Cuéllar‐Barboza, Alfredo B.

ObjectivesTo examine the independent effects of sex on the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I disorder (BP‐I) or bipolar II disorder (BP‐II).MethodsWe analyzed data from the first 1,225 patients enrolled in the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. Demographic and clinical variables were ascertained using standardized questionnaires; height and weight were assessed to determine body mass index (BMI). Rates of rapid cycling, cycle acceleration, and increased severity of mood episodes over time were compared between women and men overall and within subgroups defined by bipolar disorder subtype (BP‐I or BP‐II). Multiple logistic regression analysis was used to assess the independent effect of sex on the risk of these indicators of adverse illness course.ResultsWomen had significantly higher rates of rapid cycling than men. Overall rates of rapid cycling were higher in patients with BP‐II than BP‐I; and sex differences in the rate of rapid cycling were more pronounced in patients with BP‐II than BP‐I, although the power to detect statistically significant differences was reduced due to the lower sample size of subjects with BP‐II. Female sex was a significant predictor of rapid cycling, cycle acceleration, and increased severity of mood episodes over time after adjusting for age, bipolar disorder subtype, BMI, having any comorbid psychiatric disorder, and current antidepressant use.ConclusionsFemale sex was associated with significantly higher risk of rapid cycling, cycle acceleration, and increased severity of mood episodes over time in a sample of 1,225 patients with bipolar disorders.

ObjectivesBrain‐derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early‐onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association.MethodsDNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early‐onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult‐onset cases at age >19 years). After quality control, 69 TEAM early‐onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early‐onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log‐additive allele effects.ResultsComparison of TEAM cases with controls suggested association of early‐onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early‐onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early‐onset TEAM and Mayo Clinic early‐onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04).ConclusionsThese preliminary analyses of a relatively small sample with early‐onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early‐onset expression of the disorder.

ObjectivesTo determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder.MethodsThis cross‐sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM‐IV‐TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13‐item organ‐based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature.ResultsIn a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66–5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69–3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03–2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67–6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61–3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96–2.13, p = 0.08).ConclusionsThe phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association.

ObjectiveTo review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder.MethodA systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 – May, 2013) was conducted. Case‐control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random‐effects meta‐analysis.ResultsFive cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta‐analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96–1.24, P = 0.20; I2 = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29–2.35; P = 0.0003; I2 = 83%).ConclusionThere may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features.