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Self-compassion constitutes a positive way of relating towards the self that enables emotional regulation and reduces emotional distress. This research first explored differences among a sample of persons with social anxiety disorder (SAD) and groups of high socially anxious (HSA) and low socially anxious (LSA) students on self-compassion, emotion regulation, and social anxiety. We then investigated emotional regulation as a mediator of the prediction of social anxiety by self-compassion and the influence of depressed mood on those relationships.Study 1 compared a SAD group to matched groups of HSA and LSA students. Study 2 utilized the total sample (n = 330 students and n = 33 SAD) to test mediation. Self-compassion and emotion regulation were predictors of social anxiety and depression a covariate.In Study 1, the SAD group did not differ from the HSA group on most aspects of self-compassion and emotional regulation but was higher on depression. Both were lower on most measures and higher on depression than the LSA group. In Study 2, higher self-compassion predicted lower social interaction anxiety, and emotional regulation strategies mediated this effect, regardless of depression. However, for social performance anxiety, controlling for depression removed mediation. Refraining from uncompassionate responses was directly connected to social anxiety, whereas compassionate responses influenced social anxiety via emotional regulation.Results affirm the ameliorative role of self-compassion on social anxiety and emotion regulation strategies as mechanisms of that influence. However, self-compassion's influence was affected by depression and type of social anxiety. Also, refraining from uncompassionate self-responding appears to be of prime importance in predicting social anxiety, whereas compassionate self-responding influences social anxiety via emotion regulation.

Sf6 is a bacterial virus that infects the human pathogen Shigella flexneri. Here, we describe the cryo–electron microscopy structure of the Sf6 tail machine before DNA ejection, which we determined at a 2.7-angstrom resolution. We built de novo structures of all tail components and resolved four symmetry-mismatched interfaces. Unexpectedly, we found that the tail exists in two conformations, rotated by ~6° with respect to the capsid. The two tail conformers are identical in structure but differ solely in how the portal and head-to-tail adaptor carboxyl termini bond with the capsid at the fivefold vertex, similar to a diamond held over a five-pronged ring in two nonidentical states. Thus, in the mature Sf6 tail, the portal structure does not morph locally to accommodate the symmetry mismatch but exists in two energetic minima rotated by a discrete angle. We propose that the design principles of the Sf6 tail are conserved across P22-like Podoviridae.

Purpose The purpose of this study is to investigate the experiences of staff during the development and implementation of an Australian-first, family-focussed service addressing the mental health needs of young people (aged 12–25 years) with an intellectual disability. This study aims to understand the challenges and successes of the staff team when navigating their way in a new program working with a complex client group. Design/methodology/approach This study used a thematic analysis on data collected from focus groups at two time points in the implementation phase of the new program. Thematic analysis of the data was conducted to identify important themes relating to the staff’s challenges, successes and learning. Findings The findings showed that there was a lot of adaptation needed for staff members trained in either mental health, or disability, but not both. Another key finding was the importance of working with the young person’s family system as well as their existing system of support services. This major focus of the work for staff could be challenging due issues arising in the family unit and a lack of collaboration between services. Working with this complex client group was viewed as challenging and stress inducing; however, the motivation and attitudes of staff were found to be positive factors in the running of the program. Originality/value This paper makes an original contribution to the field, as it provides a unique look at staff experiences when needing to adapt to a new and challenging workplace that was the first-of-its-kind in Australia.

Objective Current competencies required for fellowship of the RANZCP require psychiatry registrars to have experience in working with clients across all age groups, as well as working with families and the client’s wider network, however gaining this experience is not always easy for trainees. This paper reports on the experience of participating in Single Session Family Therapy (SSFT) during registrar training as a different modality for learning. Method: An online survey was conducted with fourteen registrars who had participated in SSFT during their child and adolescent rotation. Qualitative and simple quantitative data were collected and analysed. Results: Participating in SSFT during training was initially daunting, but had a positive effect on trainees, including influencing some towards focussing their future sub-specialisation in the child and youth area. Experience came through learning by doing, and seeing change. Registrars learnt about: understanding the role of the family; teamwork; technical skills; and gained confidence. Conclusions: Opportunities for trainees to participate in SSFT enables powerful learning beyond what can be taught in the classroom. Such opportunities may enhance registrars’ perceptions of family work, and may positively influence decision about future sub-specialisation.

Objectives Self-compassion represents a way of interacting with the self involving kindness and a balanced approach to negative self-related stimuli that has shown to contribute to reduced depression, anxiety and stress, and increased psychological well-being. Due to the potential barriers towards self-compassion for people with depressive symptoms, the objective of the present study what to investigate whether the emerging construct of 'nonattachment to self', which reflects a flexible and balanced approach to all self-related stimuli, may be more beneficial for positive psychological outcomes than self-compassion, for individuals with depressive symptoms. Method A sample 388 participants (consisting of 71 men, 317 women) aged from 18 to 77 (M = 35.33, SD = 10.81) completed an online questionnaire measuring levels of self-compassion, nonattachment to self, depressive symptoms, and well-being. Results Higher levels of both nonattachment to self and self-compassion were related to reduced psychological distress and increased psychological well-being. However, for people with at least mild depressive symptoms, nonattachment to self was found to be a stronger predictor of reduced psychological distress and increased psychological well-being than self-compassion. Conclusion In conclusion, the present study suggests both nonattachment to self and self-compassion are associated with better mental health in non-clinical populations. Further, for individuals experiencing at least mild symptoms of depression, self-compassion may be less beneficial than taking a more nonattached stance towards the self. The findings have implications for the way we conceptualize self-focused attention and suggest assisting individuals to let go of their fixated, self-focused attention may be especially beneficial for individuals with depressive symptoms. Practitioner points The notion of letting of attachment to the separate static self lies at the core of Buddhist psychological teachings and recent research suggests it can have a positive impact on individuals psychological well-being and ill-being Given the barriers to self-compassion experienced by individuals with depressive symptoms, nonattachment to self may represent a healthy interaction with the self than is met with less resistance than self-compassion. Due to the balanced stance of nonattachment to self towards positive and negative self-related stimuli, it may be prove to be a valuable approach to treating individuals who feel conflict with taking any form of positive or kind stance towards the self.

Mindful attention appears to facilitate greater satisfaction of basic psychological needs (i.e., autonomy, competence, and relatedness). Recent findings suggest that nonattachment may arise from mindfulness, with nonattachment being found to mediate relationships between mindfulness and various outcomes, such as increased wellbeing. Across two undergraduate samples, nonattachment was found to partially mediate relationships between mindful attention and the perceived satisfaction of each of autonomy, competence, and relatedness with others (N = 247), and greater relative autonomous motivation for study (N = 578). The findings therefore support and extend on existing research related to mindful attention within the Self-Determination Theory literature while also adding to the growing literature on the apparent benefits of nonattachment. Future research on autonomous motivation and basic need satisfaction may therefore benefit from considering nonattachment alongside mindful attention.

Materialism has often been considered as a means of attaining a more positive sense of self within a consumer culture. In two undergraduate samples (N = 248, 183), the current study assessed the extent to which various forms of insecurity (i.e., low self-esteem, public self-consciousness, relative deprivation, anxious attachment, fear of death) mediate the relationship between the Buddhist construct of nonattachment and materialism. In line with expectations, greater nonattachment was directly associated with reduced materialism in both samples. Nonattachment was also found to be indirectly associated with reduced materialism via reduced public self-consciousness and relative deprivation. Self-esteem, anxious attachment, and fear of death did not mediate the relationship between nonattachment and materialism. The findings therefore indicate that the acceptance and non-contingent sense of self typical of nonattachment may play an important role in minimising the experience or impact of insecurity that can contribute to materialism, as well as minimising the importance placed on material goals.

Previous research has indicated that nonattachment mediates the relationship between mindfulness and the ability to be adaptable. Additionally, adaptability has been associated with increased acade...

Psychological development continues throughout adulthood, with some individuals reaching advanced levels of adult psychological development. A focus of the present study was to investigate the Buddhist construct of nonattachment in relation to three elements of advanced psychological development: wisdom, self-actualisation and self-transcendence. The possibility that nonattachment mediates the relationship of mindfulness to these aspects of optimal psychological development was also investigated. Results from 348 university students supported expectations that nonattachment was positively related to wisdom, self-actualisation and self-transcendence and confirmed similar positive relationships for mindfulness. In addition, nonattachment was found to act as a partial mediator of mindfulness for all three aspects of advanced adult psychological development. Interestingly, an alternate mediational pathway was discovered as mindfulness was shown to mediate the relationship of nonattachment to measures of advanced psychological development. The results have implications for understanding the different pathways towards developing wisdom, self-actualisation and self-transcendence and provide insight into the possible mechanisms of mindfulness and nonattachment that help to explain their positive impact.

The Buddhist concept of nonattachment refers to a flexible engagement with experience without fixation on achieving specified outcomes. The primary focus of this study was to qualitatively examine ...

Background Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. Objective Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. Methods Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. Results Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. Conclusion D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

While child sexual abuse is a problem worldwide, the risk factors for the perpetration of child sexual abuse within Fiji are unique in their relation to the traditional and communal nature of Fijian society. In this article, culturally relevant dynamic risk factors found within contemporary Fijian society are identified and understood alongside static factors contributing to abuse. Although there have been recent changes to sexual offence legislation and traditional criminal justice system responses to victims of sexual abuse, state-sanctioned responses continue to maintain victimising practices. Equally, the relative rural isolation means many Indigenous Fijian (iTaukei) communities continue to use customary restorative justice practices that may marginalise the rehabilitation of victims and offenders for the communities' benefit. However, a culturally specific amalgamation of traditional criminal justice and customary restorative responses may help to create more holistic protection for survivors of child sexual abuse in Fiji. Language: en

This thesis creates a better understanding of how culture influences the Fijian criminal justice systems responses to sexual victimisation and offending, and argues that these is a space for customary responses to sexual offences. However, this should not be in the form of the current bulubulu (the customary reconciliation ceremony of the iTaukei people\Indigenous Fijians) ceremony.

Transformational processing refers to the extent to which individuals openly explore, resolve, and personally grow from their life experiences so that these experiences become transformative. The present study explored whether the transformational processing of peak experiences (TPpeak) and of nadir experiences (TPnadir) related to eudaimonic well-being (psychological well-being) and hedonic well-being (subjective well-being). A sample of 116 respondents (76 women, 40 men) provided detailed descriptions of a peak and nadir experience, and how these experiences had changed their lives. As predicted, transformational processing of peak experiences and of nadir experiences was significantly related to eudaimonic and hedonic well-being, but only the transformational processing of nadirs significantly reduced negative affect. TPnadir and TPpeak did not differ in the strength of correlation with eudaimonic or hedonic well-being, and each made a unique contribution to eudaimonic well-being. However, only TPnadir made a unique contribution to hedonic well-being. Findings suggest that increased hedonic well-being requires a focus on working through the most difficult times in life, but for eudaimonic well-being, a focus on working through extremely negative and positive life experiences is beneficial.

Recent research has indicated that the Buddhist construct of nonattachment is associated with greater psychological wellbeing (i.e., flourishing). It has also been found that flourishing contributes to greater academic success. In a multidisciplinary first year undergraduate sample (N = 389) the current study provided the first evidence that higher levels of nonattachment were weakly indirectly associated with higher grades via the flourishing facets of environmental mastery and personal growth. Contrary to expectations, nonattachment was directly associated with lower grades and was also indirectly associated with lower grades due to a negative relationship between the flourishing facet of positive relationships and grades. The findings therefore suggest that nonattachment may help to facilitate perspectives that contribute to academic success. While further research is required, nonattachment may also concurrently reduce a focus on grades, potentially encouraging some students to pursue challenging courses where their grades may not be as high.

Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools.35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images.The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow.This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Background Creative use of legislation can produce positive change in the lives of people with intellectual disabilities. This may be ‘bottom-up’ or ‘top-down’ or at multiple levels and with multiple stakeholders. Method Using a human rights–based approach (HRBA), four initiatives to improve services for people with intellectual disabilities in the UK are described. Results The first example explains the process of co-producing a DVD and board game to enable people with intellectual disabilities to understand their human rights. The second example considers the impact of organizational culture in the process of embedding a pilot evaluation of practical, human rights–based risk assessment and management tools. A third pilot project examines how the guiding principles of Mental Health Act (MHA) (2007) for England and Wales can be operationalized using an HRBA. Finally, improving equitable access to health care through a ‘top-down’ process of change involving the Green Light Toolkit is reported. Conclusion The authors consider how to approach the process and where to focus in the system, to realize meaningful change.

While regimes in countries like Cameroon, Guinea, Togo and Tanzania have survived the transition from single to multiparty rule, this article suggests two unique characteristics for the case of regime tenure in Tanzania. First, while transitions in other cases were characterized by widespread protests and/or popular opposition movements, opposition in Tanzania's transition environment was minuscule by comparison. Secondly, while repression is still widespread in Tanzania, overt repression appears to be less prevalent in Tanzania when compared to most other strong tenure cases. This study first explores the comparative role of overt repression as a viable explanation for the strong tenure of the Chama Cha Mapinduzi (CCM). Upon closer examination, however, the article argues that accounting for the structures and processes that shape the capacities of political actors to engage in political battles might provide for a more complete appreciation of the CCM's ability to remain the country's dominant political...

Accessible summary • When people are risk assessed, they are sometimes denied their human rights. • In this paper, we say that if we balance the human rights of service users,1 their carers and people in their community we can manage risk much better. • This means that people who use services are involved in their own risk assessments. • It also means people’s human rights are looked at in the way they are supported. Summary Recent reports highlight the extent to which many people with learning disabilities are not afforded access to their basic human rights. In addition, traditional approaches to risk management often focus on professional assessments of risks and challenging behaviour and exclude service user perspectives. In this paper, we outline what we believe to be the key principles of a human rights-based approach (HRBA) to risk assessment and management. We argue that if we balance the human rights of service users, their carers and members of their communities, we can, in effect, manage risk within a much more positive paradigm. A HRBA to risk emphasises service user inclusion, recognises the impact of diverse identities on risk behaviours and makes the human rights in risk management decisions explicit. We believe a human rights approach offer a coherent unifying framework for much current best practice; prompting all involved to design proactive, proportional risk management strategies which balance the rights involved in the person’s risky behaviours with the rights involved in the management strategy. The tools we have developed within our service, structuring a HRBA to risk assessment and management, are briefly presented. Case examples are included to illustrate key points.

Assess the association of schizophrenia patients' perceived copayment burden with medication adherence and outcomes.Patients with schizophrenia (aged 18+) completed self-reported questionnaires. Analyses included those currently using a second-generation antipsychotic (SGA) with no exposure to clozapine or depot formulation antipsychotics. Adherence was assessed using the Morisky Medication Adherence Scale (MMAS). Outcomes included emergency room (ER) use, hospitalization, attempted suicide, missed work due to health, and experiencing severe psychological distress. Logistic regression was used to adjust for demographics, health characteristics, psychotropic medication use, and insurance status.Of 351 schizophrenia patients, 39% perceived copayment burden. These patients were less than half as likely to have complete adherence [OR = 0.427; 95% CI:0.257, 0.711; p = 0.001] Copayment burden was associated with greater likelihood of ER use, [OR = 2.157; 95% CI:(1.322, 3.520); p = 0.002], hospitalization [OR = 2.512; 95% CI: (1.475, 4.277); p0.001], attempted suicide[OR = 2.385; 95% CI: (1.156, 4.920); p = 0.019], severe psychological distress [OR = 1.833; 95% CI:1.092, 3.075; p = 0.022] and greater likelihood of missing work [OR = 7.193; 95% CI: 2.554, 20.256; p0.001].Copayment burden is associated with poorer medication adherence and outcomes. Formularies that reduce copayment burden for SGAs may positively affect medication adherence and outcomes among schizophrenia patients.Patient data were self-reported, which may have introduced additional bias in the study measures. Also, the use of a cross-sectional design precludes causal inference and the use of the current sampling methodology (both interview and Internet panel) might impact the ability to generalize the results to the broader population.

Background: Since their introduction, second-generation antipsychotics (SGAs) have become the drugs of choice for the treatment of schizophrenia. However, recent findings have questioned the benefits of SGAs over first-generation antipsychotics (FGAs). Objective: This post hoc analysis sought to compare the utility of the SGA aripiprazole with the FGA haloperidol in patients with early-phase schizophrenia (ES) or chronic schizophrenia (CS). Method: Data were pooled from two identical 52-week, randomized, active comparator trials (31-98-217 and 31-98-304) of aripiprazole 20-30 mg/day versus haloperidol 7-10 mg/day. Patients in the efficacy sample were classified as having ES if they were ≤40 years of age with a duration of illness ≤5 years. All other patients were classified as having CS. Health-state utilities were derived from the Positive and Negative Syndrome Scale and adverse events, using the last observation carried forward method. Results: Of 1294 patients in the efficacy sample, 362 met criteria for ES (aripiprazole, n - 239; haloperidol, n - 123) and 932 met criteria for CS (aripiprazole, n - 622; haloperidol, n - 310). Baseline patient characteristics were similar between treatment arms. At week 52, patients treated with aripiprazole in the total and ES populations had significantly greater total utility than those treated with haloperidol, although there were no statistically significant differences in total utility for the CS population at week 52. For the total population, patients treated with aripiprazole had significantly higher quality-adjusted life days (QALDs)/year than haloperidol recipients (+6.48 QALDs/year, p - 0.02). Significantly higher QALDs/year were also seen for aripiprazole-treated patients with ES (+10.65 QALDs/year, p - 0.04) but not for patients with CS (+4.92 QALDs/year, p - 0.14), compared with haloperidol-treated patients. Conclusions: Aripiprazole demonstrates greater utility than haloperidol over 52 weeks of treatment. This difference was driven by superiority of aripiprazole over haloperidol in patients with ES, which was not observed in patients with CS.

The medical information department within a pharmaceutical company functions to provide concise, consistent, and appropriate information and customer service to external and internal customers, while maintaining effective and quality-controlled processes. These medical information departmental goals become more challenging when two companies form a partnership, because of the complexity of additional staff members with varying goals and objectives involved in joint venture projects. The objective of this article is to review how two medical information groups function within a pharmaceutical alliance, and examine changes in the partnership that occurred in the different stages of the drug product life cycle. This is the first published article on the late-phase maintenance of a pharmaceutical alliance in medical information.

Objective To examine the efficacy of aripiprazole across symptoms in patients with acute exacerbation of schizophrenia or schizoaffective disorder. Methods Data were pooled from five, 4–6-week acute studies. PANSS Total, Positive, Negative, and General Psychopathology Subscale improvements were analyzed, as well as all 30 individual PANSS items. Results Aripiprazole had statistically significant decreases versus placebo on PANSS subscales at Week 4, similar to those seen with haloperidol. Aripiprazole-treated patients also showed significant decreases versus placebo in 26 of the 30 PANSS items (all p Conclusion Aripiprazole demonstrates statistically and clinically significant efficacy across a range of symptoms in schizophrenia.

Purpose This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). Methods The study population included patients of 18–64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the “control index date” was the date of claim if there was only a single medical claim; for patients with ≥2 claims, one was selected at random as the “control index date.” Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent) – aripiprazole/ziprasidone; medium – risperidone; high – olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. Results Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03–1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83–1.64) and 1.17 95%CI (0.79–1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15–2.25) and 1.25 95%CI (0.89–1.74), respectively. Conclusions High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence. Copyright © 2008 John Wiley & Sons, Ltd.

Background: Individuals with mental illness are at a higher risk of medical mortality than the general population, primarily due to an increased risk of cardiovascular disease. There are a number of modifiable metabolic risk factors associated with some atypical antipsychotics that warrant careful monitoring and treatment in both psychiatric and primary care practice if the risk of cardiovascular disease is to be effectively reduced. Data Sources: Previous guidelines have focused on awareness of metabolic risk factors in psychiatry, yet few articles have appeared in the primary care–focused journals. We present pragmatic guidelines that focus on monitoring metabolic abnormalities in primary care based on established guidelines, including joint recommendations of the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity, and the Mount Sinai conference. Data Synthesis: All patients receiving atypical antipsychotic agents associated with metabolic adverse events should be routinely monitored for weight gain and abnormalities in blood glucose and lipid levels. Effective communication and collaboration between mental health and primary care services and better access to primary care screening and treatment for individuals with mental health problems are needed. Conclusion: There is a clear need for awareness among primary care physicians, particularly as metabolic effects of atypical antipsychotics such as blood pressure and glucose and lipid levels are possibly best monitored in a primary care setting.

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation.

In the primate cerebral cortex, morphologically and functionally diverse classes of local circuit neurons containing the inhibitory neurotransmitter γ-aminobutyric acid (GABA) differentially regulate the activity of pyramidal cells, the principal type of excitatory output neurons. In schizophrenia, GABA neurotransmission in the prefrontal cortex (PFC) appears to be disturbed but whether specific populations of GABA neurons are affected is not known. The chandelier class of GABA neurons are of particular interest because their axon terminals, which form distinctive arrays termed “cartridges,” provide inhibitory input exclusively to the axon initial segment of pyramidal cells. Thus, chandelier cells are positioned to powerfully regulate the excitatory output of pyramidal neurons and, consequently, to substantially affect the patterns of neuronal activity within the PFC. In this study, an antibody directed against the GABA membrane transporter GAT-1 was used to label GABA axon terminals in postmortem human brains. The relative density of GAT-1-immunoreactive axon cartridges furnished by chandelier neurons was decreased by 40% in the PFC of schizophrenic subjects compared with matched groups of normal control and nonschizophrenic psychiatric subjects. In contrast, markers of the axon terminals of other populations of GABA neurons were not altered in the schizophrenic subjects. Furthermore, the density of GAT-1-immunoreactive axon cartridges was not altered in psychiatric subjects who had been treated with antipsychotic medications. The changes in GAT-1-immunoreactive axon cartridges of chandelier neurons in schizophrenia are likely to reflect altered information processing within the PFC and in its output connections to other brain regions and could contribute to the cognitive impairments seen in this disorder.

Recent studies have reported that acute administration of dopamine D2 receptor antagonists increases expression of the immediate early gene c-fos in the rat striatal complex. There have been no corresponding studies of the effects of D2 antagonists in primate species. Since all clinically effective antipsychotic drugs share D2 receptor antagonism, it is important to define the extent to which these drugs may alter expression of c-fos or its protein product, Fos, in primates. We therefore examined the effects of administration of two D2 receptor antagonists, haloperidol and metoclopramide, on Fos expression in the striatum and temporal cortices of the vervet monkey. Metoclopramide does not appear to possess significant antipsychotic efficacy but potently produces extra-pyramidal side effects, while haloperidol is an effective antipsychotic drug that produces extrapyramidal side effects. Both drugs increased the number of Fos-like immunoreactive (Fos-li) neurons in the caudate nucleus and putamen; the numbers of Fos-li neurons in these regions were increased in both the patch and matrix compartments. Haloperidol but not metoclopramide increased the number of Fos-li neurons in the nucleus accumbens shell. Similarly, haloperidol but not metoclopramide increased the number of Fos-li neurons in the entorhinal cortex. Neither drug altered Fos expression in the inferior temporal cortex. These data suggest that the dorsolateral caudate nucleus and putamen may be sites at which D2 receptor antagonists elicit extrapyramidal side effects, and the nucleus accumbens shell and entorhinal cortex may be loci at which the therapeutic actions of antipsychotic drugs are manifested.

To assess the relationship between patient cost-sharing (e.g., copayments or coinsurance) and adherence and persistence to second-generation (atypical) antipsychotic (SGA) medications.A retrospective, observational study of adults aged 18-64 years with schizophrenia or bipolar disorder (n = 7,910) who initiated SGA medications with employer-sponsored insurance in the 2003-2006 MarketScan Commercial Claims and Encounters Database. Adherence was defined as percent of days covered in each calendar quarter. Persistence was defined as days from initiation of SGA to the first 90-day gap in medication on-hand. Generalized Estimating Equations were used to determine the effects of cost-sharing on adherence to SGA medications based on patient-quarter data. A Cox proportional hazards model with patient cost-sharing as a time-varying covariate estimated the effects on persistence with SGA medication.Higher cost-sharing was associated with a lower likelihood of adherence. When compared to plans with cost-sharing below $10, adherence rates were approximately 27% lower for patients in plans with SGA cost-sharing of $50 and above and about 10% lower for patients in plans with cost-sharing between $30 and $50. In both cases, the reduction in adherence was significant. Higher cost-sharing was also associated with a shorter time to discontinuation (HR: 1.028; 95% CI [1.006-1.051]).High SGA cost-sharing appears to be a financial barrier to SGA medication compliance, especially when cost-sharing levels exceeded $30. Our findings have implications for health plans, employers, and policymakers who have, or are, contemplating establishing cost-sharing tiers for SCA medications for commercially insured patients with serious mental illnesses.

This post hoc analysis evaluated the effects of aripiprazole on Positive and Negative Syndrome Scale (PANSS) Hostility factor scores in adolescents with schizophrenia.In total, 302 adolescents (13-17 years) with schizophrenia were enrolled in a 6-week, multicenter, double-blind, randomized, placebo-controlled trial comparing aripiprazole (10 or 30 mg/day) with placebo. The PANSS was the primary outcome measure. To determine the effect of aripiprazole on hostility, a post hoc analysis of the PANSS Hostility factor and individual items was performed.Aripiprazole was superior to placebo in reducing PANSS Hostility factor scores in adolescents with schizophrenia. After 6 weeks, aripiprazole 10 mg/day and aripiprazole 30 mg/day showed a statistically significant improvement versus placebo (-3.0, -3.7, versus -2.1; p0.05; last observation carried forward [LOCF]) in the PANSS Hostility factor. For aripiprazole 30 mg/day, statistically significant separation from placebo was evident from week 3 through week 6 and at week 6 for aripiprazole 10 mg/day. Individual PANSS Hostility, Uncooperativeness, and Poor Impulse Control Items showed statistically significant improvement with aripiprazole 30 mg/day over placebo at end point.This post hoc analysis shows that aripiprazole (10 and 30 mg/day) is an effective treatment for hostility symptoms in adolescents with schizophrenia. Clinical trials information: ClinicalTrials.gov identifier: NCT00102063.

Recent literature and government guidance has highlighted the rights of parents with leaming disabilities and role of services in meeting their needs. In the present study, three focus groups were conducted involving 35 members of community health visiting teams in order to identify estimated incidence and needs of parents with learning disabilities and the needs of services in supporting them. The health visiting teams identified clinically significant numbers of parents with learning disabilities and--through qualitative focus group discussion--suggested a significant need for intervention and support for these parents, greater resources and knowledge within health visiting services, and improved interagency co-ordination and communication.

Bipolar disorder is a chronic condition characterized by the recurrence of episodes of manic, hypomanic, depressive, and mixed states.1 The lifetime prevalence of bipolar disorder has been estimated to be 1%, although recent evidence suggests that the prevalence may be as high as 5% when applying broader definitions that encompass the entire bipolar spectrum.2,3 Worldwide, bipolar disorder is the sixth leading cause of medical disability among patients aged 15 to 44 years.1 The annual cost of bipolar disorder in the United States in 1991 was estimated to be $45 billion, $7 billion of which was direct costs and $38 billion was indirect costs, including lost productivity of patients and caregivers.1 Lost productivity alone may account for up to $14.1 billion among employed patients.3 Current pharmacologic interventions for bipolar disorder include lithium, anticonvulsant agents, and second-generation antipsychotic medications.4,5 As in many chronic disease states with intermittent symptoms, medication nonadherence is a common occurrence in bipolar disorder5 and is associated with poorer outcomes.6–10 One survey found that 34% of respondents with bipolar disorder reported missing at least 1 dose of psychotropic medication in a 10-day period.11 Studies of veterans with bipolar disorder found even higher rates of nonadherence at approximately 45.9% among those taking lithium or anticonvulsant agents12 and 48.1% among those taking antipsychotic medications.13 Nonadherent patients with bipolar disorder are at a greater risk of suicide,6,7 experience shorter duration between episodes, and are more likely to relapse,8,9 resulting in higher total medical expenditures and higher outpatient mental health care costs.10 Multiple sociodemographic factors have been associated with nonadherence in bipolar disorder, including gender,14 age,11 race,14,15 and education level.15 In addition, clinical factors such as alcohol dependence,11,14 comorbid affective disorders,11 manic episodes,14 and severity of depressive episodes15 are associated with poorer adherence. However, because medication nonadherence is a behavioral symptom related to specific decisions made by patients, patient-centered experiences should also be considered. Patient satisfaction with medication is a significant predictor of better adherence,14,15 whereas side effects such as cognitive impairment,15 extrapyramidal symptoms, sedation, sexual dysfunction, and weight gain are associated with poorer adherence.15,16 Clinical Points ♦ Nonadherence is common among patients with bipolar disorder. ♦ Several risk factors for nonadherence have been identified, including low medication satisfaction, a high number of medications, and psychic side effects. ♦ By assessing tolerability and side effects, physicians may help to assist patients to improve adherence and health outcomes. To date, research on medication nonadherence in bipolar disorder has been limited to narrow subpopulations such as veterans or patients recently discharged from the hospital. The primary objective of this survey study was to identify and describe drivers of medication adherence in a large, national sample of outpatients with bipolar disorder.

The authors sought to quantify plasma lipid and glucose testing rates in patients receiving second-generation antipsychotics before and after guidelines recommending testing were issued in February 2004 by the American Diabetes Association (ADA).In this retrospective cohort analysis using data from a large managed care database (PharMetrics, 2000-2006), patients under age 65 on second-generation antipsychotics were identified and followed from 40 days before to 130 days after the antipsychotic prescription was written. Baseline and 12-week (40 days) lipid and glucose testing rates were determined for pre- and postguideline cohorts. Logistic regression analyses determined predictors of baseline and 12-week lipid and glucose testing while controlling for covariates.A total of 5,787 preguideline patients and 17,832 postguideline patients were identified. Baseline lipid testing rates were 8.4% for the preguideline cohort and 10.5% for the postguideline cohort, and the 12-week testing rates were 6.8% and 9.0%, respectively. Baseline glucose testing rates were 17.3% for the preguideline cohort and 21.8% for the postguideline cohort, and the 12-week testing rates were 14.1% and 17.9%, respectively. All four comparisons were statistically significant. Baseline and 12-week testing rates for lipids and glucose in children were the lowest of all age groups.Despite statistically significant improvements after the ADA guidelines were issued, monitoring for plasma lipids and glucose in this population remains low. Clinicians and administrators responsible for the health of at-risk populations should implement new approaches for effective monitoring of major modifiable risk factors for medical morbidity and mortality in patients taking second-generation antipsychotics.

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p

Objective Race is strongly associated with risk for metabolic dysfunction, but there is limited prospective data concerning the impact of race on antipsychotic metabolic outcomes among patients with schizophrenia. Method This study is a post hoc analysis of data from a 26-week, double-blind, randomized trial of aripiprazole (N = 155) and olanzapine (N = 159) conducted from April 2000 through June 2001 in patients aged >or= 18 years with acute schizophrenia according to DSM-IV criteria. The data were analyzed on the basis of racial breakdown: white and black/Hispanic. Between-drug and within-drug outcomes were analyzed separately for each racial cohort across weight, lipid, and glucose parameters. Results For white subjects (N = 167), olanzapine significantly worsened all metabolic parameters except high-density lipoprotein (HDL) cholesterol and fasting glucose, and this was significantly different than aripiprazole for every outcome except fasting glucose. In the black/Hispanic cohort (N = 137), olanzapine treatment resulted in adverse metabolic outcomes, and these changes were significantly different from aripiprazole for adiposity, total cholesterol, and non-HDL cholesterol. Aripiprazole decreased the odds of endpoint metabolic syndrome compared with olanzapine for all subjects (OR = 0.33, 95% CI = 0.19 to 0.55), the white cohort (OR = 0.20, 95% CI = 0.10 to 0.41), and black/Hispanic subjects (OR = 0.53, 95% CI = 0.25 to 1.12), but the black/Hispanic result was not statistically significant (p = .096). Within the aripiprazole group, white subjects had significantly lower risk for metabolic syndrome, but there was no significant difference in metabolic syndrome between white and black/Hispanic subjects exposed to olanzapine. Conclusions Race may be an important moderator of metabolic risk during atypical antipsychotic therapy. Olanzapine treatment is associated with greater effects on adiposity and lipids than aripiprazole in both white and black/Hispanic subjects, suggesting that antipsychotic choice and intensive monitoring are important in minimizing metabolic risk, especially in nonwhite patients.

Objective: Aripiprazole is a second-generation antipsychotic that is increasingly prescribed in a variety of psychiatric disorders. The goal of this study was to investigate patient and treatment factors associated with aripiprazole treatment continuation on hospital discharge in psychiatric inpatients. Method: This was a retrospective cohort analysis of patients admitted to a psychiatric hospital between January 1, 2003, and June 30, 2006, and treated with aripiprazole. The goal was to determine factors associated with continuation of aripiprazole throughout the hospital stay and on discharge from the hospital. Covariates assessed included patient demographics, prior psychiatric hospitalizations, diagnoses, prior antipsychotic use, and concomitant psychotropic medications. Aripiprazole-specific covariates were starting and maximum dose and dose titration pattern. Diagnoses were identified using ICD-9-CM codes. Results: There were 1957 aripiprazole-treated patients included in this study, and 1573 (80%) continued aripiprazole treatment at the time of hospital discharge. Median starting doses were lower (5 mg/day) for younger and older patients, and patients with psychotic disorders received higher doses than other patients. Approximately 58% of patients had at least 1 aripiprazole dose titration while hospitalized, and most (73%) of those patients had a dose titration within 3 days of admission. Predictors of treatment continuation in this broad patient population were younger age, a diagnosis of bipolar or major depressive disorder, higher maximum aripiprazole doses, and upward dose titration within 3 days of admission. Patients receiving concomitant anticholinergics or antipsychotics were less likely to continue treatment as were those receiving aripiprazole at the time of hospitalization. Conclusion: In this acute inpatient psychiatric setting, continuation of aripiprazole treatment on discharge was achieved in most patients. Demographic, diagnostic, and treatment factors predicting aripiprazole treatment effectiveness were identified. (J Clin Psychiatry 2008;69:1393‐1397)

This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI).The study population included patients of 18-64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients withor =2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent)--aripiprazole/ziprasidone; medium--risperidone; high--olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis.Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03-1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83-1.64) and 1.17 95%CI (0.79-1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15-2.25) and 1.25 95%CI (0.89-1.74), respectively.High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence.

BACKGROUND We tested the hypothesis that individuals carrying low-function alleles of the serotonin transporter (5-HTTLPR) and 5-HT(2A) receptor gene (-1438G/A) promoter polymorphisms would show relatively poor treatment responses on indices of bulimic and concurrent symptoms. METHOD Participants included 111 women with bulimia-spectrum eating disorders (DSM-IV-TR criteria), 98 of whom were followed through 4- to 8-month spans of specialized multimodal treatment to enable examination of relationships between genotypes and prospective changes in eating and general psychiatric symptoms. Given a hierarchically structured dataset and a desire to control for effects of variations in adjunctive pharmacotherapy, individual therapy, group therapy, or day treatment, we used multilevel modeling techniques. The study was conducted between October 2001 and May 2007. RESULTS After effects of treatments were removed, 5-HTTLPR low-function allele carriers showed smaller treatment reductions in binge eating (p < .01) and in anxiety and depression (p < .05), whereas low-function -1438G/A G carriers showed smaller reductions in binge eating (p < .01) and impulsivity (p < .05). CONCLUSIONS This study documents an expected association between poorer bulimia-treatment response and low-function alleles of 5-HTTLPR and -1438G/A--and suggests that such effects cannot be attributed to mediating influences of medication or psychotherapy responsiveness alone. A better understanding of hereditary, serotonin-mediated factors affecting bulimic individuals' progress during therapy may facilitate the development of more effective treatments.