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Objective To assess the prevalence of childhood trauma and types of trauma on mood disorders among young adults in a population-based sample. We further gathered data on family history of mood disorders to test the hypothesis that childhood trauma is a mediating factor for the association between family history of mood disorder and mood disorder in adulthood. Method This is a cross-sectional study, including young adults with bipolar disorder, major depressive disorder, and matched controls without any mood disorder. Childhood trauma was assessed using the Childhood Trauma Questionnaire ( CTQ). The Hicks and Tingley implementation was employed to assess whether trauma is a mediator of the effect of family history on diagnosis of any mood disorder. Results All types of trauma were associated with both major depression and bipolar disorder, with the exception of sexual abuse, which was only associated with bipolar disorder. Moreover, family history of psychiatric illness was also associated with mood disorder in adulthood and with childhood trauma. Using the presence of any mood disorder as the outcome, a third of the effect of having any family history of mood disorder was mediated via childhood trauma. Conclusion This investigation provides further support, in a population-based sample of young adults, of the association between childhood trauma and mood disorders, with sexual abuse being specifically linked with bipolar disorder. The hypothesis that childhood trauma would function as a partial mediator of the association between family history of mood disorder and mood disorder in adulthood was also confirmed. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. Method A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist ( CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines ( IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/ CCL11, IP-10, MCP-1), cytokine receptors ( sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. Results We found significant associations between sTNFR2, eotaxin/ CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. Conclusion Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders. [ABSTRACT FROM AUTHOR]

Objective We examined the relationship between biological rhythms and severity of depressive symptoms in subjects with bipolar disorder and the effects of biological rhythms alterations on functional impairment. Method Bipolar patients ( n = 260) and healthy controls ( n = 191) were recruited from mood disorders programs in three sites (Spain, Brazil, and Canada). Parameters of biological rhythms were measured using the Biological Rhythms Assessment in Neuropsychiatry ( BRIAN), an interviewer administered questionnaire that assesses disruptions in sleep, eating patterns, social rhythms, and general activity. Results Multivariate analyses of covariance showed significant intergroup differences after controlling for potential confounders (Pillai's F = 49.367; df = 2, P < 0.001). Depressed patients had the greatest biological rhythms disturbance, followed by patients with subsyndromal symptoms, euthymic patients, and healthy controls. Biological rhythms and HAMD scores were independent predictors of poor functioning ( F = 12.841, df = 6, P < 0.001, R2 = 0.443). Conclusion Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning. [ABSTRACT FROM AUTHOR]

Objective Immune activation in bipolar disorder ( BD) has been frequently reported. Damage-associated molecular patterns (DAMPs) are key players in the immune activation reaction. The aim of this study was to assess DAMP levels in drug-free patients with BD during acute episodes. Method Serum levels of a predetermined set of DAMPs were assessed in drug-free patients with BD ( n = 20) during an acute mood episode. We also included two control groups: healthy subjects, used as a negative control ( n = 20); and patients with sepsis, used as a positive control for severe immune activation ( n = 20). Results Multivariate analysis using generalized linear mixed model indicated that all DAMPs differed as a function of group membership after controlling for age and addressing multiplicity ( P < 0.0006 for all comparisons). Follow-up analyses showed higher levels in BD subjects of circulating cell-free (ccf) nuclear (n)DNA ( P = 0.02), HSP70 ( P = 0.03) and HSP90α ( P = 0.02) as compared to healthy subjects. Also, patients with BD showed lower levels of ccf nDNA ( P = 0.04), HSP60 ( P = 0.03), HSP70 ( P = 0.01), and HSP90α ( P = 0.002) as compared to patients with sepsis and higher levels of ccf mitochondrial DNA ( P < 0.0001). Conclusion The present findings may be linked to the inflammatory activity previously described among patients with BD and may help in the development of more targeted and personalized treatments for patients under acute episodes of BD. [ABSTRACT FROM AUTHOR]

Objective The impact of childhood trauma ( CT) on brain-derived neurotrophic factor ( BDNF) and cytokines levels remains unclear. We investigated the association between CT and changes in BDNF and cytokines plasma levels in children. Method We recruited 36 children with trauma ( CT+) and 26 children without trauma ( CT-). The presence of CT was based on a clinical interview and by Criteria A of DSM- IV criteria for PTSD. Blood samples were drawn from all children to assess BDNF and cytokines. ancova was performed with psychiatric symptoms and BMI as covariates to evaluate group differences in plasma levels. Results CT+ showed increased levels of BDNF and TNF-α after excluding children with history of inflammatory disease ( P < 0.05) when compared with those CT-. IL-12p70, IL-6, IL-8, IL-10, and IL-1β levels were not statistically different between groups. Conclusion CT+ showed increased BDNF and proinflammatory cytokines levels. The increase in BDNF levels may be an attempt to neutralize the negative effects of CT, while an increase in TNF-a levels be associated with a proinflammatory state after CT. How these changes associated with trauma relate to other biological changes and illness trajectory later in life remain to be further studied. [ABSTRACT FROM AUTHOR]

Objective: We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined. Method: We reviewed the literature pertaining to bipolar disorders, focusing on the first episode onwards. We systematically searched data on staging models for bipolar disorders and allied studies that could inform the concept of staging. Results: We report on several dimensions that are relevant to staging concepts in bipolar disorder. We consider whether staging offers a refinement to current diagnoses by reviewing clinical studies of treatment and functioning and the potential utility of neurocognitive, neuroimaging and peripheral biomarkers. Conclusion: Most studies to date indicate that globally defined late-stage patients have a worse overall prognosis and poorer response to standard treatment, consistent with patterns for end-stage medical disorders. We believe it is possible at this juncture to speak broadly of 'early'- and 'late'-stage bipolar disorder. Next steps require further collaborative efforts to consider the details of preillness onset and intermediary stages, and how many additional stages are optimal. [ABSTRACT FROM AUTHOR]

BACKGROUND: There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder. METHODS: We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale. RESULTS: We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups. LIMITATIONS: Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world. CONCLUSION: Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder. [ABSTRACT FROM AUTHOR]

Objective: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder. Method: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles. Results: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper. Conclusion: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson's disease, administration of high-dose dopamine precursors can produce a 'maniform' picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development. [ABSTRACT FROM AUTHOR]

A letter to the editor on mood episodes in bipolar disorder is presented.

A letter to the editor is presented in response to the article on dopamine and bipolar disorder that was published in the previous issue.