Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD)

BACKGROUND PTSD is an anxiety disorder related to exposure to a severe psychological trauma. Symptoms include re-experiencing the event, avoidance and arousal as well as distress and impairment resulting from these symptoms.Guidelines suggest a combination of both psychological therapy and pharmacotherapy may enhance treatment response, especially in those with more severe PTSD or in those who have not responded to either intervention alone. OBJECTIVES To assess whether the combination of psychological therapy and pharmacotherapy provides a more efficacious treatment for PTSD than either of these interventions delivered separately. SEARCH STRATEGY Searches were conducted on the trial registers kept by the CCDAN group (CCDANCTR-Studies and CCDANCTR-References) to June 2010. The reference sections of included studies and several conference abstracts were also scanned. SELECTION CRITERIA Patients of any age or gender, with chronic or recent onset PTSD arising from any type of event relevant to the diagnostic criteria were included. A combination of any psychological therapy and pharmacotherapy was included and compared to wait list, placebo, standard treatment or either intervention alone. The primary outcome was change in total PTSD symptom severity. Other outcomes included changes in functioning, depression and anxiety symptoms, suicide attempts, substance use, withdrawal and cost. DATA COLLECTION AND ANALYSIS Two or three review authors independently selected trials, assessed their 'risk of bias' and extracted trial and outcome data. We used a fixed-effect model for meta-analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference and standardised mean difference were used to summarise continuous measures. MAIN RESULTS Four trials were eligible for inclusion, one of these trials (n =24) was on children and adolescents. All used an SSRI and prolonged exposure or a cognitive behavioural intervention. Two trials compared combination treatment with pharmacological treatment and two compared combination treatment with psychological treatment. Only two trials reported a total PTSD symptom score and these data could not be combined. There was no strong evidence to show if there were differences between the group receiving combined interventions compared to the group receiving psychological therapy (mean difference 2.44, 95% CI -2.87, 7.35 one study, n=65) or pharmacotherapy (mean difference -4.70, 95% CI -10.84 to 1.44; one study, n = 25). Trialists reported no significant differences between combination and single intervention groups in the other two studies. There were very little data reported for other outcomes, and in no case were significant differences reported. AUTHORS' CONCLUSIONS There is not enough evidence available to support or refute the effectiveness of combined psychological therapy and pharmacotherapy compared to either of these interventions alone. Further large randomised controlled trials are urgently required.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: A longitudinal MRI study

BACKGROUND: Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. AIMS: To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. METHOD: Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naive, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. RESULTS: There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naive and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. CONCLUSIONS: Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Pilot study evaluating the effect of massage therapy on stress, anxiety and aggression in a young adult psychiatric inpatient unit

Objective: The aim of the present pilot study was to examine the effectiveness of a relaxation massage therapy programme in reducing stress, anxiety and aggression on a young adult psychiatric inpatient unit. Method: This was a prospective, non-randomized intervention study comparing treatment as usual (TAU) with TAU plus massage therapy intervention (MT) over consecutive 7 week blocks (May–August 2006). MT consisted of a 20 min massage therapy session offered daily to patients during their period of hospitalization. The Kennedy Nurses’ Observational Scale for Inpatient Evaluation (NOSIE), the Symptom Checklist-90–Revised (SCL-90-R), the State–Trait Anxiety Inventory (STAI) and stress hormone (saliva cortisol) levels were used to measure patient outcomes at admission and discharge from the unit. The Staff Observation Aggression Scale–Revised (SOAS-R) was used to monitor the frequency and severity of aggressive incidents on the unit. Results: There was a significant reduction in self-reported anxiety (p < 0.001), resting heart rate (p < 0.05) and cortisol levels (p < 0.05) immediately following the initial and final massage therapy sessions. Significant improvements in hostility (p = 0.007) and depression scores (p < 0.001) on the SCL-90-R were observed in both treatment groups. There was no group×time interaction on any of the measures. Poor reliability of staff-reported incidents on the SOAS-R limited the validity of results in this domain. Conclusions: Massage therapy had immediate beneficial effects on anxiety-related measures and may be a useful de-escalating tool for reducing stress and anxiety in acutely hospitalized psychiatric patients. Study limitations preclude any definite conclusions on the effect of massage therapy on aggressive incidents in an acute psychiatric setting. Randomized controlled trials are warranted.

An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic-pituitary-adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n=20) and the total BPD cohort (n=20). However, within the BPD cohort, those exposed to childhood trauma (n=9) tended to have smaller pituitaries (-18%) than those with no history of childhood trauma (n=10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic-pituitary-adrenal axis dysfunction.

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis

Background We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. Methods Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. Results Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (−6%; p = .032). Conclusions The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Early maternal deprivation reduces prepulse inhibition and impairs spatial learning ability in adulthood: No further effect of post-pubertal chronic corticosterone treatment

Prolonged maternal deprivation leads to long-term alterations in hypothalamic–pituitary–adrenal (HPA) axis activity, disturbances of auditory information processing and neurochemical changes in the adult brain, some of which are similar to that observed in schizophrenia. Here we report the adult behavioural effects of maternal deprivation (12 h on postnatal days 9 and 11) in Wistar rats on paradigms of auditory information processing (prepulse inhibition), sensitivity to dopamimetics (amphetamine-induced hyper-locomotion) and cognition (T-maze delayed alternation and Morris water-maze). In addition, we examined the long-lasting effect of chronic 21-day corticosterone treatment during the post-pubertal period (i.e., postnatal days 56–76) on each of these behavioural paradigms in maternally deprived and control rats. Behavioural testing commenced 2 weeks after the termination of corticosterone treatment. Maternal deprivation led to a significant reduction in PPI and impaired spatial learning ability in adulthood, but did not affect the behavioural response to amphetamine. Post-pubertal chronic corticosterone treatment did not have any major long-lasting effects on any of the behavioural measures in either maternally deprived or control rats. Our findings further support maternal deprivation as an animal model of specific aspects of schizophrenia.

Stress, the hippocampus and the HPA axis: Implications for the development of psychotic disorders

The experience of stress is commonly implicated in models of the onset of psychotic disorders. However, prospective studies investigating associations between biological markers of stress and the emergence of psychotic disorders are limited and inconclusive. One biological system proposed as the link between the psychological experience of stress and the development of psychosis is the Hypothalamic-Pituitary-Adrenal (HPA) axis. This paper summarizes and discusses evidence supporting a role for HPA-axis dysfunction in the early phase of schizophrenia and related disorders. METHOD A selective review of psychiatric and psychological research on stress, coping, HPA-axis, the hippocampus and psychotic disorders was performed, with a particular focus on the relationship between HPA-axis dysfunction and the onset of psychotic disorders. RESULTS Individual strands of past research have suggested that the HPA-axis is dysfunctional in at least some individuals with established psychotic disorders; that the hippocampus is an area of the brain that appears to be implicated in the onset and maintenance of psychotic disorders; and that an increase in the experience of stress precedes the onset of a psychotic episode in some individuals. Models of the onset and maintenance of psychotic disorders that link these individual strands of research and strategies for examining these models are proposed in this paper. CONCLUSIONS The current literature provides some evidence that the onset of psychotic disorders may be associated with a higher rate of stress and changes to the hippocampus. It is suggested that future research should investigate whether a relationship exists between psychological stress, HPA-axis functioning and the hippocampus in the onset of these disorders. Longitudinal assessment of these factors in young people at 'ultra' high risk of psychosis and first-episode psychosis cohorts may enhance understanding of the possible interaction between them in the early phases of illness.

Problems with the coronial determination of ‘suicide’

After over 100 years of constant dissatisfaction with the accuracy of suicide data, this paper suggests that the problem may actually lie with the category of suicide itself. In almost all previous research, ‘suicide’ is taken to be a self-evidently valid category of death, not an object of study in its own right. Instead, the focus in this paper is upon the presupposition that how a social fact like suicide is counted depends upon norms for its governmental regulation, leading to a reciprocal relationship between social norms and statistical norms. Since this relationship is centred almost entirely in the coroner’s office, this paper examines governmental, definitional and categorisational issues relating to how coroners reach findings of suicide. The intention of this paper is to contribute to international debates over how suicide can best be conceptualised and adjudged.

Priority threat management of non-native plants to maintain ecosystem integrity across heterogeneous landscapes

Invasive non-native plants have negatively impacted on biodiversity and ecosystem functions world-wide. Because of the large number of species, their wide distributions and varying degrees of impact, we need a more effective method for prioritizing control strategies for cost-effective investment across heterogeneous landscapes. Here, we develop a prioritization framework that synthesizes scientific data, elicits knowledge from experts and stakeholders to identify control strategies, and appraises the cost-effectiveness of strategies. Our objective was to identify the most cost-effective strategies for reducing the total area dominated by high-impact non-native plants in the Lake Eyre Basin (LEB). We use a case study of the ˜120 million ha Lake Eyre Basin that comprises some of the most distinctive Australian landscapes, including Uluru-Kata Tjuta National Park. More than 240 non-native plant species are recorded in the Lake Eyre Basin, with many predicted to spread, but there are insufficient resources to control all species. Lake Eyre Basin experts identified 12 strategies to control, contain or eradicate non-native species over the next 50 years. The total cost of the proposed Lake Eyre Basin strategies was estimated at AU$1·7 billion, an average of AU$34 million annually. Implementation of these strategies is estimated to reduce non-native plant dominance by 17 million ha – there would be a 32% reduction in the likely area dominated by non-native plants within 50 years if these strategies were implemented. The three most cost-effective strategies were controlling Parkinsonia aculeata, Ziziphus mauritiana and Prosopis spp. These three strategies combined were estimated to cost only 0·01% of total cost of all the strategies, but would provide 20% of the total benefits. Over 50 years, cost-effective spending of AU$2·3 million could eradicate all non-native plant species from the only threatened ecological community within the Lake Eyre Basin, the Great Artesian Basin discharge springs. Synthesis and applications. Our framework, based on a case study of the ˜120 million ha Lake Eyre Basin in Australia, provides a rationale for financially efficient investment in non-native plant management and reveals combinations of strategies that are optimal for different budgets. It also highlights knowledge gaps and incidental findings that could improve effective management of non-native plants, for example addressing the reliability of species distribution data and prevalence of information sharing across states and regions.

Priority threat management of invasive animals to protect biodiversity under climate change

Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one-sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost-effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost-effectiveness was relatively unaffected by including climate change into decision-making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected.

Inside the black box of food safety: A qualitative study of ‘non-compliance’ among food businesses

Issue addressed The paper examines the meanings of food safety among food businesses deemed non-compliant and considers the need for an ‘insider perspective’ to inform a more nuanced health promotion practice. Methods In-depth interviews were conducted with 29 food business operators who had been recently deemed ‘non-compliant’ through Council inspection. Result Paradoxically, these ‘non-compliers’ revealed a strong belief in the importance of food safety as well as a desire to comply with the regulations as communicated to them by Environmental Health Officers (EHOs). Conclusions The evidence base of food safety is largely informed by the science of food hazards, yet there is a very important need to illuminate the ‘insider’ experience of food businesses doing food safety on a daily basis. This requires a more socially nuanced appreciation of food businesses beyond the simple dichotomy of compliant/ non-compliant. So what? Armed with a deeper understanding of the social context surrounding food safety practice, it is anticipated that a more balanced, collaborative mode of food safety health promotion could develop which could add to the current signature model of regulation.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Acquaintance or partner? Social economy organisations, institutional logics and regional development in Australia

The social economy as a regional development actor is gaining greater attention given its purported ability to address social and environmental problems. This growth in interest is occurring within a global environment that is calling for a more holistic understanding of development compared to traditionally economic-centric conceptions. While regional development policies and practices have long considered for-profit businesses as agents for regional growth, there is a relatively limited understanding of the role of the social economy as a development actor. The institutional environment is a large determinant of all kinds of entrepreneurial activity, and therefore understanding the relationships between the social economy and broader regional development processes is warranted. This paper moves beyond suggestions of an economic-centric focus of regional development by utilising institutional logics as a theoretical framework for understanding the role of social enterprise in regional development. A multiple case study of ten social enterprises in two regional locations in Australia suggests that social enterprise can represent competing logics to economic-centric institutional values and systems. The paper argues that dominant institutional logics can constrain or promote the inter-play between the social and the economic aspects of development, in the context of social enterprise.

Planning for pandemics: Lessons from the past decade

It is now 10 years since the disease we now know as SARS-severe acute respiratory syndrome-caused more than 700 deaths around the world and made more than 8,000 people ill. More recently, in 2009 the global community experienced the first influenza pandemic of the 21st century-the 2009 H1N1 influenza pandemic. This paper analyses the major developments in international public health law relating to infectious diseases in the period since SARS and considers their implications for pandemic planning.