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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.

BackgroundBipolar disorder is an often recurrent mood disorder that is associated with a significant economic and health-related burden. Increasing the availability of health-economic evidence may aid in reducing this burden. The aim of this study is to describe the design of an open-source health-economic Markov model for assessing the cost-effectiveness of interventions in the treatment of Bipolar Disorders type I and II, TiBipoMod.MethodsTiBipoMod is a decision-analytic Markov model that allows for user-defined incorporation of both pharmacological and non-pharmacological interventions for the treatment of BD. TiBipoMod includes the health states remission, depression, (hypo)mania and death. Costs and effects are modeled over a lifetime horizon from a societal and healthcare perspective, and results are presented as the total costs, Quality-Adjusted Life Years (QALY), Life Years (LY), and incremental costs per QALYs and LYs gained.ResultsFunctionalities of TiBipoMod are demonstrated by performing a cost-utility analysis of mindfulness-based cognitive therapy (MBCT) compared to the standard of care. Treatment with MBCT resulted in an increase of 0.18 QALYs per patient, and a dominant incremental cost-effectiveness ratio per QALY gained for MBCT at a probability of being cost-effective of 71% when assuming a €50,000 willingness-to-pay threshold.ConclusionTiBipoMod can easily be adapted and used to determine the cost-effectiveness of interventions in the treatment in Bipolar Disorder type I and II, and is freely available for academic purposes upon request at the authors.

Abstract Background Psychoeducation (PE) for bipolar disorder (BD) has a first-line recommendation for the maintenance treatment phase of BD. Formats vary greatly in the number of sessions, whether offered individually or in a group, and with or without caregivers attending. Due to a large variation in formats in the Netherlands, a new program was developed and implemented in 17 outpatient clinics throughout the country. The current study investigated the feasibility of a newly developed 12-sessions PE group program for patients with BD and their caregivers in routine outpatient practice and additionally explored its effectiveness. Methods Participants in the study were 108 patients diagnosed with BD, 88 caregivers and 35 course leaders. Feasibility and acceptance of the program were investigated by measures of attendance, and evaluative questionnaires after session 12. Preliminary treatment effects were investigated by pre- and post-measures on mood symptoms, attitudes towards BD and its treatment, levels of self-management, and levels of expressed emotion. Results There was a high degree of satisfaction with the current program as reported by patients, caregivers, and course leaders. The average attendance was high and 83% of the patients and 75% of the caregivers completed the program. Analyses of treatment effects suggest positive effects on depressive symptoms and self-management in patients, and lower EE as experienced by caregivers. Conclusions This compact 12-sessions psychoeducation group program showed good feasibility and was well accepted by patients, caregivers, and course leaders. Preliminary effects on measures of self-management, expressed emotions, and depressive symptoms were promising. After its introduction it has been widely implemented in mental health institutions throughout the Netherlands.

Abstract Background In mental health care, clinical practice is often based on the best available research evidence. However, research findings are difficult to apply to clinical practice, resulting in an implementation gap. To bridge the gap between research and clinical practice, patients’ perspectives should be used in health care and research. This study aimed to understand the challenges people with bipolar disorder (BD) experience and examine what these challenges imply for health care and research needs. Methods Two qualitative studies were used, one to formulate research needs and another to formulate healthcare needs. In both studies focus group discussions were conducted with patients to explore their challenges in living with BD and associated needs, focusing on the themes diagnosis, treatment and recovery. Results Patients’ needs are clustered in ‘disorder-specific’ and ‘generic’ needs. Specific needs concern preventing late or incorrect diagnosis, support in search for individualized treatment and supporting clinical, functional, social and personal recovery. Generic needs concern health professionals, communication and the healthcare system. Conclusion Patients with BD address disorder-specific and generic healthcare and research needs. This indicates that disorder-specific treatment guidelines address only in part the needs of patients in everyday clinical practice.

Abstract Background Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities. Aims To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance. Methods A nationwide non-interventional study using psychiatrists’ and patients’ surveys. Results 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance. Conclusion In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.

Research evidence is incompletely translated into clinical practice. This study aimed to explore research needs from clinicians’ perspectives in the field of bipolar disorder and their reflections on patients’ research needs as well as to unravel the potential role of researcher-clinicians, to narrow the research practice gap. Using focus group discussions (FGDs) and interviews, research needs according to psychiatrists, psychologists, and nurses working with bipolar disorder were explored. Subsequently, we interviewed researcher-clinicians to gain insights into their views on patients’ research needs. The clinicians’ research needs were clustered as: causes, diagnosis, pharmacotherapy, nonpharmacological treatment, recovery, and care system, and overlapped with the research needs formulated by patients. Researcher-clinicians were able to translate patients’ needs into feasible research questions. Researcher-clinicians can serve as intermediaries between research and practice and can both integrate their practical experience into research and their research experience into practice.