Byungsu Kim

Bipolar disorder and metabolic syndrome: an international perspective.

INTRODUCTION The ubiquity and hazards posed by abnormal body composition and metabolic parameters in the bipolar population are a priority research and clinical issue. Herein, we summarize and synthesize international studies describing the rate of US National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III])- and International Diabetes Federation (IDF)-defined metabolic syndrome and its criterion components in individuals with bipolar disorder. METHODS We conducted a PubMed search of all English-language articles published between January 2005 and July 2009 with the following search terms: metabolic syndrome and bipolar disorder, mania and manic-depression. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. RESULTS The rate of metabolic syndrome in individuals with bipolar disorder is increased relative to the general population. Disparate estimates are reported ranging from comparability to approximately twofold greater than the general population. The increased hazard for metabolic syndrome amongst bipolar individuals is now documented in twelve countries from Europe, Australia, Asia, North and South America. The co-occurrence of metabolic syndrome in the bipolar population is associated with a more complex illness presentation, less favourable response to treatment, and adverse course and outcome. The association between metabolic syndrome and bipolar disorder is mediated/moderated by both iatrogenic and non-iatrogenic factors. DISCUSSION The increased hazard for metabolic syndrome in bipolar populations is due to the clustering of traditional (and emerging) risk factors as well as iatrogenic and health systems factors. Extant data support recommendations for prioritizing, surveillance, prevention, diagnosis and management of metabolic syndrome as routine care of the bipolar patient.

Association of the Glutamate Transporter Gene SLC1A1 With Atypical Antipsychotics-Induced Obsessive-compulsive Symptoms

CONTEXT Several studies have indicated that atypical antipsychotics (AAP) induce obsessive-compulsive (OC) symptoms. Research exploring the mechanism of this phenomenon, however, has been extremely limited. Considering the indirect evidence of genetic control and difficulties in developing animal models and performing gene expression studies, genetic association studies could be an important approach to understanding the molecular mechanism of AAP-induced OC symptoms. The glutamate transporter gene SLC1A1, which was recently reported to be associated with obsessive-compulsive disorder (OCD), is a promising candidate gene for susceptibility to AAP-induced OC symptoms. OBJECTIVE To determine whether polymorphisms in SLC1A1 are associated with AAP-induced OC symptoms in patients with schizophrenia. DESIGN A pharmacogenetic case-control association study. SETTING Outpatient schizophrenia clinics. PATIENTS Clinically stable patients with schizophrenia who were receiving AAP treatment (n = 94; OC group). The OC group consisted of 40 patients with AAP-induced OC symptoms, and the non-OC group consisted of 54 patients who had received AAP for more than 24 months without developing OC symptoms. MAIN OUTCOME MEASURES Allele, genotype, and haplotype frequencies. The association was tested with a logistic regression model using age, sex, and medication type as covariates. RESULTS Trends of association were observed in rs2228622 and rs3780412 (nominal P = .01; adjusted permutation P = .07) for the dominant model that was the inheritance model that best fit our data. In the haplotype -based analysis, the A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with AAP-induced OC symptoms; this association withstood multiple test correction (nominal P = .01; adjusted permutation P = .04; odds ratio, 3.955; 95% confidence interval, 1.366-11.452, for dominant model). CONCLUSIONS These results suggest that sequence variations in SLC1A1 are associated with susceptibility to AAP-induced OC symptoms. This is the first published pharmacogenetic study on this phenomenon and provides preliminary evidence of the involvement of glutamatergic neurotransmission in the pathogenesis of AAP-induced OC symptoms.

Brain-derived neurotrophic factor Val/Met polymorphism and bipolar disorder. Association of the Met allele with suicidal behavior of bipolar patients.

Background/Aims: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. Methods: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. Results: Allelic distributions did not differ significantly between bipolar patients and controls (χ2 = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (χ2 = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7–14.7). Conclusions: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.

Bipolarity in depressive patients without histories of diagnosis of bipolar disorder and the use of the Mood Disorder Questionnaire for detecting bipolarity

OBJECTIVES The present study was performed to evaluate the frequency of bipolar disorders among patients (a) presenting with depressive episodes but (b) who have never been diagnosed with bipolar disorder (c) in routine clinical practice in Korean subjects and to identify which clinical features were helpful in discriminating bipolar patients from unipolar patients. In addition, authors assessed the practical use of the Mood Disorder Questionnaire (MDQ) to distinguish bipolar from unipolar disorder in these subjects and tested whether modifications of the MDQ scoring could improve its performance. METHODS We evaluated consecutive patients who satisfied the inclusion criteria of a current depressive episode, plus at least one previous depressive episode. Subjects were interviewed for diagnosis using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV after completing the MDQ. To improve assessment of hypomania history, the interviewer made strenuous efforts to explore a possible history of hypomania, and patient-derived data were supplemented by information from family members or close relatives. RESULTS Fifty-nine patients (53.2%) were classified as having bipolar disorder, leaving a group of 52 (46.8%) with unipolar depression. Among bipolar disorders, 1.8% (n = 2) had bipolar I disorder; 29.7% (n = 33), bipolar II disorder; 6.3% (n = 7), bipolar III disorder (history of antidepressant-induced hypomania without spontaneous hypomanic episode); and 15.3% (n = 17), bipolar disorder not otherwise specified (1-3 days brief hypomania). Postpartum depression (relative risk [RR] [95% confidence interval {CI}], 2.00 [1.23-3.24]), early age of onset (RR [95% CI], 1.85 [1.30-2.64]), mood lability (RR [95% CI], 1.85 [1.30-2.64]), brief depressive episode (RR [95% CI], 1.66 (1.16-2.37]), bipolar family history (RR [95% CI], 1.62 [1.08-2.43]), history of suicide attempt (RR [95% CI], 1.47 (1.05-2.04]), and alcohol problem (RR [95% CI], 1.45 (1.04-2.02]) were found to have higher risks for bipolar disorder among depressive subjects. We found that a modified scoring of the MDQ (ignoring question on functional impairment and co-occurrence of symptoms) yielded a sensitivity of 0.68 and a specificity of 0.63 for bipolar diagnosis, whereas the figures were 0.29 and 0.77, respectively, with the standard MDQ scoring. CONCLUSIONS The results of this study clearly indicate that a high frequency of bipolar disorders in depressive patients who have never been diagnosed with bipolar disorders and clinical features indicating bipolarity could help to differentiate bipolar subjects from unipolar subjects. Adapting the standard scoring, the MDQ showed limited use for detecting bipolar disorder; however, if the scoring modification is adapted, the MDQ can offer tolerable sensitivity.

Visceral Fat Accumulation Induced by a High-fat Diet Causes the Atrophy of Mesenteric Lymph Nodes in Obese Mice

Objective: A high intake of fat in the diet plays a crucial role in promoting obesity and obesity‐related pathologies, and especially visceral obesity is closely associated with obesity‐related complications. Because adipose tissue is anatomically associated with lymph nodes, the secondary lymphoid organ, we hypothesized that fat tissue‐derived factors may influence the cellularity of lymphoid tissue embedded in fat.

The rate of metabolic syndrome in euthymic Canadian individuals with bipolar I/II disorder

ObjectiveTo report on the rate of metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), in asymptomatic adults with bipolar I/II disorder evaluated at the Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto. To our knowledge, this is the first study reporting on the rate of metabolic syndrome in a Canadian clinical sample and exclusively evaluating asymptomatic individuals.MethodsThis was a post-hoc, cross-sectional analysis of adult bipolar subjects who were primarily enrolled in a clinical intervention study. All subjects in this sample were asymptomatic at the time of assessing metabolic parameters.ResultsData from 99 euthymic bipolar subjects (n=51 female, n=48 male) were included for the analysis. The sample mean age±SD was 38±11.15 years. Thirty-one subjects (32.6%) met criteria for the metabolic syndrome with no significant differences as a function of sex. The waist circumference criterion was met in 37 (41.1%) subjects. Diastolic and systolic blood pressure criteria were met in 26 (27.6%) and 28 (29.7%) subjects, respectively. Thirty-one subjects (36.4%) met the high-density lipoprotein (HDL) criterion, while 33 (38.8%) met the triglyceride criterion. Moreover, five (6.1%) met the criterion for high fasting glucose level (diabetes mellitus or glucose/insulin dysregulation at screening was an exclusion criterion). Men were more likely to have high diastolic (P=0.001) and systolic blood pressure (P=0.007) as well as hypertriglyceridemia (P=0.037). Abdominal obesity, HDL, and fasting glucose levels were not significantly different between men and women. Bipolar individuals with concurrent metabolic syndrome had a later age at first treatment and increased number of total hospitalizations.ConclusionAsymptomatic Canadian individuals with bipolar disorder exhibit a high rate of concurrent metabolic syndrome. The results herein buttress recommendations for risk factor screening and modification, ongoing surveillance, as well as primary and secondary prevention strategies for metabolic abnormalities in individuals with bipolar disorder.

Correlates of metabolic abnormalities in bipolar I disorder at initiation of acute phase treatment.

Objective Treatment of bipolar patients is often complicated by metabolic abnormalities such as obesity, diabetes, and dyslipidemia. We therefore evaluated the prevalence of these abnormalities and their correlates, in bipolar I patients, at the time of commencement of pharmacological treatment for acute mood episodes. Methods The study cohort consisted of 184 bipolar I patients hospitalized for treatment of acute mood episodes. Socio-demographic and clinical variables were noted and metabolic parameters, including body mass index, fasting plasma glucose, fasting total cholesterol, and current treatment(s) for diabetes and/or dyslipidemia were measured before initiating medication(s). Results Fifty-six (30.4%) subjects met our criteria for obesity; 80 (43.5%) had hyperglycemia, with 8 (4.3%) receiving anti-diabetic medication; and 38 (20.7%) had hypercholesterolemia, with 2 (1.1%) receiving cholesterol-lowering agents. We found that male sex (χ2=5.359, p=0.021), depressed or mixed state versus manic state (χ2=4.302, p=0.038), and duration of illness (t=2.756, p=0.006) were significantly associated with obesity. Older age (t=3.668, p<0.001), later age of disease onset (t=2.271, p=0.024), and lower level of educational attainment (β=-0.531, p=0.001) were associated with hyperglycemia. Conclusion Our finding that metabolic abnormalities are prevalent when initiating acute pharmacological treatment in bipolar I patients indicates that these factors should be integrated into treatment plans at the onset of disease management.

Heart rate variability in the subsyndromal depressive phase of bipolar disorder

Aims:  To compare the heart rate variability of bipolar patients in the subsyndromal depressive phase with healthy controls and to evaluate the relationship between severity of subsyndromal depressive symptoms and heart rate variability.

Comparative Study of Personality Traits in Patients with Bipolar I and II Disorder from the Five-Factor Model Perspective

Objective The distinguishing features of Bipolar I Disorder (BD I) from Bipolar II Disorder (BD II) may reflect a separation in enduring trait dimension between the two subtypes. We therefore assessed the similarities and differences in personality traits in patients with BD I and BD II from the perspective of the Five-Factor Model (FFM). Methods The revised NEO Personality Inventory (NEO-PI-R) was administered to 85 BD I (47 females, 38 males) and 43 BD II (23 females, 20 males) patients. All included patients were in remission from their most recent episode and in a euthymic state for at least 8 weeks prior to study entry. Results BDII patients scored higher than BD I patients on the Neuroticism dimension and its four corresponding facets (Anxiety, Depression, Self-consciousness, and Vulnerability). In contrast, BD II patients scored lower than BD I patients on the Extraversion dimension and its facet, Positive emotion. Competence and Achievement-striving facets within the Conscientiousness dimension were significantly lower for BD II than for BD I patients. There were no significant between-group differences in the Openness and Agreeableness dimensions. Conclusion Disparities in personality traits were observed between BD I and BD II patients from the FFM perspective. BD II patients had higher Neuroticism and lower Extraversion than BD I patients, which are differentiating natures between the two subtypes based on the FFM.

Sex-different association of DAO with schizophrenia in Koreans

The gene encoding D-amino acid oxidase (DAO), which acts as a receptor for the schizophrenia-associated neurotransmitter, N-methyl-D-aspartate (NMDA), is regarded as a potential candidate gene for schizophrenia. However, the potential association of the DAO gene with schizophrenia has been the subject of some debate. Here, we tested three single nucleotide polymorphisms (SNPs) of DAO in a group of Korean schizophrenia patients, and found no significant association in the overall study subjects. Interestingly, however, we found gender-specific differences in allele distributions, with SNP rs2070586 appearing to act as a risk allele in female schizophrenia patients, but as a protective allele in males. Our data support the hypothesis that DAO plays a role in schizophrenia, possibly in a gender-dependent manner.