Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 - 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 - 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Long-term mental health resource utilization and cost of care following group psychoeducation or unstructured group support for bipolar disorders: a cost-benefit analysis.

OBJECTIVE: To explore the short- and long-term mental health resource utilization and cost of care in a sample of 120 individuals with bipolar disorders who participated in a randomized controlled efficacy trial of group psychoeducation versus unstructured group support. METHOD: Prospective, independent monitoring of DSM-IV bipolar disorder type I or II patients aged 18 to 65 years was conducted during the intervention phase (6 months) and follow-up phase (5-year postintervention) of a randomized controlled trial reporting clinical outcomes and inpatient and outpatient mental health service utilization, with estimation of cost of treatment per patient. The study was conducted from October 1997 through October 2006. RESULTS: Compared with individuals with bipolar disorder receiving the control intervention, psychoeducated patients had twice as many planned outpatient appointments, but the estimated mean cost of emergency consultation utilization was significantly less. There were trends for psychoeducated patients to opt for self-funded psychotherapy after completing group psychoeducation and to utilize more medications. However, inpatient care accounted for 40% estimated total cost in the control group but only about 15% in the psychoeducation group. CONCLUSIONS: This study demonstrates the importance of taking a long-term overview of the cost versus benefits of adjunctive psychological therapy in bipolar disorders. If viewed only in the short-term, the psychoeducation group used more mental health care resources without clear additional health gain. However, extended follow-up demonstrated a long-term advantage for psychoeducated individuals, such that, compared to an unstructured support group intervention, group psychoeducation is less costly and more effective.

Cardiovascular risk in patients with bipolar disorder.

BACKGROUND: To date, little is known about cardiovascular risk (CVR) in terms of coronary heart disease (CHD) and cardiovascular mortality risk (CMR) in patients with bipolar disorder. This study provides data on the overall risk of any fatal or non-fatal coronary heart disease (CHD) and on the cardiovascular mortality risk (CMR) within 10 years in these patients. METHODS: Naturalistic, cross-sectional, multicenter study conducted in Spain. Patients were evaluated for cardiovascular risk using the Framinghan function (CHD) and the Systematic COronary Risk Evaluation (SCORE) function (CMR). RESULTS: The mean age was 46.6 years and 49% were male. Forty-six percent were in remission. Ten-year CHD risk was 7.6% (males 10.2% versus females 4.7%, p<0.001) and 10-year CMR was 1.8% (males 2.2% versus females 1.3%, p 0.161). Fifty-one percent smoked and 34% was obese. Metabolic syndrome was present in 22.4% of the sample (35.6% according to AHA and NHLBI criteria). Cardiovascular risk significantly increases with age, body mass index and presence of metabolic syndrome. LIMITATIONS: The cross-sectional design of the study. CONCLUSIONS: Cardiovascular risk is high in patients with bipolar disorder. It is associated with age, body mass index and metabolic syndrome. Psychiatrists should be aware of this issue and carefully monitor these patients for cardiovascular risk factors, including cigarette smoking, as part of the standard of care when treating them.