Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits.Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework.Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect).Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.

The lifetime suicide attempt rate in BD inpatients is high. Risk factors of suicide attempts were: (i) a predominant depressive course of illness, (ii) comorbid alcohol and substance use disorders, and (iii) a history of AD- and/or alcohol-induced affective episodes. Risk-reducing factors were a preponderant manic or psychotic course of the illness. These risk factors may be signs of a clinical subgroup at risk of suicidal behaviour, and seem to be important for suicide risk assessment in acutely admitted BD patients.

BackgroundAbout one in ten diagnosed with bipolar disorder (BD) has experienced a premorbid traumatic brain injury (TBI), while not fulfilling the criteria of bipolar and related disorder due to another medical condition (BD due to TBI). We investigated whether these patients have similar clinical characteristics as previously described in BD due to TBI (i.e. more aggression and irritability and an increased hypomania/mania:depression ratio) and other distinct clinical characteristics.MethodsFive hundred five patients diagnosed with BD type I, type II, or not otherwise specified, or cyclothymia were interviewed about family, medical, and psychiatric history, and assessed with the Young Mania Rating Scale (YMRS) and the Inventory of Depressive Symptoms Clinician Rated 30 (IDS-C30). Principal component analyses of YMRS and IDS-C30 were conducted. Bivariate analyses and logistic regression analyses were used to compare clinical characteristics between patients with (n = 37) and without (n = 468) premorbid TBI.ResultsPremorbid TBI was associated with a higher YMRS disruptive component score (OR 1.7, 95% CI 1.1–2.4, p = 0.0077) and more comorbid migraine (OR 4.6, 95% CI 1.9–11, p = 0.00090) independently of several possible confounders. Items on disruptive/aggressive behaviour and irritability had the highest loadings on the YMRS disruptive component. Premorbid TBI was not associated with an increased hypomania/mania:depression ratio.ConclusionsDisruptive symptoms and comorbid migraine characterize BD with premorbid TBI. Further studies should examine whether the partial phenomenological overlap with BD due to TBI could be explained by a continuum of pathophysiological effects of TBI across the diagnostic dichotomy.Trial registration ClinicalTrials.gov: NCT00201526. Registered September 2005 (retrospectively registered)Electronic supplementary materialThe online version of this article (10.1186/s40345-018-0128-6) contains supplementary material, which is available to authorized users.

ObjectiveFinseth PI, Morken G, Malt UF, Andreassen OA, Vaaler AE. Risk factors of cycle acceleration in acutely admitted patients with bipolar disorder.To identify risk factors associated with cycle acceleration (CA), that is, progressive decrease in duration of syndrome-free intervals between affective episodes, in acutely admitted patients with bipolar disorder (BD).MethodAll patients (n = 210) with BD I (67%) and BD II (33%) (DSM-IV) acutely admitted to a hospital serving a catchment area were compared in retrospect with regard to a positive or negative history of CA. Putative risk factors of CA with a P-value <0.05 in uni-variate tests were secondly entered into a logistic regression model.ResultsThe logistic regression model was statistically significant (P < 0.0001) and explained between 45.3% and 60.5% of the variance of CA status. 83.7% of the cases were correctly classified with a sensitivity of 87.2% and a specificity of 80.4%. Unique significant risk factors of CA were increasing severity of affective episodes (odds ratio (OR) = 28.8), BD II (OR = 3.3), hypomanic/manic episode induced by an antidepressant and/or alcohol (OR = 3.3), and female gender (OR = 3.1).ConclusionThe clinical factors associated with CA may help targeting patients with BD with a course aggravation, and are in line with previously reported neuropathological processes of illness progression.