Citations

ObjectivesThe aim of the present study was to engage a national advocacy group and local stakeholders for guidance in developing a bipolar disorder biobank through a web‐based survey and a community advisory board.MethodsThe Depression and Bipolar Support Alliance and the Mayo Clinic Bipolar Biobank conducted a national web‐based survey inquiring about interest in participating in a biobank (i.e., giving DNA and clinical information). A community advisory board was convened to guide establishment of the biobank and identify key deliverables from the research project and for the community.ResultsAmong 385 survey respondents, funding source (87%), professional opinion (76%), mental health consumer opinion (79%), and return of research results (91%) were believed to be important for considering study participation. Significantly more patients were willing to participate in a biobank managed by a university or clinic (78.2%) than one managed by government (63.4%) or industry (58.2%; both p < 0.001). The nine‐member community advisory board expressed interest in research to help predict the likelihood of bipolar disorder developing in a child of an affected parent and which medications to avoid. The advisory board endorsed the use of a comprehension questionnaire to evaluate participants' understanding of the study (e.g., longevity of DNA specimens, right to remove samples, accessing medical records) as a means to strengthen the informed consent process.ConclusionsThese national survey and community advisory data support the merit of establishing a biobank to enable studies of disease risk, provided that health records and research results are adequately protected. The goals of earlier diagnosis and individualized treatment of bipolar disorder were endorsed.

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.

ObjectivesThe aim of the present study was to examine N‐acetylaspartate (NAA), a general marker of neuronal viability, and total NAA (tNAA), the combined signal of NAA and N‐acetylaspartylglutamate, in bipolar depression before and after lamotrigine treatment. Given that NAA is synthesized through direct acetylation of aspartate by acetyl‐coenzyme A‐l‐aspartate‐N‐acetyltransferase, we hypothesized that treatment with lamotrigine would be associated with an increase in NAA level.MethodsPatients with bipolar depression underwent two‐dimensional proton magnetic resonance spectroscopy of the anterior cingulate at baseline (n = 15) and after 12 weeks of lamotrigine treatment (n = 10). A group of age‐matched healthy controls (n = 9) underwent scanning at baseline for comparison.ResultsAt baseline, patients with bipolar depression had significantly lower NAA [mean standard deviation (SD) = 1.13 (0.21); p = 0.02] than controls [mean (SD) = 1.37 (0.27)]. Significant increases in NAA [mean (SD) = 1.39 (0.21); p = 0.01] and tNAA [mean (SD) = 1.61 (0.25); p = 0.02] levels were found after 12 weeks of lamotrigine treatment.ConclusionsThese data suggest an NAA deficit in bipolar depression that is normalized after lamotrigine treatment. Future research is warranted to evaluate whether baseline NAA level is a potential biomarker for identifying lamotrigine response patterns and whether this functional brain change has an associated clinical response.

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.

ObjectiveEarly‐onset bipolar (BP) disorder and other poor prognosis characteristics are more prevalent in patients from the United States than from the Netherlands and Germany (abbreviated as Europe). We explored the impact of parental loading for affective illness on onset and other characteristics of BP disorder.MethodParental history for unipolar (UP) and bipolar (BP) depression and course of illness characteristics were obtained from self‐report in adults (average age 42) with BP disorder. Illness characteristics were examined by χ2 and multinomial logistic regression in relationship to the degree of parental loading: i) both parents negative; ii) one UP disorder; iii) one with BP disorder; and iv) both affected.ResultsAfter controlling for many poor prognosis factors, compared with those from Europe, patients from the United States had more iii) one parent with BP disorder and iv) both parents affected. An early age of onset of BP disorder was independently associated with this increased parental loading for affective disorder.ConclusionParental history of BP disorder and both parents with a mood disorder were more common in the United States than Europe and were associated with an early onset of bipolar disorder and other poor prognosis characteristics. These findings deserve replication and exploration of the potential mechanisms involved and their therapeutic implications.

IntroductionUnderstanding the course and determinants of sleep disturbances in alcoholic patients may help identify patients at high risk of persistent sleep problems, relapse and guide treatment interventions.MethodsWe prospectively administered the Pittsburgh Sleep Quality Index (PSQI) to all patients (N = 196) admitted to a 1‐month residential treatment program. Our analysis excluded patients with active drug abuse/dependence. Demographic data, psychiatric diagnoses, Patient Health Questionnaire‐9 (PHQ‐9), Alcohol Use Disorders Identification Test (AUDIT) and Inventory of Drug Taking Situations (IDTS) scores were obtained. Univariate and logistic regression analyses were performed using sex, age, hazardous alcohol use, PHQ‐9 scores, hypnotic use, and use of alcohol as a hypnotic as correlates to admission PSQI scores and improvement in PSQI scores.ResultsA total of 119 alcoholic patients met inclusion criteria (mean age 50.6 ± 13.2 years). The rates of sleep disturbances at admission and discharge were 69.3% and 49.1%, respectively. Self report of using alcohol to fall asleep and use of hypnotics were associated with elevated PSQI scores. Total PSQI scores improved over 4 weeks (p < .001). Change in PSQI scores was not effected by gender, use of hypnotics, hazardous alcohol use, use of alcohol as a hypnotic or co‐morbid psychiatric diagnosis. Older age predicted improvement in PSQI scores in patients with sleep disturbances (p = .004).ConclusionWhile a large proportion of alcoholics had sleep disturbances upon admission and at discharge from a residential treatment program, only older age was associated with improvements in sleep disturbances during early alcohol recovery. (Am J Addict 2014;23:21–26)

Background and ObjectivesThe aim of this study was to investigate potential gender differences in situations associated with heavy alcohol drinking.MethodsData from 395 alcohol dependent patients participating in the Mayo Clinic Intensive Addiction Program were evaluated. Each participant completed the inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS), patient health questionnaire (PHQ‐9), and/or Beck depression inventory (BDI). Gender differences in IDTS scores representing three domains (negative, positive, and temptation) of situations associated with heavy alcohol use were examined.ResultsWomen with alcohol dependence report a higher frequency of heavy drinking in unpleasant emotional (IDTS negative scores mean ± SD women vs. men: 52.3 ± 22.1 vs. 43.8 ± 21.8; p = .0006), and as a result of temptation (IDTS temptation scores mean ± SD women vs. men: 40.4 ± 23.0 vs. 35.3 ± 20.8; p = .035). Upon admission, women also scored significantly higher on depressive symptoms as measured by the BDI (23.4 ± 11.4 vs. 18.2 ± 9.8, p < .001). After controlling for depressive symptom severity as a covariate, the IDTS gender differences were no longer significant.Conclusion and Scientific SignificanceOur results suggest that unpleasant or temptation based emotional situations are a vulnerability risk factor for heavy drinking particularly in females. This risk appears to be at least partially driven by depressive symptom burden. Future research is needed to further investigate this finding. (Am J Addict 2013;22:437–442)

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.