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Vargas H.O.,State University Londrina | Nunes S..O.V.,State University Londrina | Bortolasci C.C.,State University Londrina | Barbosa D.S.,State University Londrina | And 10 more authors.
Journal of Affective Disorders | Year: 2013

Background: There is evidence that depression is accompanied by inflammation, oxidative and nitrosative stress (O&NS) and metabolic disorders. However links between oxidative stress and suicide attempts in depressed patients are poorly understood. This study examines whether a history of suicide attempts is associated with inflammation, O&NS and metabolic disorders. Methods: Blood specimens were collected from study participants aged 18-60 (N=342) recruited at the State University of Londrina, Brazil, and measured for oxidative stress biomarkers: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde, advanced oxidation protein products and plasma total antioxidant potential (TRAP); inflammatory biomarkers: fibrinogen, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, interleukin-6 and tumor necrosis factor-a; and metabolic variables. Subjects were divided into those with (n = 141) and without (n=201) a history of suicidal attempts. Results: Individuals with a history of suicide attempts had significantly higher levels of NOx and lipid hydroperoxides and lowered TRAP as compared to individuals without suicide attempts. There were no significant associations between a history of suicide attempts and inflammatory and metabolic biomarkers and metabolic syndrome. Logistic regression showed that both unipolar and bipolar disorder, female gender, smoking behavior and lipid hydroperoxides were significantly associated with a history of suicide attempts. The combined effects of oxidative stress, smoking, depression, female gender were independent from classical risk factors, including marital status, years of education and anxiety. Conclusions: O&NS as well as lowered antioxidant levels may play a role in the pathophysiology of suicidal behavior independently from the effects of depression and smoking, both of which are associated with increased O&NS, and classical suicide predictors, such as years of education and marital status. © 2013 Elsevier B.V. All rights reserved.


Dodd S.,University of Melbourne | Brnabic A.J.M.,Eli Lilly and Company | Berk L.,University of Melbourne | Berk L.,Orygen Research Center | And 13 more authors.
Comprehensive Psychiatry | Year: 2010

Background: Tobacco smoking is more prevalent among people with mental illnesses, including bipolar disorder, than in the general community. Most data are cross-sectional, and there are no prospective trials examining the relationship of smoking to outcome in bipolar disorder. The impact of tobacco smoking on mental health outcomes was investigated in a 24-month, naturalistic, longitudinal study of 240 people with bipolar disorder or schizoaffective disorder. Method: Participants were interviewed and data recorded by trained study clinicians at 9 interviews during the study period. Results: Comparisons were made between participants who smoked daily (n = 122) and the remaining study participants (n = 117). During the 24-month study period, the daily smokers had poorer scores on the Clinical Global Impressions-Depression (P = .034) and Clinical Global Impressions-Overall Bipolar (P = .026) scales and had lengthier stays in hospital (P = .012), compared with nonsmokers. Limitations: Smoking status was determined by self-report. Nicotine dependence was not measured. Conclusion: These findings suggest that smoking is associated with poorer mental health outcomes in bipolar and schizoaffective disorder. © 2010 Elsevier Inc. All rights reserved.


Berk M.,Deakin University | Berk M.,University of Melbourne | Berk M.,Swanston Center | Berk M.,The Mental Health Research Institute of Victoria | And 12 more authors.
Bipolar Disorders | Year: 2011

Objective: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention. Methods: Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1-5, 6-10, or >10 prior episodes of illness, and data were analyzed across these groups. Results: Response rates for the mania and maintenance studies ranged from 52-69% and 10-50%, respectively, for individuals with 1-5 previous episodes, and from 29-59% and 11-40% for individuals with >5 previous episodes. These rates were significantly higher for the 1-5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1-5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40-60% for those who had experienced 1-5 episodes or 6-10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1-5 episode group (p=0.005). Conclusion: Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention. © 2011 John Wiley and Sons A/S.


Odebrecht Vargas Nunes S.,State University Londrina | Pizzo De Castro M.R.,State University Londrina | Ehara Watanabe M.A.,State University Londrina | Losi Guembarovski R.,State University Londrina | And 9 more authors.
Psychiatric Genetics | Year: 2014

BACKGROUND: Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. MATERIALS AND METHODS: Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. RESULTS: Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05-4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24-9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95-23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23-129.91, P<0.006). CONCLUSION: This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress.©2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Malhi G.S.,Royal North Shore Hospital | Malhi G.S.,University of Sydney | Bargh D.M.,Royal North Shore Hospital | Bargh D.M.,University of Sydney | And 9 more authors.
Bipolar Disorders | Year: 2012

Objective: To provide practical and clinically meaningful treatment recommendations that amalgamate clinical experience and research findings for each phase of bipolar disorder. Methods: A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Cochrane reviews) using key words (e.g., bipolar depression, mania, treatment). All relevant randomised controlled trials were examined, along with review papers, meta-analyses, and book chapters known to the authors. In addition, the recommendations from accompanying papers in this supplement have been distilled and captured in the form of summary boxes. The findings, in conjunction with the clinical experience of international researchers and clinicians who are practiced in treating mood disorders, formed the basis of the treatment recommendations within this paper. Results: Balancing clinical experience with evidence informed and lead to the development of practical clinical recommendations that emphasise the importance of safety and tolerability alongside efficacy in the clinical management of bipolar disorder. Conclusions: The current paper summarises the treatment recommendations relating to each phase of bipolar disorder while providing additional, evidence-based, practical insights. Medication-related side effects and monitoring strategies highlight the importance of safety and tolerability considerations, which, along with efficacy information, should be given equal merit. © 2012 John Wiley and Sons A/S.


Singh A.B.,Deakin University | Nierenberg A.A.,Deakin University | Nierenberg A.A.,Harvard University | Yatham L.N.,University of British Columbia | And 4 more authors.
BMC Medicine | Year: 2014

With escalating health expenditure and a shrinking purse, there is increased focus on the cost efficacy of still patented versus generic medications in general, and for atypical antipsychotics in particular. In a recent BMC Medicine article, Godman and colleagues presented data indicating poor uptake of the off patent atypical antipsychotic risperidone, arguing for authorities to mandate its greater use. This is under the assumption of clinical equivalence of atypical antipsychotics. This commentary argues that there are clinically meaningful differences between atypical antipsychotics and important inter-individual heterogeneity in clinical response and tolerability. Access to a broad range of atypical antipsychotics enables clinicians to tailor care, taking consideration of differential efficacy and adverse effects profile in order to meet the needs of individual patients with improved real world effectiveness of treatment. Restriction of agent choice risks detracting from optimal clinical care, with possible poorer outcomes and greater costs of care. A balance between encouraging use of cheapest in class agent and allowing access to various atypical agents for tailored care is likely to produce optimal health outcomes.Please see related article: http://www.biomedcentral.com/1741-7015/12/98. © 2014 Singh et al.


Daglas R.,University of Melbourne | Conus P.,University of Lausanne | Cotton S.M.,University of Melbourne | Macneil C.A.,Orygen Youth Health Clinical Program | And 5 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2014

Objective: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania.Methods: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point.Results: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect.Conclusions: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated. © 2014 The Royal Australian and New Zealand College of Psychiatrists.


Malhi G.S.,Royal North Shore Hospital | Malhi G.S.,University of Sydney | Tanious M.,Royal North Shore Hospital | Tanious M.,University of Sydney | And 7 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2012

Introduction: Despite more that 60 years of clinical experience, the effective use of lithium for the treatment of mood disorder, in particular bipolarity, is in danger of becoming obsolete. In part, this is because of exaggerated fears surrounding lithium toxicity, acute and long-term tolerability and the encumbrance of life-long plasma monitoring. Recent research has once again positioned lithium centre stage and amplified the importance of understanding its science and how this translates to clinical practice.Objective: The aim of this paper is to provide a sound knowledge base as regards the science and practice of lithium therapy.Method: A comprehensive literature search using electronic databases was conducted along with a detailed review of articles known to the authors pertaining to the use of lithium. Studies were limited to English publications and those dealing with the management of psychiatric disorders in humans. The literature was synthesized and organized according to relevance to clinical practice and understanding.Results: Lithium has simple pharmacokinetics that require regular dosing and monitoring. Its mechanisms of action are complex and its effects are multi-faceted, extending beyond mood stability to neuroprotective and anti-suicidal properties. Its use in bipolar disorder is under-appreciated, particularly as it has the best evidence for prophylaxis, qualifying it perhaps as the only true mood stabilizer currently available. In practice, its risks and tolerability are exaggerated and can be readily minimized with knowledge of its clinical profile and judicious application.Conclusion: Lithium is a safe and effective agent that should, whenever indicated, be used first-line for the treatment of bipolar disorder. A better understanding of its science alongside strategic management of its plasma levels will ensure both wider utility and improved outcomes. © The Royal Australian and New Zealand College of Psychiatrists 2012.


Berk L.,Orygen Youth Health Research Center | Berk L.,University of Melbourne | Berk L.,Swanston Center | Jorm A.F.,Orygen Youth Health Research Center | And 9 more authors.
Bipolar Disorders | Year: 2011

Objectives: Close family and friends are often a primary source of support for a person with bipolar disorder. However, there is a lack of information for caregivers about ways to provide helpful support and take care of themselves. Rates of caregiver burden are high and increase the risk of caregiver depression and health problems. This study aimed to develop guidelines to assist caregivers of adults with bipolar disorder to be informed about bipolar disorder and to support the person without neglecting their own wellbeing. Methods: The Delphi method was used to assess consensus between international expert panels of 45 caregivers, 47 consumers, and 51 clinicians about what information to include in the caregiver guidelines. Initial online survey items were based on the existing literature. Subsequent surveys included new or reworded items suggested by panel members and items that needed re-rating. Items endorsed by at least 80% of all three panels formed the content of the guidelines. Results: Nearly 86% of the 626 survey items were endorsed. The items covered information on the illness, treatment, and suggestions on ways caregivers can provide support and take care of themselves in the different phases of illness and wellness, and information on dealing with specific real-life challenges. Although consensus rates were high, meaningful areas of difference between panels were found (e.g., collaboration issues). Conclusions: The guidelines provide comprehensive introductory information, suggestions, and resources for caregivers. Access to relevant information may help caregivers to cope constructively with the person's bipolar disorder and their caregiving situation. The content of the guidelines could be used to help formulate a stepped-care approach to supporting caregivers, ranging from basic information and pamphlets to brief training courses and specialized family or caregiver interventions based on need and accessibility. © 2011 John Wiley and Sons A/S.


Berk L.,Deakin University | Berk L.,University of Melbourne | Berk L.,Swanston Center | Berk M.,Deakin University | And 11 more authors.
BMC Medicine | Year: 2013

Background: Bipolar disorder is associated with extreme mood symptoms, disability and suicide risk. Close family or friends often have a primary role in supporting an adult with bipolar disorder. However, not all support is helpful and there is little publicly accessible evidence-based information to guide caregivers. Caregiver burden increases the risk of caregiver depression and health problems. To help fill the information gap, expert clinicians, caregivers and consumers contributed to the development of guidelines for caregivers of adults with bipolar disorder using the Delphi consensus method. This paper reports on an evaluation of the acceptability and usefulness of the online version of the guidelines, http://www.bipolarcaregivers.org.Methods: Visitors to the website responded to an initial online survey about the usefulness of the information (N = 536). A more detailed follow-up feedback survey was emailed to web users who were adult caregivers of adults with bipolar disorder a month later (N = 121). The feedback was analyzed quantitatively and qualitatively to establish user appraisals of the online information, whether and how caregivers applied the information and ways it could be improved.Results: The majority of users (86.4% to 97.4%) found the various sections of the website useful. At follow-up, nearly 93% of caregivers reported that the information was relevant to them and 96% thought it would help others. Most respondents said that the information was supportive and encouraged adaptive control appraisals. However, a few respondents who were experiencing complex family problems, or who cared for a person with severe chronic bipolar disorder did not appraise it as positively. Nevertheless, over two-thirds of the caregivers reported using the information. Optional interactive features were recommended to maximize benefits.Conclusions: Overall, http://www.bipolarcaregivers.org was appraised positively and used. It appears useful to close family and friends seeking basic information and reassurance, and may be an inexpensive way to disseminate guidelines for caregivers. Those who care for people with more severe and chronic bipolar disorder, or who have complex family problems might benefit from more specialized interventions, suggesting the importance of a stepped-care approach to supporting caregivers. The potential of evidence-based, collaboratively developed information websites to enhance caregiver and consumer outcomes merits further investigation. © 2013 Berk et al.; licensee BioMed Central Ltd.

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