type ATPases are inhibited at micromolar concentrations. We initiated intensive structure-activity investigations with semisynthetic concanamycin derivatives to approach the following two questions: (i) What is the pharmacophor, the structural key element, of the plecomacrolides that leads to their inhibitory potential against V- and P-type ATPases? (ii) Where is the binding site within these two different types of ATPases? In a first step, we examined where chemical modifications (O-acylations, substitutions, eliminations) could be placed without seriously affecting the inhibitory potential of the macrolides. In a second step, we used the knowledge of these structure-activity investigations to introduce traceable elements (fluorescent or radioactive) or nitrene-generating azido or carbene-generating diazirine-groups able to bind the inhibitors to their target covalently. These studies led finally to the synthesis of two photoaffinity probes that were used in labeling experiments with the purified plasma membrane V-type ATPase of Manduca sexta (described in a following paper, Huss, M., Gassel, M., Ingenhorst, G., Dröse, S., Zeeck, A., Altendorf, K., Wieczorek, H., manuscript submitted).

New co-metabolites of the streptazolin pathway.

Variation of the culture conditions of Streptomyces sp. strain A1, which produces streptazolin (1), resulted in the isolation of four new co-metabolites: 5-O-(beta-D-xylopyranosyl)streptazolin (3), 9-hydroxystreptazolin (4), 13-hydroxystreptazolin (5), and streptenol E (6). Their structures were established by spectroscopic and chemical methods. The possible biosynthetic relationship between the streptazolins and the streptenols is discussed.