99 research outputs found

    Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

    Get PDF
    Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression.C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS

    Quality of life of Australian chronically-ill adults: patient and practice characteristics matter

    Get PDF
    BackgroundTo study health-related quality of life (HRQOL) in a large sample of Australian chronically-ill patients and investigate the impact of characteristics of patients and their general practices on their HRQOL and to assess the construct validity of SF-12 in Australia.MethodsCross sectional study with 96 general practices and 7606 chronically-ill patients aged 18 years or more using standard SF-12 version 2. Factor analysis was used to confirm the hypothesized component structure of the SF-12 items. SF-12 physical component score (PCS-12) and mental component score (MCS-12) were derived using the standard US algorithm. Multilevel regression analysis (patients at level 1 and practices at level 2) was applied to relate PCS-12 and MCS-12 to patient and practice characteristics.ResultsThere were significant associations between lower PCS-12 or MCS-12 score and poorer general health (10.8 (regression coefficient) lower for PCS-12 and 7.3 lower for MCS-12), low socio-economic status (5.1 lower PCS-12 and 2.9 lower MCS-12 for unemployed, 0.8 lower PCS-12 and 1.7 lower MCS-12 for non-owner-occupiers, 1.0 lower PCS-12 for less well-educated) and having two or more chronic conditions (up to 2.7 lower PCS-12 and up to 1.5 lower MCS-12 than those having a single disease). Younger age was associated with lower MCS-12 (2.2 and 6.0 lower than middle age and older age respectively) but higher PCS-12 (4.7 and 7.6 higher than middle age and older age respectively). Satisfaction with quality of care (regression coefficient = 1.2) and patients who were married or cohabiting (regression coefficient = 0.6) was positively associated with MCS-12. Patients born in non-English-speaking countries were more likely to have a lower MCS-12 (1.5 lower) than those born in Australia. Employment had a stronger association with the quality of life of males than that of females. Those attending smaller practices had lower PCS-12 (1.0 lower) and MCS-12 (0.6 lower) than those attending larger practices. At the patient level (level 1) 42% and 21% of the variance respectively for PCS-12 and MCS-12 were explained by the patients and practice characteristics. At the practice level (level 2), 73% and 49% of the variance respectively for PCS-12 and MCS-12 were explained by patients and practice characteristics.ConclusionThe strong association between patient characteristics such as socio-economic status, age, and ethnicity and SF-12 physical and mental component summary scores underlines the importance of considering these factors in the management of chronically-ill patients in general practice. The SF-12 appears to be a valid measure for assessing HRQOL of Australian chronically-ill patients.Upali W. Jayasinghe, Judith Proudfoot, Christopher A. Barton, Cheryl Amoroso, Chris Holton, Gawaine Powell Davies, Justin Beilby and Mark F. Harri

    A method to determine spatial access to specialized palliative care services using GIS

    Get PDF
    Background: Providing palliative care is a growing priority for health service administratorsworldwide as the populations of many nations continue to age rapidly. In many countries, palliativecare services are presently inadequate and this problem will be exacerbated in the coming years.The provision of palliative care, moreover, has been piecemeal in many jurisdictions and there islittle distinction made at present between levels of service provision. There is a pressing need todetermine which populations do not enjoy access to specialized palliative care services in particular.Methods: Catchments around existing specialized palliative care services in the Canadian provinceof British Columbia were calculated based on real road travel time. Census block face populationcounts were linked to postal codes associated with road segments in order to determine thepercentage of the total population more than one hour road travel time from specialized palliativecare.Results: Whilst 81% of the province\u27s population resides within one hour from at least onespecialized palliative care service, spatial access varies greatly by regional health authority. Based onthe definition of specialized palliative care adopted for the study, the Northern Health Authorityhas, for instance, just two such service locations, and well over half of its population do not havereasonable spatial access to such care.Conclusion: Strategic location analysis methods must be developed and used to accurately locatefuture palliative services in order to provide spatial access to the greatest number of people, andto ensure that limited health resources are allocated wisely. Improved spatial access has thepotential to reduce travel-times for patients, for palliative care workers making home visits, and fortravelling practitioners. These methods are particularly useful for health service planners – andprovide a means to rationalize their decision-making. Moreover, they are extendable to a numberof health service allocation problems

    NADPH oxidase elevations in pyramidal neurons drive psychosocial stress-induced neuropathology

    Get PDF
    Oxidative stress is thought to be involved in the development of behavioral and histopathological alterations in animal models of psychosis. Here we investigate the causal contribution of reactive oxygen species generation by the phagocyte NADPH oxidase NOX2 to neuropathological alterations in a rat model of chronic psychosocial stress. In rats exposed to social isolation, the earliest neuropathological alterations were signs of oxidative stress and appearance of NOX2. Alterations in behavior, increase in glutamate levels and loss of parvalbumin were detectable after 4 weeks of social isolation. The expression of the NOX2 subunit p47phox was markedly increased in pyramidal neurons of isolated rats, but below detection threshold in GABAergic neurons, astrocytes and microglia. Rats with a loss of function mutation in the NOX2 subunit p47phox were protected from behavioral and neuropathological alterations induced by social isolation. To test reversibility, we applied the antioxidant/NOX inhibitor apocynin after initiation of social isolation for a time period of 3 weeks. Apocynin reversed behavioral alterations fully when applied after 4 weeks of social isolation, but only partially after 7 weeks. Our results demonstrate that social isolation induces rapid elevations of the NOX2 complex in the brain. Expression of the enzyme complex was strongest in pyramidal neurons and a loss of function mutation prevented neuropathology induced by social isolation. Finally, at least at early stages, pharmacological targeting of NOX2 activity might reverse behavioral alterations

    Promotoras as Mental Health Practitioners in Primary Care: A Multi-Method Study of an Intervention to Address Contextual Sources of Depression

    Get PDF
    We assessed the role of promotoras—briefly trained community health workers—in depression care at community health centers. The intervention focused on four contextual sources of depression in underserved, low-income communities: underemployment, inadequate housing, food insecurity, and violence. A multi-method design included quantitative and ethnographic techniques to study predictors of depression and the intervention’s impact. After a structured training program, primary care practitioners (PCPs) and promotoras collaboratively followed a clinical algorithm in which PCPs prescribed medications and/or arranged consultations by mental health professionals and promotoras addressed the contextual sources of depression. Based on an intake interview with 464 randomly recruited patients, 120 patients with depression were randomized to enhanced care plus the promotora contextual intervention, or to enhanced care alone. All four contextual problems emerged as strong predictors of depression (chi square, p < .05); logistic regression revealed housing and food insecurity as the most important predictors (odds ratios both 2.40, p < .05). Unexpected challenges arose in the intervention’s implementation, involving infrastructure at the health centers, boundaries of the promotoras’ roles, and “turf” issues with medical assistants. In the quantitative assessment, the intervention did not lead to statistically significant improvements in depression (odds ratio 4.33, confidence interval overlapping 1). Ethnographic research demonstrated a predominantly positive response to the intervention among stakeholders, including patients, promotoras, PCPs, non-professional staff workers, administrators, and community advisory board members. Due to continuing unmet mental health needs, we favor further assessment of innovative roles for community health workers

    Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism

    Get PDF
    YesCognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive deficits of relevance to schizophrenia in rodents and their subsequent reversal by first- and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-Choice Serial Reaction Time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of cognitive deficits and negative symptoms in schizophrenia

    Postpartum psychosis in bipolar disorder: no evidence of association with personality traits, cognitive style or affective temperaments

    Get PDF
    Background: Bipolar disorder has been associated with several personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however little research has investigated these traits and temperaments in relation to postpartum psychosis. The aim of this study is to establish whether aspects of personality, cognitive style and affective temperament that have been associated with bipolar disorder also confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. Methods: Personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments (including cyclothymic and depressive temperaments) were compared between two groups of parous women with DSM-IV bipolar I disorder: i) 284 with a lifetime history of postpartum psychosis within 6 weeks of delivery (PP group), ii) 268 without any history of mood episodes with onset during pregnancy or within 6 months of delivery (no perinatal mood episode, No PME group). Results: After controlling for current mood state, and key demographic, clinical and pregnancy-related variables, there were no statistically significant differences between the PP and No PME groups on any of the personality, cognitive style or affective temperament measures. Conclusions: Personality traits, cognitive styles and affective temperaments previously shown to be associated with bipolar disorder in general were not specifically associated with the occurrence of postpartum psychosis. These factors may not be relevant for predicting risk of postpartum psychosis in women with bipolar disorder

    D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors

    Get PDF
    Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2/), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2/. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2/. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1/), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2/. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes
    corecore