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Magalhaes P.V.,National Institute for Translational Medicine | Magalhaes P.V.,University of Melbourne | Dean O.M.,University of Melbourne | Dean O.M.,Mental Health Research Institute of Victoria | And 11 more authors.
Journal of Affective Disorders | Year: 2011

Background: The evidence base for the pharmacological treatment of bipolar II disorder is limited. In bipolar disorder, there is evidence for glutathione depletion and increased oxidative stress, as well as dysregulation of glutamate; N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. In this report, we explore the effects of this compound in a subset of patients with bipolar II disorder from that trial. Methods: Individuals were randomized to NAC or placebo in addition to treatment as usual, in a double-blind fashion. Mood and functional outcomes were assessed up to 24 weeks of treatment. Results: Fourteen individuals were available for this report, seven in each group. Six people achieved full remission of both depressive and manic symptoms in the NAC group; this was true for only two people in the placebo group (χ2 = 4.67, p = 0.031). Limitations: Subgroup analyses in a small subsample of patients. Not all participants had elevated depression scores at baseline. Conclusion: Notwithstanding all the limitations that subgroup analysis of trials carry, this data could serve as a hypothesis-generating stimulus for further clinical trials of pharmacologic treatment for bipolar II depression. © 2010 Elsevier B.V. All rights reserved.

Jansen K.,Catholic University of Pelotas | Magalhaes P.V.S.,National Institute for Translational Medicine | Tavares Pinheiro R.,Catholic University of Pelotas | Kapczinski F.,National Institute for Translational Medicine | Silva R.A.D.,Catholic University of Pelotas
Journal of Affective Disorders | Year: 2012

Objectives: The objective of this report is to evaluate functioning in bipolar disorder in a population-based sample of young adults (18 to 24 years old). To this end, people with bipolar disorder were compared with matched participants with only depressive episodes and control subjects without a history of mood episodes. Methods: Case-control study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. The Functioning Assessment Short Test was used as a measure of general functioning. A multivariate model was elaborated to account for potential confounders. Results: The sample consisted of 231 subjects. Both bipolar disorder (coef=0.60, SE=0.14, p<0.001) and major depression (coef=0.44, SE=0.14, p=0.001) were associated with functioning in the multivariate model. Current depressive symptoms appeared to influence functioning in those with major depression (Z=2.05, p=0.04), but not in those with bipolar disorder (Z=0.78, p=0.43). Limitation: Neuropsychological testing was not performed and we see it as an important limitation of this study. Conclusion: This population-based study further reinforces the notion that functional impairment is a fundamental characteristic of bipolar illness. It is present from early stages and is not completely explained by mood symptoms. © 2012 Elsevier B.V.

Brietzke E.,University of Sao Paulo | Moreira C.L.R.L.,University of Sao Paulo | Duarte S.V.B.,University of Sao Paulo | Nery F.G.,University of Sao Paulo | And 4 more authors.
Comprehensive Psychiatry | Year: 2012

Background: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. Objective: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. Methods: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined bipolar I or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. Results: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. Conclusions: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses. © 2012 Elsevier Inc.

Brietzke E.,University of Sao Paulo | Mansur R.B.,University of Sao Paulo | Soczynska J.K.,University of Toronto | Kapczinski F.,Federal University of Rio Grande do Sul | And 3 more authors.
Journal of Affective Disorders | Year: 2012

Background: The high prevalence, recurrence rate, chronicity, and illness burden in bipolar disorder (BD) are well documented. Moreover, insufficient response with conventional pharmacological and manual-based psychosocial interventions, as well as evidence of illness progression and acceleration, invite the need for early detection and primary prevention. Methods: Herein we comprehensively review extant studies reporting on a bipolar prodrome. The overarching aim is to propose a predictive algorithm (i.e. prediction of BD in at-risk populations) integrating genetic (i.e. family history), environmental (e.g. childhood maltreatment) and biological markers (i.e. BDNF, inflammatory and oxidative stress markers). Computerized databases i.e. Pubmed, PsychInfo, Cochrane Library and Scielo were searched using the followed terms: bipolar disorder cross-referenced with prodromal, preclinical, at risk mental states, clinical high risk, ultra high risk, biomarkers, brain-derived neurotrophic factor, inflammation, cytokines, oxidative stress, prediction and predictive model. Results: Available evidence indicates that a prodrome to bipolar disorder exists. Commonly encountered features preceding the onset of a manic episode are affective lability, irritability, anger, depression, anxiety, substance use disorders, sleep disorders, as well as disturbances in attention and cognition. Non-specificity and insufficient sensitivity have hampered the development of an adequate prediction algorithm. Limitations: Limitations include biases associated with retrospective studies, poor characterization of clinical high risk, inadequacy of prospective studies regarding sample selection and absence of specificity of risk states. Conclusion: We propose a hypothetical prediction algorithm that is combinatorial in approach that attempts to integrate family history, early adversity, and selected biomarkers. © 2012 Elsevier B.V.

Freire R.C.,Federal University of Rio de Janeiro | Freire R.C.,National Institute for Translational Medicine | Perna G.,San Benedetto Hospital | Nardi A.E.,Federal University of Rio de Janeiro | Nardi A.E.,National Institute for Translational Medicine
Harvard Review of Psychiatry | Year: 2010

Objective: Our objective is to summarize the new findings concerning the respiratory subtype (RS) of panic disorder (PD) since its first description. Methods: Two searches were made in the Institute for Scientific Information Web of Science: with the keywords "panic disorder" and "respiratory symptoms," and all articles that cited Briggs and colleagues' 1993 article "Subtyping of Panic Disorder by Symptom Profile" (Br J Psychiatry 1993;163:2019). Altogether, 133 articles were reviewed. Results: We describe and discuss RS epidemiology, genetics, psychopathology, demographic features, clinical features, correlations with the respiratory system, traumatic suffocation history, provocative tests, and nocturnal panic. Compared to patients with the nonrespiratory subtype (non-RS), the RS patients had higher familial history of PD, lower comorbidity with depression, longer duration of illness, lower neuroticism scores, and higher scores in severity scales, such as the Panic and Agoraphobia Scale, Panic-Agoraphobia Spectrum scale and the Clinical Global Impression scale. Tests to induce panic attacks, such as those with CO2, hyperventilation, and caffeine, produce panic attacks in a higher proportion of RS patients than non-RS patients. Differences in the subtypes' improvement with the pharmacologic treatment were found. There are also some controversial findings regarding the RS, including the age of onset of PD, and alcohol and tobacco use in RS patients. Conclusions: Some characteristics, such as the increased sensitivity to CO2 and the higher familial history of PD, clearly distinguish the RS from the non-RS. Nevertheless, there are also controversial findings. More studies are needed to determine the validity of the RS subtype. © 2010 President and Fellows of Harvard College.

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