Brain-derived neurotrophic factor (BDNF) gene : no major impact on antidepressant treatment response

The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p=0.01) particularly in anxious depression (p=0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TT

The cost effectiveness of Naltrexone added to cognitive-behavioral therapy in the treatment of alcohol dependence

he purpose of this study was to evaluate the comparative cost of treating alcohol dependence with either cognitive behavioral therapy (CBT) alone or CBT combined with naltrexone (CBT+naltrexone). Two hundred ninety-eight outpatients dependent on alcohol who were consecutively treated for alcohol dependence participated in this study. One hundred seven (36%) patients received adjunctive pharmacotherapy (CBT+naltrexone). The Drug Abuse Treatment Cost Analysis Program was used to estimate treatment costs. Adjunctive pharmacotherapy (CBT+naltrexone) introduced an additional treatment cost and was 54% more expensive than CBT alone. When treatment abstinence rates (36.1% CBT; 62.6% CBT+naltrexone) were applied to cost effectiveness ratios, CBT+naltrexone demonstrated an advantage over CBT alone. There were no differences between groups on a preference-based health measure (SF-6D). In this treatment center, to achieve 100 abstainers over a 12-week program, 280 patients require CBT compared with 160 CBT+naltrexone. The dominant choice was CBT+naltrexone based on modest economic advantages and significant efficiencies in the numbers needed to treat.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication

This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

Kava and St. John's wort : current evidence for use in mood and anxiety disorders

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St John’s wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. Objectives: To conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in Major Depressive Disorder (MDD), Bipolar Disorder (BP), Seasonal Affective Disorder (SAD), Generalized Anxiety Disorder (GAD), Social Phobia (SP), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), and Post Traumatic Stress Disorder (PTSD). Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St John’s wort, Hypericum perforatum, hypericin and hyperforin. Additional search criteria for safety, pharmacodynamics , and pharmacokinetics was employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD or SP. These disorders constitute potential applications that warrant exploration. Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

A research opportunity : “3D-ROSE” : virtual reality preparation for children having radiotherapy or imaging procedures

Professor Christian Langton is a medical physicist at Queensland University of Technology in Brisbane. He has developed a way of preparing children who are about to have either radiotherapy or MRI imaging procedures and is seeking research partners to develop and test these further. This is a great opportunity for nurses interested in research, and who have access to a children’s hospital, to work with Professor Langton on some truly innovative, multidisciplinary research.

Narrative therapy for adults with major depressive disorder: Improved symptom and interpersonal outcomes

Abstract This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder. RÉSUMÉ Cette étude a investigué les symptômes dépressifs et les relations interpersonnels d'une thérapie narrative en huit séances chez 47 adultes souffrant d'un trouble dépressif majeur. Après la thérapie, l'amélioration des symptômes dépressifs (d=1.36) et la proportion de clients atteignant un changement significatif (74%), le mouvement vers la population fonctionnelle (61%), enfin l'amélioration clinique significative (53%) étaient comparables aux performances des études de résultats. L'amélioration des relations interpersonnelles (d=0.62) était inférieure à l'amélioration symptomatique. Le suivi à trois mois montrait un maintien des gains symptomatiques mais pas pour les relations interpersonnelles. L’évaluation des performances et les analyses de significativité clinique modèrent les limitations du plan de recherche à mesures répétées et apportent une preuve empirique qui étaie l'efficacité des thérapies narratives pour des adultes avec un trouble dépressif majeur. Este estudo investigou sintomas depressivos e resultados interpessoais relacionados em oito sessões de terapia narrativa manualizada para 47 adultos com perturbação depressiva major. No pós terapia, melhoria de sintomas depressivos (d=1,36) e proporção de clientes que alcançam melhoria válida (74%), movimento para a população funcional (61%) e melhoria clinicamente significativa (53%) foram comparáveis com os resultados da investigação reportados. As melhorias pós terapia nos resultados interpessoais relacionados (d=.62) foi menos substancial do que para os sintomas. Aos três meses de seguimento houve a manutenção dos sintomas mas não dos ganhos interpessoais. As análises de benchemarking e de melhoria clinicamente significativas atenuam as limitações de um design de medidas repetidas, fornecendo evidência empírica para a terapia narrativa para adultos com perturbação depressiva major. Questo lavoro ha valutato i sintomi depressivi e gli outcome nella capacità di relazionarsi a livello interpersonale in 8 sedute di psicoterapia narrativa manualizzata in un gruppo di 47 adulti con depressione maggiore. I risultati ottenuti relativamente a: post terapy, miglioramento dei sintomi depressivi (d_1.36), proporzione di pazienti che hanno raggiunto un miglioramento affidabile e consistente (74%), movimento verso il funzionamento atteso nella popolazione (61%) e miglioramento clinicamente significativo (53%) sono paragonabili ai valori di riferimento della ricerca sull'outcome. I miglioramento della capacità di relazionarsi valutata alla fine del trattamento (d_.62) si è rivelata meno sostanziale rispetto ai sintomi. Un follow-up dopo 3 mesi ha dimostrato che il miglioramento sintomatologico è stato mantenuto, ma non quello degli obiettivi interpersonali. Valori di riferimento e analisi della significatività clinica hanno fatto fronte ai limiti del disegno a misure ripetute, offrendo prove empiriche sulla rilevanza della terapia narrativa in pazienti adulti con depressione maggiore

Schizophrenia and the progression of emotional expression in relation to others

Gaining an improved understanding of people diagnosed with schizophrenia has the potential to influence priorities for therapy. Psychosis is commonly understood through the perspective of the medical model. However, the experience of social context surrounding psychosis is not well understood. In this research project we used a phenomenological methodology with a longitudinal design to interview 7 participants across a 12-month period to understand the social experiences surrounding psychosis. Eleven themes were explicated and divided into two phases of the illness experience: (a) transition into emotional shutdown included the experiences of not being acknowledged, relational confusion, not being expressive, detachment, reliving the past, and having no sense of direction; and (b) recovery from emotional shutdown included the experiences of being acknowledged, expression, resolution, independence, and a sense of direction. The experiential themes provide clinicians with new insights to better assess vulnerability, and have the potential to inform goals for therapy.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Neuronal nicotinic acetylcholine receptors : neuroplastic changes underlying alcohol and nicotine addictions

Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.

Varenicline decreases alcohol consumption in heavy-drinking smokers

Rationale Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR α4β2 subunit partial agonist varenicline (Chantix™), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518–12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655–663, 2011; McKee et al., Biol Psychiatry 66:185–190 2009). Objectives We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n = 64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens. Results Varenicline significantly decreases alcohol consumption (χ 2 = 35.32, p < 0.0001) in smokers. Although varenicline has previously been associated with suicidality and depression, side effects were low in this study and declined over time in the varenicline treatment group. Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.

Validating a screening tool for mental health and substance use risk in an Indigenous prison population

Introduction and Aims: The Indigenous Risk Impact Screen (IRIS) is a validated culturally appropriate and widely used tool in the community for assessing substance use and mental disorder. This research aimed to assess the utility of this tool in an Indigenous prison population. Design and Methods: The study used data collected from a cross-sectional study of mental health among indigenous inmates in Queensland custodial centres (n=395, 84% male). Participants were administered a modified version of the IRIS, and ICD-10 diagnoses of substance use, depressive and anxiety disorders obtained using the Composite International Diagnostic Interview (CIDI). The concurrent validity of the modified IRIS was assessed against those of the CIDI. Results: 312 people screened as high risk for a substance use disorder and 179 were high risk for mental problems. 73% of males and 88% of females were diagnosed with a mental disorder. The IRIS was an effective screener for substance use disorders, with high sensitivity (Se) of 94% and low specificity (Sp) of 33%. The screener was less effective in identifying depression (Se 82%, Sp 59%) and anxiety (Se 68%, Sp 60%). Discussion: The IRIS is the first culturally appropriate screening instrument to be validated for the risk of drug and alcohol and mental disorder among Indigenous adults in custody. Conclusions: This study demonstrated that the IRIS is a valid tool for screening of alcohol and drug use risk among an incarcerated Indigenous population. The IRIS could offer an opportunity to improve the identification, treatment and health outcomes for incarcerated Indigenous adults.

Cognitive remediation : the foundation of psychosocial treatment of schizophrenia

Despite advances in psychopharmacology, schizophrenia remains a severely disabling illness. It is now appreciated that cognitive impairment mediates the functional disability associated with the disorder. Cognitive remediation which is defined as “a behavioural training based intervention that aims to improve cognitive processes (attention, memory, executive functioning, social cognition or meta cognition) with the goal of durability and generalization” is a therapeutic approach that improves cognition and when combined with other rehabilitation strategies improves real world functioning (Wykes et al., 2011).