Synapsin II Is Involved in the Molecular Pathway of Lithium Treatment in Bipolar Disorder

Bipolar disorder (BD) is a debilitating psychiatric condition with a prevalence of 1–2% in the general population that is characterized by severe episodic shifts in mood ranging from depressive to manic episodes. One of the most common treatments is lithium (Li), with successful response in 30–60% of patients. Synapsin II (SYN2) is a neuronal phosphoprotein that we have previously identified as a possible candidate gene for the etiology of BD and/or response to Li treatment in a genome-wide linkage study focusing on BD patients characterized for excellent response to Li prophylaxis. In the present study we investigated the role of this gene in BD, particularly as it pertains to Li treatment. We investigated the effect of lithium treatment on the expression of SYN2 in lymphoblastoid cell lines from patients characterized as excellent Li-responders, non-responders, as well as non-psychiatric controls. Finally, we sought to determine if Li has a cell-type-specific effect on gene expression in neuronal-derived cell lines. In both in vitro models, we found SYN2 to be modulated by the presence of Li. By focusing on Li-responsive BD we have identified a potential mechanism for Li response in some patients

Suicide and suicide attempts in people with severe mental disorders in Butajira, Ethiopia:10 year follow-up of a population-based cohort

Background: People with severe mental disorders (SMD) are at higher risk of suicide. However, research into suicide attempts and completed suicide in people with SMD in low-and middle-income countries is mostly limited to patients attending psychiatric facilities where selection bias is likely to be high. Methods: A population-based cohort of 919 people with SMD from rural Ethiopia (who received standardized clinician diagnoses of schizophrenia (n = 358) major depressive disorder (n = 216) and bipolar I disorder (n = 345)) were followed up annually for an average of 10 years. The Longitudinal Interval Follow-up Evaluation chart was administered by psychiatrists and used to evaluate systematically suicidal behavior and risk factors, which may be amenable to intervention. Results: Over the follow-up period, the cumulative risk of suicide attempt was 26.3% for major depression, 23.8% for bipolar I disorder and 13.1% for schizophrenia, (p < 0.001). The overall incidence of completed suicide was 200.2/100,000 person-years (CI = 120.6, 312.5). Hanging was the most frequent method used (71.5%) for both attempters and completers. Most people who completed suicide were successful on the first attempt (84.2%), but the case-fatality rate for suicide attempt was 9.7%. In the adjusted logistic regression model, being currently married (Adjusted OR) =2.17, 95% CI = 1.21, 3.91), and having a diagnosis of bipolar I disorder (Adjusted OR = 2.59, 95% CI = 1.57, 4.26) or major depression (Adjusted OR = 2.71, 95% CI = 1.60, 4.58) were associated significantly with increased risk of suicide attempts. Conclusion: In this sample of people with SMD from a rural setting, the rate of suicide was high. Initiatives to integrate mental health service into primary care need to focus on limiting access to suicide methods in people with SMD in addition to expanding access to mental health care