Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.     

Reduced serotonin-1A receptor binding in social anxiety disorder.

BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.     

Small bowel transplantation in the rat: impact of various immunosuppressive regimens on graft-versus-host reaction.

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.     

A pilot study of pulmonary rehabilitation in primary care.

Pulmonary rehabilitation is an effective intervention for patients with chronic obstructive pulmonary disease (COPD). It is usually available only through selected hospitals. A pilot study was undertaken to see if pulmonary rehabilitation performed by the primary health care team in one practice was feasible. Fourteen patients were recruited; 13 completed the programme and one year of follow-up. The programme was well received by patients and staff. There were not enough suitable patients among a practice list of 10,500 to justify the running of this programme for a single practice; one primary care group would suffice     

Self‐reflection and self‐practice in training of Cognitive Behaviour Therapy: an overview

The present paper deals with a developing training element in cognitive behaviour therapy (CBT), the self‐practice of therapeutic techniques and the self‐exploration of the person of the therapist. Initially, the current status of this training element in CBT is discussed, and a short note on its terminology is presented. Then an overview of the most important objectives of self‐practice and self‐reflection in CBT, and the concepts and methods of practice of this element is given. The concepts focus on two major aims, the self‐exploration of the person of the therapist within and beyond his or her therapeutic practice, and the self‐application of therapeutic techniques (= self‐practice). In the second part of the paper empirical studies related to the outcome of self‐reflection and self‐practice on the development of the therapist and her or his therapeutic practice are reviewed. The few empirical studies show that trainees experience in their own view substantial professional and personal gains from this training tool, with the professional impact being more important than the personal one. The most important outcomes evaluated by subjective data from the trainees are improvements in self‐insight and self‐awareness and a better understanding of the therapist's role and the therapeutic change process. Additionally, a better understanding of CBT methods and of general therapeutic skills, such as empathy and role‐taking‐competencies, are reported by the trainees. The paper comes to the conclusion that self‐exploration and self‐practice are important components of CBT training. Consequences and recommendations for its integration into training courses for CBT are discussed as well as the necessity for more research in this area. Copyright © 2002 John Wiley & Sons, Ltd.