Associations between bipolar disorder and metabolic syndrome: A review

OBJECTIVES: To examine the pathophysiologic mechanisms that may link bipolar disorder and metabolic syndrome and to discuss whether the consequences of metabolic syndrome underlie a substantive portion of the premature morbidity and mortality observed in persons with bipolar disorder. DATA SOURCES: A MEDLINE search, citing articles from 1966 onward, supplemented by a review of bibliographies, was conducted to identify relevant studies. Bipolar disorder, mood disorder, metabolic syndrome, diabetes, cardiovascular illness, and obesity were used as keywords. Criteria used to select studies included (1) English language, (2) published studies with original data in peer-reviewed journals, and (3) studies that confirmed the nature of the mood disorder examined. RESULTS: Ninety-seven studies met criteria and were reviewed for evidence of dysregulation in various physiologic systems. Bipolar disorder and metabolic syndrome share features of hormonal, immunologic, and autonomic nervous system dysregulation. CONCLUSION: Lifestyle features may account, in part, for the premature mortality observed in bipolar disorder, but the somatic correlates of the illness may also predispose patients to metabolic syndrome and the consequent increased risk of diseases such as diabetes and vascular disease.     

双相障碍患者代谢综合征风险研究

目的 调查双相障碍患者长期治疗中代谢综合征的风险发生率及分析可能的相关因素.方法 采用横断面研究.以单用心境稳定剂或联用抗精神病药连续6月以上的门诊双相障碍患者为调查对象.采用统一问卷及实验室检测.代谢综合征诊断标准采用2004年中华医学会糖尿病分会代谢综合征标准.结果 共入组128例,双相障碍患者中代谢综合征的发生率为36.7%(47例).药物类别及用药时间与代谢综合征的发病风险有关(回归系数B值分别为-0.614,-0.797;P值分别为0.028,0.001).结论 与普通人群相比,双相障碍患者有较高的代谢综合征发病风险.用药时间越长代谢综合征的发生风险越高.联用抗精神病药能增加代谢综合征的发生率.临床上应注意监测代谢指标及对代谢异常进行干预.     

Age-specific prevalence of metabolic syndrome in Italian patients with bipolar disorder

Aim: Metabolic syndrome (MetS) is highly prevalent in patients with bipolar disorder (BD). Little research has evaluated the risk profile of MetS and cardiovascular disease in different gender and age groups in these patients. Our aim is to evaluate the prevalence of MetS in Italian patients with BD stratified by gender and age, and to determine the correlates of MetS. Methods: Subjects with BD were included and stratified by sex and age according to the following age groups: <30; 30–39; 40–49; 50–59; ≥60 years. Socio‐demographic and clinical characteristics, lifestyle information, and comorbidity for cardiovascular diseases and diabetes were collected. MetS was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. Results: MetS was evaluated in 200 patients, with a prevalence of 26.5%. Men had higher rates of hypertension and hypertriglyceridemia, women had more abdominal obesity. Women had a peak of prevalence in the ≥60 years group, while men displayed high rates even in the young age groups. In young patients, MetS was associated with Cluster B personality disorders and less physical exercise. Conclusion: Our paper highlights the importance of evaluating MetS even in young patients with bipolar disorder, especially males. The strong association with lack of physical exercise suggests that the implementation of healthy behaviors might be relevant in order to prevent MetS and future adverse cardiovascular outcomes.     

甲状腺功能水平与双相情感障碍相关性的对照研究

目的 探索甲状腺功能与双相情感障碍的相关性.方法 以符合美国精神疾病分类与诊断标准第4版修订本(DSM-Ⅳ-TR)的双相情感障碍诊断标准的患者59例为研究对象,并选取41名健康人作为对照,应用酶联免疫吸附法(ELISA)分别测定所有研究对象的血清甲状腺激素水平,包括TT3、FT3、TT4、FT4及TSH.选用HAMD、HAMA及Bech-Rafaelsen躁狂量表评估患者组临床症状.结果 双相躁狂组中TT4、FT4水平明显高于对照组,FT3水平明显高于抑郁组,差异有统计学意义(P<0.01).双相抑郁组中TT3、FT3水平明显低于对照组,FT4水平则明显高于对照组,差异有统计学意义(P<0.01).按性别分层比较,女性双相躁狂组FT4水平与对照组相比明显升高,差异有统计学意义(P<0.05);女性双相抑郁组TT3明显低于对照组或双相躁狂组,FT4明显高于对照组,FT3则明显低于对照组,差异均有统计学意义(P<0.05),而男性躁狂组中仅TT4水平显著高于对照组(P<0.05).在双相抑郁患者中,HAMD总分与FT4呈负相关(r=-0.34,P=0.03).结论 双相情感障碍患者的甲状腺功能存在一定的改变,不同临床相甲状腺功能改变亦不相同,且这种变化以女性患者明显.     

住院双相障碍患者伴发代谢综合征情况调查

目的:探讨住院双相障碍(BD)患者伴发代谢综合征(MS)情况及相关因素。方法:对231例住院BD患者(BD组)进行一般情况调查、代谢相关指标的测量,结果与147名健康对照者(NC组)比较。结果:BD组体质量指数(BMI)、腰围(WAIST)、血清三酰甘油(TG)、空腹血糖(FPG)水平、血压异常率、中心型肥胖率及MS发生率显著高于NC组,血清高密度脂蛋白(HDL)水平显著低于NC组(P0.05或P0.01)。BD患者中男性MS发生率(44.8%)明显高于女性(33.0%)(P0.05);相对于非MS患者,伴有MS的患者年龄大、BD病程长,差异有统计学意义(P0.05或P0.01)。结论:BD患者MS发生率高,男性、年龄大、病程长为可能的危险因素。     

Serum lipids,metabolic syndrome and lifetime suicide attempts in patients with bipolar disorder

Objective

Bipolar disorder is associated with a high risk of suicide. Many clinical characteristics and, recently, biomarkers have been studied with the aim to find useful predictors of suicidality. The role of serum lipids has also been explored albeit with conflicting results; however, few studies have been focused on patients with bipolar disorder.Aim of our study is to investigate whether serum cholesterol, triglycerides, HDL-c and metabolic syndrome are associated with lifetime suicide attempts in a large naturalistic sample of patients with bipolar disorder.

Methods

220 patients with bipolar disorder were included. History of lifetime suicide attempts was systematically and retrospectively assessed for each patient. Blood exams testing total cholesterol, triglycerides, and HDL-c levels were performed, and metabolic syndrome was diagnosed according to NCEP ATP-III modified criteria. Serum lipid levels and metabolic syndrome were compared in patients with or without history of suicide attempt. According to a theory that links impulsivity and violence with low cholesterol, the association between lipid levels and violent suicidal behavior was also assessed.

Results

Lifetime suicide attempts rate was 32.3%. There were no statistically significant differences between patients with and without lifetime suicide attempts in cholesterol, triglycerides, HDL-c levels, and the prevalence of metabolic syndrome. No differences in the same variables were found in violent suicide attempters compared with nonviolent ones. Clinical characteristics such as gender, low education, higher number of manic and depressive episodes, and taking more medications for bipolar disorder were associated with lifetime suicide attempts.

Conclusions

Our results do not support the hypothesis of a strong association between serum lipid levels and suicide in patients with bipolar disorder.     

Serum lipids, metabolic syndrome and lifetime suicide attempts in patients with bipolar disorder

Obesity in children and adolescents is a worldwide health problem, characterized by various somatic, psychosocial and psychiatric complications, and is often associated with adult obesity and related complications. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding behavior, food intake regulation, energy metabolism and weight control. A common polymorphism of the BDNF genotype (Val66Met) has been associated with various forms of eating disorders, alterations in body mass index (BMI) values and obesity in adult populations. The aim of this study was to determine the association between the gene variants of the BDNF Val66Met polymorphism and obesity in 300 healthy Caucasian children and adolescents of the same ethnic background of Croatian origin, subdivided according to the BMI percentile, but without any form of eating disorders. The frequency of the Met/Met, Met/Val and Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met and Met/Val genotypes versus the homozygous Val/Val genotype) differed significantly between underweight, normal weight, overweight and obese children, and the presence of one or two Met alleles contributed to this significant effect. These results showed for the first time the significant association between the presence of one or two Met alleles and obesity in ethnically homogenous groups of healthy Caucasian children and adolescents. These data confirmed the major role of BDNF in energy metabolism, food regulation and BMI.     

Differences in cholesterol and metabolic syndrome between bipolar disorder men with and without suicide attempts

Patient with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome (MetS) and its components compared to general population. Among psychiatric disorders, bipolar disorder ranks highest in suicidality with a relative risk ratio of completed suicide of about 25 compared to the general population. Regarding the biological hypotheses of suicidality, low blood cholesterol level has been extensively explored, although results are still conflicting. The aim of this study was to investigate whether there were differences in the serum cholesterol levels in hospitalized bipolar disorder men patients with history of suicide attempts (N = 20) and without suicide attempts (N = 20). Additionally, we investigated if there were differences in the prevalence of MetS according to NCEP ATP-III criteria in these two groups of patients. Results of the study indicated significantly lower serum cholesterol levels (p = 0.013) and triglyceride levels (p = 0.047), in the bipolar disorder men with suicide attempts in comparison to bipolar disorder men without suicide attempts. The overall prevalence of MetS was 11/40 (27.5%). On this particular sample it was higher in the non-attempters 8/20 (40.0%) than in attempters 3/20 (15.0%) bipolar men group, but without statistical significance. Lower concentrations of serum cholesterol might be useful biological markers of suicidality in men with bipolar disorder.     

Association between bipolar affective disorder and multiple sclerosis

Ten patients from Monroe County, N.Y., had both multiple sclerosis and bipolar affective disorder. Epidemiologic data indicate that the expected number would be 5.4. This difference may indicate an association between these disorders.     

Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder

OBJECTIVES: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment. METHODS: Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program Adult Treatment Protocol (ATP-III) criteria, the adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dL, and the recently proposed criteria from the International Diabetes Federation (IDF). RESULTS: The analysis of 60 patients showed a prevalence of the metabolic syndrome of 16.7% (ATP-III), 18.3% (adapted ATP-III) and 30.0% (IDF), respectively. A total of 6.7% of the patients met criteria for diabetes and 23.3% for pre-diabetic abnormalities. CONCLUSIONS: The metabolic syndrome and glucose abnormalities are highly prevalent among patients with BD. They represent an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of metabolic abnormalities and its associated risks should be part of the clinical management of patients with BD.     

Brain metabolic alterations in medication-free patients with bipolar disorder

BACKGROUND: Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings. OBJECTIVE: To investigate brain chemistry in medication-free individuals with BD. DESIGN: Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32 x 32, 1-cm(3) voxel matrix) acquired axially through the cingulate gyrus was used to quantify regional brain chemistry. SETTING: The Center for Anxiety and Depression at the University of Washington in Seattle and the Bipolar Research Programs at McLean Hospital and the Massachusetts General Hospital in Boston. PARTICIPANTS: Thirty-two medication-free outpatients with a diagnosis of BD type I (BDI) or BD type II (BDII), predominantly in a depressed or mixed-mood state, were compared with 26 age- and sex-matched healthy controls. MAIN OUTCOME MEASURES: Tissue type (white and gray) and regional analyses were performed to evaluate distribution of lactate; glutamate, glutamine, and gamma-aminobutyric acid (Glx); creatine and phosphocreatine (Cre); choline-containing compounds (Cho); N-acetyl aspartate; and myo-inositol. Chemical relationships for diagnosis and mood state were evaluated. RESULTS: Patients with BD exhibited elevated gray matter lactate (P =.005) and Glx (P =.007) levels; other gray and white matter chemical measures were not significantly different between diagnostic groups. Isolated regional chemical alterations were found. An inverse correlation between 17-item Hamilton Depression Rating Scale scores and white matter Cre levels was observed for BD patients. CONCLUSIONS: Gray matter lactate and Glx elevations in medication-free BD patients suggest a shift in energy redox state from oxidative phosphorylation toward glycolysis. The possibility of mitochondrial alterations underlying these findings is discussed and may provide a theoretical framework for future targeted treatment interventions.     

The societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands

OBJECTIVE: To assess the societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands. METHOD: Forty persons with a lifetime diagnosis of bipolar disorder (SCID/DSM-IV) and representative for the Dutch general population were interviewed to collect data on direct (use of medical resources) and indirect (productivity losses because of absence from work and reduced efficiency at work) costs of illness. Respondents' quality of life was also assessed. Prevalence (5.2%) of bipolar disorder was used to estimate total costs. RESULTS: Total costs of bipolar disorder were estimated at US 1.83 billion dollars (total direct costs = US 454 million dollars; total indirect costs = US 1.37 billion dollars). Participants' quality-of-life scores were lower than those of the general population. CONCLUSION: The societal costs form patients suffering of bipolar disorder in the Netherlands were high, especially the indirect costs because of absence from work. The quality of life of bipolar patients was lower than the general population.     

Metabolic syndrome in Italian patients with bipolar disorder

OBJECTIVE: This study aimed to evaluate the prevalence of metabolic syndrome (MetS) in Italian patients with bipolar disorder (BD) and to determine the sociodemographic and clinical correlates of MetS in this patient population. METHOD: Subjects with BD I and II were included. Sociodemographic and clinical characteristics, lifestyle information (alcohol and smoking habits and rate of physical exercise) and comorbidity for cardiovascular diseases and diabetes were collected. Patients were assessed for MetS according to both National Cholesterol Education Program Adult Treatment Panel III and International Diabetes Federation (IDF) criteria. RESULTS: MetS was evaluated in 99 patients out of 108 who were enrolled. MetS was present in 25.3% of the sample. Abdominal obesity was present in 50%, hypertension in 40%, high triglycerides in 34.7%, low HDL-C levels in 32.3% and fasting hyperglycemia in 11% of the sample. Prevalence of MetS was 30% when IDF criteria were employed. Of the investigated variables, age, duration of illness, rate of obesity and cardiovascular disease were higher in patients with MetS. After the regression analysis, only age and obesity were associated to MetS. CONCLUSIONS: MetS is highly prevalent in Italian patients with BD. Our 25.3% prevalence rate is consistent with the 21-22% reported in other European studies and lower than that in U.S. studies. Elderly and obese patients with BD are at particularly high risk for MetS.     

未治疗的双相障碍患者共病代谢综合征的临床分析

目的:探讨未治疗的双相障碍(BD)患者共病代谢综合征(MS)的情况及相关因素分析。方法:收集125例未治疗的BD患者(BD组)的一般人口学资料及临床资料,检测其代谢指标,包括体质量指数(BMI)、收缩压(SBP)和舒张压(DBP)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、空腹血糖(FPG),并与201名健康体检者(对照组)比较,分析BD患者发生MS的危险因素。结果:BD组年龄明显低于对照组,校正年龄和性别后,BD组SBP及FPG异常率及MS发生率明显高于对照组(P均<0.01)。男性患者SBP、TG明显高于女性,HDL水平明显低于女性(P均<0.01);TG异常率及代谢指标异常≥2项的比率明显高于女性(P均<0.05)。Logistic回归分析显示,BD患者发生MS的危险因素是BMI、性别和年龄。结论:BD患者共病MS的风险较健康人更高,其中男性、年龄和BMI是MS的危险因素。     

Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia

Müller DJ, Zai CC, Shinkai T, Strauss J, Kennedy JL. Association between the DAOA/G72 gene and bipolar disorder and meta‐analyses in bipolar disorder and schizophrenia.
Bipolar Disord 2011: 13: 198–207. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: The d ‐amino acid oxidase activator (DAOA, or G72) is involved in the oxidation of d ‐serine, an endogenous modulator of N‐methyl‐d ‐aspartate receptors and thus represents an important candidate in psychotic disorders. Several studies reported the DAOA/G72 gene to be associated with schizophrenia (SZ) and bipolar disorder (BD); however, the associated polymorphisms varied between SZ and BD. This study attempts to replicate the DAOA/G72 findings in BD and to conduct subgroup analyses based on the presence or absence of psychotic symptoms. Methods: Five polymorphisms of the DAOA/G72 gene (rs1341402, rs1935062, rs2391191, rs947267, and rs778294) were analysed for association with BD in a family‐based study design (303 core families including 916 individuals). We also conducted a meta‐analysis of DAOA/G72 polymorphisms in BD and SZ. Results: Marker rs1935062 was significantly associated with BD diagnosis in our sample (Z‐score for C‐allele = ?2.33, p = 0.02, uncorrected for genome‐wide multiple comparisons). When we examined the subset of BD patients with psychotic symptoms (157 families), no significant results were obtained. Our meta‐analysis yielded negative findings for DAOA/G72 markers in BD and positive findings for marker rs2391191 in SZ in East Asians. However, significant heterogeneity across studies limits interpretation. Conclusions: Our results provide evidence that suggests a possible role of the DAOA/G72 gene in BD and SZ. Marker rs1935062 may be specifically associated with BD, while marker rs2391191 may be associated with SZ but not with BD. Together with previous studies, these findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders.     

Improvements in metabolic abnormalities among overweight schizophrenia and bipolar disorder patients

PurposeAs weight-gain and metabolic abnormalities during treatment with psychotropic drugs are of great concern, we evaluated effects of psycho-education and medical monitoring on metabolic changes among severely mentally ill patients.Materials and methodsDuring repeated, systematic psycho-education about general health among 66 consecutive patients diagnosed with DSM-IV-TR schizophrenia (n = 33) or type-I bipolar disorder (n = 33), we evaluated (at intake 1, 2, 3, and 6 months) clinical psychiatric status, treatments and doses, recorded physiological parameters, and assessed attitudes about medication.ResultsAt intake, patients with schizophrenia vs bipolar disorder were receiving 3–7 times more psychotropic medication, with 14% higher initial body-mass index (BMI: 29.1 vs 25.6 kg/m2), 12 times more obesity, and significantly higher serum lipid concentrations. During 6-months follow-up, among bipolar disorder patients, polytherapy and serum lipid concentrations declined more than among schizophrenia patients (e.g., total cholesterol + triglycerides, by 3.21 vs 1.75%/month). BMI remained stable. Declining lipid levels were associated with older age, bipolar disorder, being unemployed, higher antipsychotic doses, and lower initial BPRS scores (all P ≤ 0.001).ConclusionsPsychotropic treatments were more complex, and metabolic measures more abnormal among bipolar disorder than schizophrenia patients. Intensive psycho-education, clinical monitoring, and encouragement of weight-control for six months were associated with improvements in metabolic measures (but not to BMI), and more realistic attitudes about medication.     

Equally increased risk for metabolic syndrome in patients with bipolar disorder and schizophrenia treated with second-generation antipsychotics

Objective: Although second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and bipolar disorder, their effects on dyslipidemia, glucose intolerance, metabolic syndrome (MetS), and coronary heart disease (CHD) risk are less well documented for bipolar disorder. We compared bipolar disorder and schizophrenia patients receiving SGAs to determine whether MetS prevalence is influenced by the primary psychiatric diagnosis or concomitant mood stabilizer treatment. Methods: Admission assessment of MetS criteria (abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, arterial hypertension) and the calculated 10-year CHD risk in bipolar disorder and schizophrenia patients treated with SGAs and closely matched for age, sex, and race. Results: Compared to schizophrenia patients (n = 111), those with bipolar disorder (n = 74) had lower body mass index (27.1 ± 5.3 versus 29.9 ± 8.1, p = 0.0053), were more likely treated with mood stabilizers (60.8 versus 36.0, p = 0.0009), and less likely treated with clozapine (1.3% versus 15.3%, p = 0.0017) or two antipsychotics (10.8% versus 34.2%, p = 0.0003). Despite these differences, bipolar disorder and schizophrenia patients had comparable rates of MetS (43.2% versus 45.9%, p = 0.71) and predicted CHD events (10-year risk >10%: 18.9% versus 23.4%, p = 0.47). Using ≥100 mg/dL as the adapted glucose criterion, MetS rates were 54.0% in both diagnostic groups (p = 1.0). Mood stabilizer co-treatment was not associated with MetS or its individual criteria. Conclusions: Patients with bipolar disorder and schizophrenia who are treated with SGAs have similarly high rates of MetS. These findings suggest a shared susceptibility to antipsychotic-related metabolic dysregulations that is not primarily related to psychiatric diagnosis or concomitant mood stabilizer treatment.