Mood disorders and prospective suicidality in young adults: a population-based cohort study.

OBJECTIVE: To assess the prospective associations of mood disorders and suicidality in a community sample of young adults from south Brazil. METHOD: Prospective population-based cohort study. Young adults (18-24 years old) were recruited and followed up on 5 years later; people were interviewed at their homes. Suicidality, as well as mood and anxiety disorders, was assessed using the Mini-International Neuropsychiatric Interview. The impact of mood episodes on suicidality was both evaluated when they occurred in the same wave (a current episode) and when suicidality occurred prospectively, with suicidality measured at follow-up (a past episode). RESULTS: The sample included 1560 young adults at baseline, with 1244 reassessed at follow-up (80.6%). Depressive episodes, both current and past, had a significant impact on suicidality in the final multivariable model. Manic episodes, however, were less consistently associated with suicidality. CONCLUSION: Depressive episodes have a strong, independent, and robust association with prospective suicidality. The association between manic episodes and suicidality, on the other hand, was dependent on the analysis and deserves further exploration.

Childhood trauma, family history, and their association with mood disorders in early adulthood.

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.

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force Report.

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.

Val66Met polymorphism and serum brain-derived neurotrophic factor in bipolar disorder: an open-label trial.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is consistently associated with acute mood episodes in bipolar disorder, but there is a lack of longitudinal data to support this hypothesis. In this 16-week open-label clinical trial, we tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and the relationship of serum BDNF and clinical response in people with bipolar disorder during an acute illness episode. METHOD: Sixty-four people with bipolar disorder who were medication-free at baseline and in an acute mood episode were recruited. They were matched with 64 healthy controls. Clinical evaluation, serum BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in serum BDNF was assessed in patients at weeks 2, 4, 8 and 16. RESULTS: There were no differences between patients and controls in serum BDNF or in frequencies of the BDNF Val66Met polymorphism genotype at baseline. The multivariable model showed that Met carriers had a significantly different change in BDNF levels compared with Val homozygotes. Not achieving a complete remission was also associated with lower prospectively assessed BDNF levels. CONCLUSION: This study provides the first longitudinal evidence that both the BDNF Val66Met polymorphism and remission status predict change in circulating BDNF levels.

Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors.

There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways.

Two studies on suicidality in the postpartum.

OBJECTIVE: Research in the prevalence of and risk factors for suicidality in the postpartum is extremely limited. We present here data on the prevalence of and factors associated with suicidality from two postpartum samples. METHOD: The first sample (SC) comprised 317 women consecutively screened for a trial of psychotherapy for postpartum depression. The second sample was a population-based (PB) sample of 386 women. We used the Mini-International Neuropsychiatric Interview (MINI) to assess suicidality in the SC sample and the self-harm question of the Beck Depression Inventory (BDI9) in the PB sample. RESULTS: According to the MINI and the BDI9, prevalence of high suicide risk was 5.7% and 11.1%, respectively, in the SC sample. Previous suicide attempts and a positive BDI were retained as predictors of suicidality. The BDI9 indicated suicidality in 8.3% of the 386 women in the PB sample; a positive BDI was retained in the multivariate analysis as a risk of suicidality. CONCLUSION: Clinicians should enquire vigorously about suicidality in women presenting with depressive symptoms or previous suicide attempts in the postpartum.

Is paternal postpartum depression associated with maternal postpartum depression? Population-based study in Brazil.

OBJECTIVE: To describe the prevalence of paternal postpartum depression (PPD) as well as its association with maternal PPD. METHOD: A population-based random sample of 386 couples was assessed from the sixth to the 12th week postpartum for demographic characteristics, alcohol misuse (AUDIT) and depressive symptoms [Beck Depression Inventory (BDI)]. Logistic regression was employed to control for potential confounders. RESULTS: In the BDI, 26.3% of mothers and 11.9% of fathers scored above the selected threshold of 10. Mild maternal depression [odds ratio (OR) 3.31, 95% CI 1.52-7.20] and moderate to severe maternal depression (OR 8.44, 95% CI 3.53-20.21) were associated with paternal PPD. CONCLUSION: Paternal PPD is a clinically meaningful phenomenon. Fathers should be evaluated for mood disorders in the postpartum, especially when their partner is depressed.