Maintenance cognitive-behavioral therapy and manualized psychoeducation in the treatment of recurrent depression: a multicenter prospective randomized controlled trial.

OBJECTIVE: This multicenter study compared the relapse and recurrence outcomes of two active treatments, maintenance cognitive-behavioral therapy (CBT) and manualized psychoeducation, both in addition to treatment as usual, in patients in remission from depression. METHOD: This was a multicenter prospective randomized observer-blinded study with two parallel groups. The authors assessed 180 patients with three or more previous major depressive episodes who met remission criteria over a 2-month baseline period and who were randomly assigned to 16 sessions of either maintenance CBT or manualized psychoeducation over 8 months and then followed up for 12 months. The main outcome measure was time to first relapse or recurrence of a major depression, based on DSM-IV criteria, as assessed by blinded observers with the Longitudinal Interval Follow-Up Evaluation. RESULTS: Cox regression analysis showed that time to relapse or recurrence of major depression did not differ significantly between treatment conditions, but a significant interaction was observed between treatment condition and number of previous episodes (<5 or ≥5). Within the subsample of patients with five or more previous episodes, maintenance CBT was significantly superior to manualized psychoeducation, whereas for patients with fewer than five previous episodes, no significant treatment differences were observed in time to relapse or recurrence. CONCLUSIONS: The results indicate that maintenance CBT has significant effects on the prevention of relapse or recurrence only in patients with a high risk of depression recurrence. For patients with a moderate risk of recurrence, nonspecific effects and structured patient education may be equally effective.

The influence of Antonovsky's sense of coherence (SOC) and psychoeducational family intervention (PEFI) on schizophrenic outpatients' perceived quality of life: a longitudinal field study.

BACKGROUND: Antonovsky's sense of coherence (SOC) as well as psychoeducational interventions has a convincing impact on the quality of life (QOL) of patients suffering from schizophrenia. This study explores the influence of SOC on QOL among participants of a PEFI group (PG) compared to a control group (CG). METHODS: In a quasi-experimental field study 46 schizophrenic outpatients had an option to participate together with their family members the PG (n = 25) or the CG (n = 21). They were assessed amongst others with the Quality of Life Questionnaire (WHOQOL-BREF), the Global Assessment of Functioning Scale (GAF), the Positive and Negative Syndrome Scale (PANSS) and the Sense of Coherence Scale (SOC-29). The efficacy of the PG on QOL was compared to the CG within two different SOC levels. RESULTS: Before intervention patients with high SOC scores had significant higher levels in GAF and QOL and a trend of lower PANSS scores. The strongest relationship was found between SOC and QOL. Regarding the SOC level after intervention PG participants had higher QOL values than the CG within the last three measurements. The highest benefit due to QOL was observed within PG participants with high SOC scores. CONCLUSIONS: The results of the study suggest that SOC is a good predictive variable for clinical outcomes including QOL. Generally, the influence of the SOC level on QOL was stronger than the effect of PEFI. Hence schizophrenic patients with high SOC scores did benefit most from participating in a PG regarding their QOL. To optimize the effect of PEFI more efforts are needed to enhance the SOC of the participants. Altogether PEFI seems to be an important completion to the standard treatment for schizophrenic outpatients.

Photoaffinity cross-linking of the corticotropin-releasing factor receptor type 1 with photoreactive urocortin analogues.

Interaction of natural peptide ligands with class 2 GPCRs, which are targets of biologically important hormones such as glucagon, secretin, and corticotropin-releasing factor (CRF), occurs with a common orientation, in that the ligand C-terminus binds to the extracellular receptor N-terminus, whereas the ligand N-terminus binds to the receptor juxtamembrane domain. N-Terminal truncation, by eight amino acids in the case of CRF, leads to antagonists, suggesting those residues constitute the receptor activating sequence. Here, we identified by photoaffinity cross-linking using p-benzoyl-l-phenylalanine (Bpa) analogues of urocortin (Ucn) the most affine CRF receptor agonist, interaction domains of CRF(1) receptor with Bpa residues at exclusive positions. Specific cleavage patterns of the corresponding ligand-receptor complexes, obtained using several cleavage methods in combination with SDS-PAGE for fragment size determination, showed that a Bpa group located N-terminally or in position 12 binds at the second and such in position 17 or 22 at the first extracellular receptor loop. Our results indicate that the very N-terminal ligand residues (1-11), which are responsible for receptor activation, are oriented to the juxtamembrane domain by interaction of amino acid residues 12, 17, and 22. Our findings contradict a recently proposed interaction model derived from ligand interaction with a soluble receptor N-terminus, indicating that conclusions drawn from such a reduced system may be of limited value to understand the interaction with the full-length receptor.

Enhancement of intracellular concentration and biological activity of PNA after conjugation with a cell-penetrating synthetic model peptide.

In order to evaluate the ability of the cell-penetrating alpha-helical amphipathic model peptide KLALKLALKALKAALKLA-NH(2) (MAP) to deliver peptide nucleic acids (PNAs) into mammalian cells, MAP was covalently linked to the 12-mer PNA 5'-GGAGCAGGAAAG-3' directed against the mRNA of the nociceptin/orphanin FQ receptor. The cellular uptake of both the naked PNA and its MAP-conjugate was studied by means of capillary electrophoresis combined with laser-induced fluorescence detection, confocal laser scanning microscopy and fluorescence-activated cell sorting. Incubation with the fluorescein-labelled PNA-peptide conjugate led to three- and eightfold higher intracellular concentrations in neonatal rat cardiomyocytes and CHO cells, respectively, than found after exposure of the cells to the naked PNA. Correspondingly, pretreatment of spontaneously-beating neonatal rat cardiomyocytes with the PNA-peptide conjugate and the naked PNA slowed down the positive chronotropic effect elicited by the neuropeptide nociceptin by 10- and twofold, respectively. The main reasons for the higher bioavailability of the PNA-peptide conjugate were found to be a more rapid cellular uptake in combination with a lowered re-export and resistance against influences of serum.

Regulation of the coupling to different G proteins of rat corticotropin-releasing factor receptor type 1 in human embryonic kidney 293 cells.

The regulation of G protein activation by the rat corticotropin-releasing factor receptor type 1 (rCRFR1) in human embryonic kidney (HEK)293 (HEK-rCRFR1) cell membranes was studied. Corresponding to a high and low affinity ligand binding site, sauvagine and other peptidic CRFR1 ligands evoked high and low potency responses of G protein activation, differing by 64-fold in their EC(50) values as measured by stimulation of [(35)S]GTPgammaS binding. Contrary to the low potency response, the high potency response was of lower GTPgammaS affinity, pertussis toxin (PTX)-insensitive, and homologously desensitized. Distinct desensitization was also observed in the adenylate cyclase activity, when its high potency stimulation was abolished and the activity became low potently inhibited by sauvagine. From these results and immunoprecipitation of [(35)S]GTPgammaS-bound Galpha(s) and Galpha(i) subunits it is concluded that the high and low potency [(35)S]GTPgammaS binding stimulation reflected coupling to G(s) and G(i) proteins, respectively, only G(s) coupling being homologously desensitized. Immunoprecipitation of [(35)S]GTPgammaS-bound Galpha(q/11) revealed additional coupling to G(q/11), which also was homologously desensitized. Although Galpha(q/11) coupling was PTX-insensitive, half of the sauvagine-stimulated accumulation of inositol phosphates in the cells was PTX-sensitive, suggesting involvement of G(i) in addition to G(q/11)in the stimulation of inositol metabolism. It is concluded that CRFR1 signals through at least two different ways, one leading to G(s)- and G(q/11)-mediated signaling steps and desensitization and another leading to G(i) -mediated signals without being desensitized. Furthermore, the concentrations of the stimulating ligand and GTP and desensitization may be part of a regulatory mechanism determining the actual ratio of the coupling of CRFR1 to different G proteins.

[Medication in acute psychiatric treatment]. / Die Akutbehandlung mit Psychopharmaka in den Jahren 1990 - 2000 - Ergebnisse einer Umfrage zu den Verordnungsgewohnheiten psychiatrischer Kliniken.

The aim of the study - undertaken at eight psychiatric hospitals in Hessen - was to analyse the practice in psychopharmacological treatment of schizophrenia and suicidal tendencies. The results indicate that inpatient antipsychotic treatment practice significantly differs from current therapeutic guidelines. Atypical neuroleptic medication is prescribed to a much lesser extent than would have been expected, especially regarding the official therapeutic guidelines. The inpatient treatment practice of acute suicide in severe depression, on the other hand, is concomitant with the therapeutic guidelines. The results are discussed and the development of guidelines for inpatient routine - oriented towards the current guidelines for psychopharmaceutical treatment - is suggested.

[Health promotion--a new approach in psychiatry]. / Gesundheitsförderung--Ein neuer Weg in der Psychiatrie.

Since its beginnings, the ideology of psychiatry has been determined by the paradigm of a disease model. Practically all psychiatric schools are characterized by their orientation towards a morbid, atypical behaviour. This, however, inevitably narrows the view of the soul of a person. Despite mental illness, resources are always present, these though are not recognized and not utilized. The theory of salutogenesis with its search for health preserving factors has significantly expanded insight on dynamic mental processes. The resulting concept of health promotion attempts to develop patient's self-healing powers by identifying healthy parts and supporting them by instructing patients in active participation. From a health promotion viewpoint, it is necessary to intervene at three levels: 1. At the patient level in the form of guidance and help to actively participate in the healing process. 2. At the staff level in the form of creating healthy work conditions and the promotion of active participation in the creation of this work environment. 3. At the level of psychiatric institutions in the form of promoting efficient communications structures within and between the various services. This paper describes the concept of health promotion in psychiatric services and its possible influence on the reshaping of theory and practice in psychiatry--necessary in the face of current challenges.

Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)amide analogues. 1. In vitro studies.

Phe(4) in the nociceptin (NC) sequence has been identified as the most critical residue for receptor interaction. In the present study, we investigated the pharmacological activity of a series of NC(1-13)NH(2) analogues, in which the hydrogen atom in the para position of Phe(4) was substituted with F, NO(2), CN, Cl, Br, I, CH(3), OH or NH(2). In receptor binding studies, performed using CHO cells expressing the recombinant human NC receptor (CHO(hOP4)) and in rat cerebral cortex membranes, [(pF)Phe(4)]NC(1-13)NH(2), [(pNO(2))Phe(4)]NC(1-13)NH(2), and [(pCN)Phe(4)]NC(1-13)NH(2) displayed higher affinity than NC(1-13)NH(2). The affinity of [(pCl)Phe(4)]NC(1-13)NH(2) was essentially identical to that of NC(1-13)NH(2), while the remaining compounds displayed reduced affinity. In a series of functional assays (stimulation of GTPgammaS binding in CHO(hOP4)cells and rat cerebral cortex membranes and inhibition of cAMP accumulation in CHO(hOP4) cells), the para substituted analogues behaved as full agonists (with the exception of [(pOH)Phe(4)]NC(1-13)NH(2) which acted as a partial agonist in the GTPgammaS binding assays) with the following rank order potency:[(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2) were either inactive or displayed micromolar potencies in cAMP accumulation experiments performed on cells expressing classical opioid receptors. All compounds were full agonists in isolated tissues from various species (guinea pig ileum, mouse colon and mouse/rat vas deferens) with the exception of [(pOH)Phe(4)]NC(1-13)NH(2) which displayed partial agonist/weak antagonist activities. The rank order of potency was similar to that found in the other assays. The effects of all analogues were not modified by naloxone. The selective OP(4) receptor antagonist [Nphe(1)]NC(1-13)NH(2), tested in all preparations against one or both of the highly potent derivatives [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2), showed pA(2) values similar to those found against NC, the pA(2) in the GTPgammaS binding/rat cerebral cortex assay being much higher (ca. 7.5) than in the other functional assays (ca. 6). This study further supports the notion that Phe(4) of NC is the critical residue for receptor occupation and activation. Moreover, as part of this study, we have identified two novel, highly potent and selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2).