Adapting CBT to treat depression in Armed Forces Veterans: qualitative study.

BACKGROUND: The principles of the Armed Forces Covenant state that Armed Forces Veterans should be at no disadvantage resulting from their service compared with a general adult population. However, despite being at increased risk of experiencing common mental health difficulties, evidence indicates that 82% of Armed Forces Veterans receive no treatment, compared with 63% of the general adult population. AIM: To gain a better appreciation of factors that inform the type of adaptations to cognitive behavioural therapy (CBT) interventions for depression and mainstream service promotion materials to enhance acceptability for Armed Forces Veterans. METHOD: This is a qualitative study employing a focus group of 12 participants to examine the main impacts of depression on Armed Forces Veterans alongside attitudes towards terminology and visual imagery. Thematic analysis was used to identify themes and sub-themes with rigour established through two researchers independently developing thematic maps to inform a final agreed thematic map. RESULTS: A behavioural activation intervention supporting re-engagement with activities to overcome depression had good levels of acceptability when adapted to reflect an Armed Forces culture. Preferences regarding terminology commonly used within CBT adapted for Armed Forces Veterans were identified. Concerns were expressed with respect to using imagery that emphasized physical rather than mental health difficulties. CONCLUSIONS: There is the need to consider the Armed Forces community as a specific institutional culture when developing CBT approaches with potential to enhance engagement, completion and recovery rates. Results have potential to inform the practice of CBT with Armed Forces Veterans and future research.

Psychological distress (depression and anxiety) in people with head and neck cancers.

OBJECTIVE: To assess symptoms of depression and anxiety in patients with head and neck cancers (HNCs) before and after radiotherapy. DESIGN, PARTICIPANTS AND SETTING: Prospective observational study of 102 outpatients with HNCs at a tertiary cancer centre in Melbourne between 1 May 2008 and 30 May 2009. Eligibility criteria were a first-time diagnosis of HNC, age over 17 years, and agreement to undergo cancer treatment involving radiotherapy with curative intent. Data were collected before commencement of radiotherapy and again 3 weeks after completing treatment. MAIN OUTCOME MEASURES: Symptoms of depression and anxiety as assessed by the Hospital Anxiety and Depression Scale (HADS); physical and psychosocial aspects of quality of life as assessed by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). RESULTS: Seventy-five participants completed pretreatment and posttreatment questionnaires. Mean depression scores increased significantly from before to after treatment, while anxiety scores decreased significantly over the same period. The prevalence of mild to severe depression was 15% before treatment and 31% after treatment. The prevalence of mild to severe symptoms of anxiety was 30% before treatment, reducing to 17% after treatment. Posttreatment depression was predicted by pretreatment depression and receiving chemotherapy. Posttreatment anxiety was predicted by pretreatment anxiety and male sex. CONCLUSIONS: These findings suggest that rates of depression in patients with HNCs increase after cancer treatment, with a third of patients experiencing clinically significant symptoms of depression after radiotherapy.

Exocytosis of CTLA-4 is dependent on phospholipase D and ADP ribosylation factor-1 and stimulated during activation of regulatory T cells.

CTLA-4 is an essential protein in the regulation of T cell responses that interacts with two ligands found on the surface of APCs (CD80 and CD86). CTLA-4 is itself poorly expressed on the T cell surface and is predominantly localized to intracellular compartments. We have studied the mechanisms involved in the delivery of CTLA-4 to the cell surface using a model Chinese hamster ovary cell system and compared this with activated and regulatory human T cells. We have shown that expression of CTLA-4 at the plasma membrane (PM) is controlled by exocytosis of CTLA-4-containing vesicles and followed by rapid endocytosis. Using selective inhibitors and dominant negative mutants, we have shown that exocytosis of CTLA-4 is dependent on the activity of the GTPase ADP ribosylation factor-1 and on phospholipase D activity. CTLA-4 was identified in a perinuclear compartment overlapping with the cis-Golgi marker GM-130 but did not colocalize strongly with lysosomal markers such as CD63 and lysosome-associated membrane protein. In regulatory T cells, activation of phospholipase D was sufficient to trigger release of CTLA-4 to the PM but did not inhibit endocytosis. Taken together, these data suggest that CTLA-4 may be stored in a specialized compartment in regulatory T cells that can be triggered rapidly for deployment to the PM in a phospholipase D- and ADP ribosylation factor-1-dependent manner.

CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells.

Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we investigated the ability of their two natural ligands, CD80 and CD86, to influence the Treg-suppressive capacity. During T cell responses to alloantigens expressed on dendritic cells, we observed that Abs against CD86 potently enhanced suppression by CD4(+)CD25(+) Treg. In contrast, blocking CD80 enhanced proliferative responses by impairing Treg suppression. Intriguingly, the relative expression levels of CD80 and CD86 on dendritic cells are modulated during progression from an immature to a mature state, and this correlates with the ability of Treg to suppress responses. Our data show that CD80 and CD86 have opposing functions through CD28 and CTLA-4 on Treg, an observation that has significant implications for manipulation of immune responses and tolerance in vivo.

Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T cells.

CD28 and CTLA-4 are opposing regulators of T cell activation, triggered by the two ligands CD80 and CD86. How these ligands promote either T cell activation via CD28 or inhibition via CTLA-4 is not understood. Using CD80 and CD86 molecules expressed on transfected cells, we have identified a major difference between these ligands in that CD80 transfectants have the ability to inhibit activation of resting human peripheral blood T cells via interaction with CTLA-4, whereas CD86 transfectants do not. Rather, CTLA-4-CD86 interactions appear to contribute towards T cell proliferation. We also observed that CTLA-4 function is strongly influenced by TCR stimulation, effects being observed only at relatively low levels of TCR stimulation. The kinetics of CD80-CTLA-4 interactions revealed that CTLA-4 inhibition took place within the first 8 h of T cell stimulation, despite there being little measurable CTLA-4 expression on the majority T cells. However, significant amounts of CTLA-4 were observed in the CD25(+) CD4(+) subset of T cells which, when removed from the cultures, accounted for the CTLA-4 inhibition observed. Overall, these data provide evidence that CD80 and CD86 differ in their interactions with CTLA-4 and that CD80 appears to be the preferential inhibitory ligand for CTLA-4 working via a population of CD4(+) CD25(+) CTLA-4(+) regulatory T cells.

Discontinuation of Antipsychotics in Nursing Home Patients With Dementia.

The authors assessed the consequences of stopping antipsychotic medication in nursing home patients with dementia, as mandated by federal regulations (OBRA 87). They studied three patient groups: 1) a group ("clinical judgment") whose antipsychotics were discontinued at the discretion of their physicians; 2) a group ("empirical") with mandated cessation of antipsychotics in the facility; and 3) a comparison group of patients not receiving medication. The primary outcome measure was the necessity to resume antipsychotic or other psychotropic medication ("failure"). Also, assessments of behavior, function, neurologic status, and cognition were performed by blind raters. The failure rate in the empirical withdrawal group was 50%, 10 times that of the clinical judgment group. Among failures, the most striking result was increased verbal and physical aggression. No failures occurred in the comparison group. There were no benefits of antipsychotic withdrawal in terms of neurological performance, functional status, or cognition.