Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients

Objectives: Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep—as opposed to periventricular—WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway—a pathway linked to nervous tissue disease in diabetes—is related to deep WMH volume and treatment resistance in BD patients. Methods: Volumes of fluid-attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15). Results: BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (ρ = 0.487, p = 0.029) and fructose (ρ = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (ρ = 0.578, p = 0.008), sorbitol (ρ = 0.542, p = 0.013), and fructose (ρ = 0.692, p = 0.001) in BD subjects but not in other subjects. Conclusions: This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology.     

The Disparity in Long-Term Survival after a First Stroke in Patients with and without Diabetes Persists: The Northern Sweden MONICA Study

Background: Diabetes is an established risk factor for stroke. Compared to nondiabetic patients, diabetic patients also have an increased risk of new vascular events and death after stroke. We analyzed how differences in long-term survival between diabetic and nondiabetic stroke patients have changed over time, and if differences varied with respect to sex and age. Methods: This population-based study included 12,375 first-ever stroke patients, 25-74 years old, who were registered in the Northern Sweden MONICA Stroke Registry 1985-2005. Uniform diagnostic criteria for stroke case ascertainment were used throughout the study period. The diagnosis of diabetes was based on medical records or diabetes diagnosed during the acute stroke event. Patients were separated into four cohorts according to year of stroke and followed for survival until August 30, 2008. Results: The diabetes prevalence at stroke onset was 21%, similar in men and women, and remained stable throughout the study period. The diabetic patients were an average of 2 years older, more often nonsmokers and more likely to have antihypertensive treatment, antithrombotics, atrial fibrillation, and a history of myocardial infarction or transient ischemic attack than the nondiabetic patients. The total follow-up time was 86,086 patient-years during which a total of 1,930 (75.7%) of the diabetic patients and 5,744 (58.5%) of the nondiabetic patients died (p < 0.001). Median survival was 60 months (95% CI: 57-64) in diabetic patients and 117 months (113-120) in the nondiabetic patients. Survival improved significantly in both groups (p < 0.001). A Cox regression, adjusting for possible confounders (age, sex, antihypertensive medication, antithrombotics or other thrombolytic agents, history of myocardial infarction, type of stroke, diabetes, cohort and the diabetes-by-sex, diabetes-by-age and diabetes-by-cohort interactions), showed a hazard ratio of 1.67 (1.58-1.76) comparing survival in diabetic versus nondiabetic patients. The reduced survival in diabetic stroke patients was more pronounced in women (p = 0.02) and younger patients (p < 0.001). There was a tendency that the difference in survival decreased between the earlier cohorts and the 2000-2005 cohort, but the test for interaction did not reach statistical significance (p = 0.08). Conclusion: Long-term survival after a first stroke has improved in both diabetic and nondiabetic patients. Survival is markedly lower in diabetics, especially in women and younger patients, and the disparity persisted over 24 years. Decreasing the disparity in stroke survival is a challenge for stroke and diabetes care. New treatment methods in combination with intense secondary prevention in diabetic patients, especially in younger women, are needed.     

Can body mass index help predict outcome in patients with bipolar disorder?

Objective:  Several studies have reported higher prevalence of obesity in patients suffering from bipolar disorder (BD). To study the relation of elevated body mass index (BMI) in patients with BD more closely, we investigated differences in sociodemographic, clinical, and medical characteristics with respect to BMI, with the hypothesis that BMI is related to prognosis and outcome.
Methods:  We measured the BMI of 276 subjects of a tertiary care sample from the Maritime Bipolar Registry. Subjects were 16 to 83 years old, with psychiatric diagnoses of bipolar I disorder (n = 186), bipolar II disorder (n = 85), and BD not otherwise specified (n = 5). The registry included basic demographic data and details of the clinical presentation. We first examined the variables showing a significant association with BMI; subsequently, we modeled the relationship between BMI and psychiatric outcome using structural equation analysis.
Results:  The prevalence of obesity in our sample was 39.1%. We found higher BMI in subjects with a chronic course (p < 0.001) and longer duration of illness (p = 0.02), lower scores on the Global Assessment of Functioning Scale (p = 0.02), and on disability (p = 0.002). Overweight patients had more frequent comorbid subthreshold social (p = 0.02) and generalized anxiety disorders (p = 0.05), diabetes mellitus type II (p < 0.001), and hypertension (p = 0.001). Subjects who achieved complete remission of symptoms on lithium showed significantly lower BMI (p = 0.01).
Conclusions:  Our findings suggest that BMI is associated with the prognosis and outcome of BD. Whether this association is causal remains to be determined.     

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.     

Clinical predictors of unrecognized bipolar I and II disorders

OBJECTIVES: Bipolar disorder (BD) is correctly diagnosed in only 40-50% of patients. No previous study has investigated the characteristics of bipolar patients in psychiatric care with or without clinical diagnoses of BD. We investigated the demographic and clinical predictors of the absence of a clinical diagnosis of BD I and II among psychiatric patients. METHODS: In the Jorvi Bipolar Study, 1,630 psychiatric in- and outpatients were screened with the Mood Disorder Questionnaire. Suspected cases were diagnosed with the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient version (SCID-I/P) for BD. Patients with no preceding clinical diagnosis of BD, despite previous manic, hypomanic or mixed phases and treatment in psychiatric care, were classified as undiagnosed. The clinical characteristics of unrecognized BD I patients (23 of 90 BD I patients) and BD II patients (47 of 93 BD II patients) were compared to those of patients who had been correctly diagnosed. RESULTS: No previous hospitalizations [odds ratio (OR) = 10.6, p = 0.001] or psychotic symptoms (OR = 4.4, p = 0.045), and the presence of rapid cycling (OR = 11.6, p = 0.001) predicted lack of BD I diagnosis. No psychotic symptoms (OR = 3.3, p = 0.01), female gender (OR = 3.0, p = 0.03), and shorter time in treatment (OR = 1.1, p = 0.03) predicted the lack of a BD II diagnosis. CONCLUSIONS: Correct diagnosis of BD I is related to the severe phases of illness leading to hospitalizations. In BD II, the illness factors may not be as important as time elapsed in treatment, a factor that often leads to a delay in diagnosis or none at all. Excessive reliance on typical and cross-sectional presentations of illness likely explain the non-recognition of BD. The challenge for correctly diagnosing bipolar patients is in outpatient settings.     

Burden of general medical conditions among individuals with bipolar disorder

OBJECTIVE: Treatment of coexisting medical comorbidities may reduce the risk of adverse outcomes among patients with bipolar disorder. We determined the prevalence of general medical conditions in a population-based sample of patients diagnosed with bipolar disorder in the Veterans Administration (VA). METHODS: We conducted a cross-sectional study of patients (n = 4310) diagnosed with bipolar disorder in fiscal year 2001 receiving care at VA facilities located within the mid-Atlantic region. General medical conditions were assessed using ICD-9 codes, and we compared the prevalence of each condition in our bipolar sample with national data on the VA patient population. RESULTS: The mean age was 53 (SD = 13), 10% were women, and 12% African-American. The mean age of the VA national patient population was higher (58 years). The most prevalent conditions among patients with bipolar disorder included cardiovascular (e.g. hypertension, 35%), endocrine (e.g. hyperlipidemia, 23%; diabetes, 17%), and alcohol use disorder (25%). When compared with national data, the prevalence of diabetes was higher in the bipolar cohort than in the national cohort (17.2% versus 15.6%; p = 0.0035). Hepatitis C was more common in the bipolar group than the national cohort (5.9% versus 1.1%; p < 0.001). Lower back pain (15.4% versus 10.6%; p < 0.0001) and pulmonary conditions (e.g. COPD: 10.6% versus 9.4%; p = 0.005) were also more prevalent among the bipolar cohort than the VA national cohort. CONCLUSIONS: Individuals with bipolar disorder possess a substantial burden of general medical comorbidity, and are occurring at an earlier age than in the general VA patient population, suggesting the need for earlier detection and treatment for patients with bipolar disorder.     

Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease

The objective was to describe the indices of platelet aggregation and activation in a large cohort of diabetic patients with coronary artery disease (CAD). Recently, a number of observations have indicated that patients with diabetes mellitus (DM) exhibit persistent platelet activation, and low response after antiplatelet therapy, although no randomized data exist. We sought to define the baseline platelet biomarkers, and the patterns of response to aspirin and clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc analyses were made of platelet activity biomarkers in the dataset which consisted of patients with documented CAD (n = 822), including those with DM (n = 257). Patients with DM exhibited higher baseline platelet activity by adenosine diphosphate (ADP)- (p = 0.0002), and collagen-induced (p = 0.03) aggregometry; Ultegra- (p = 0.0001), and PFA-100 (p = 0.02) analyzers; and expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.01), glycoprotein (GP) IIb/IIIa antigen (p = 0.001), and activity (p = 0.02), vitronectin receptor (p = 0.03), P selectin (p = 0.02), and intact epitope of PAR-1 thrombin receptor (p = 0.02). Antiplatelet response after clopidogrel in diabetics was impaired when compared with non-diabetics. In conclusion, diabetic patients exhibit high pretreatment platelet activity, and do not respond well to the available antiplatelet regimens when compared with similar patients without DM. The clinical implications of these findings are unknown but are potentially important. Considering worsened outcomes in this high-risk population, clinical trials in DM are urgently needed in order to define the optimal degree of platelet inhibition and suitability for more aggressive antiplatelet regimens.     

Mental well-being in people with non-insulin-dependent diabetes

We assessed the prevalence of minor mental disorder and depression in elderly patients with non-insulin-dependent (Type 2) diabetes mellitus as compared with control subjects and evaluated the associates of impaired mental well-being in diabetic patients. The study consists of a community-based group of patients (n= 82) with a 10 years' known duration of disease and nondiabetic control subjects (n= 115). In addition to clinical and laboratory examinations, self-rating questionnaires assessing minor mental disorder (General Health Questionnaire, GHQ) and depression (Zung Self-rating Depression scale) were completed by the patients and control subjects. The mean scores of GHQ and Zung scores tended to be higher in diabetic than in control subjects, but the frequency of case subjects was not different between the diabetic (GHQ: 40%; Zung: 11%) and nondiabetic groups (GHQ: 36%; Zung: 7%). These findings were explained by more severe symptoms in diabetic case subjects as compared to nondiabetic case-subjects. From the various parameters studied, the presence of symptomatic neuropathy was most strongly associated with depression and minor mental disorder in diabetic subjects. The results suggest that the impact of Type 2 diabetes per se on minor mental disorder or depression in elderly subjects-is not overwhelming. However, a subgroup of diabetic patients seems to have markedly impaired mental well-being, and the treatment of its underlying factors may improve overall treatment compliance.     

Topical apraclonidine testing discloses pupillary sympathetic denervation in diabetic patients.

BACKGROUND: Autonomic denervation is common in diabetes mellitus (DM). Pupillary sympathetic denervation (PSD) has been found in Horner syndrome following instillation of apraclonidine 0.5%. We have applied this technique to investigate the prevalence of PSD in DM. METHODS: Apraclonidine 0.5% was instilled in the eyes of 50 patients with DM and 30 age-matched and gender-matched subjects without DM (control subjects). Pupil diameters (PD) were measured before and 60 minutes after instillation. The duration of DM and the degree of diabetic retinopathy (DR) were recorded for each patient. RESULTS: Apraclonidine instillation caused an average of 0.9 mm of mydriasis (range 0 to 4.5 mm) in DM and -0.1 mm miosis (range 0.5 to -1 mm) in control subjects (P < 0.001). Mydriasis of at least 1 mm was observed in 42% of DM patients. The change in PD was highly correlated with the duration of DM (r = 0.368, P = 0.008) and the presence of DR (r = 0.532, P < 0.001). CONCLUSION: Apraclonidine testing, which is easy to perform and not distressing to the patient, identified PSD in nearly half of DM patients, the degree of mydriasis being correlated to the duration of DM and the presence of DR.     

Predictors of trait aggression in bipolar disorder

OBJECTIVES: Although aggressive behavior has been associated with bipolar disorder (BD), it has also been linked with developmental factors and disorders frequently found to be comorbid with BD, making it unclear whether or not it represents an underlying biological disturbance intrinsic to bipolar illness. We therefore sought to identify predictors of trait aggression in a sample of adults with BD. METHODS: Subjects were 100 bipolar I (n = 73) or II (n = 27) patients consecutively evaluated in the Bipolar Disorders Research Program of the New York Presbyterian Hospital-Payne Whitney Clinic. Diagnoses were established using the Structured Clinical Interview for the DSM-IV (SCID-I) and Cluster B sections of the SCID-II. Mood severity was rated by the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Histories of childhood maltreatment were assessed via the Childhood Trauma Questionnaire (CTQ), while trait aggression was measured by the Brown-Goodwin Aggression Scale (BGA). RESULTS: In univariate analyses, significant relationships were observed between total BGA scores and CTQ total (r = 0.326, p = 0.001), childhood emotional abuse (r = 0.417, p < 0.001), childhood physical abuse (r = 0.231, p = 0.024), childhood emotional neglect (r = 0.293, p = 0.004), post-traumatic stress disorder (t = -2.843, p = 0.005), substance abuse/dependence (t = -2.914, p = 0.004), antisocial personality disorder (t = -2.722, p = 0.008) and borderline personality disorder (t = -5.680, p < 0.001) as well as current HDRS (r = 0.397, p < 0.001) and YMRS scores (r = 0.371, p < 0.001). Stepwise multiple regression revealed that trait aggression was significantly associated with: (i) diagnoses of comorbid borderline personality disorder (p < 0.001); (ii) depressive symptoms (p = 0.001); and (iii) manic symptoms (p < 0.001). CONCLUSIONS: Comorbid borderline personality disorder and current manic and depressive symptoms each significantly predicted trait aggression in BD, while controlling for confounding factors. The findings have implications for nosologic distinctions between bipolar and borderline personality disorders, and the developmental pathogenesis of comorbid personality disorders as predisposing to aggression in patients with BD.     

游离脂肪酸与老年2型糖尿病患者轻度认知功能障碍的研究

目的探讨游离脂肪酸(FFA)与老年2型糖尿病(T2DM)患者轻度认知功能障碍(MCI)的关系。方法选择85例老年T2DM患者,应用蒙特利尔认知评估(MoCA)量表评定认知功能,分为T2DM认知功能正常组(T2DM-NC)45例和T2DM认知功能障碍组(T2DM-MCI)40例,另选择糖耐量正常且认知功能正常者35例为对照组(NC)。测定3组FFA、糖化血红蛋白(HbA1c)、血脂等。结果 T2DM-MCI组FFA水平(7.45±0.13)mmol/L高于T2DM-NC组(6.32±0.13)mmol/L及NC组(4.56±0.11)mmol/L。T2DM-MCI患者的MoCA评分与糖尿病病程(r=-0.507,P=0.001)、FPG(r=-0.581,P0.001)、HOMA-IR(r=-0.360,P=0.022)、HbA1c(r=-0.533,P0.001)、TC(r=-0.358,P=0.023)、TG(r=-0.408,P=0.009)、LDL-C(r=-0.377,P=0.016)、FFA水平(r=-0.566,P0.001)呈负相关,与HDL-C(r=0.365,P=0.021)呈正相关。多重线性回归分析结果示,FPG(β=-0.290,P=0.015)、HbA1c(β=-0.272,P=0.019)、FFA(β=-0.375,P=0.001)、病程(β=-0.248,P=0.037)是MoCA评分的危险因素。结论血清FFA是T2DM患者MCI的危险因素。     

The occurrence of cavum septi pellucidi enlargement is increased in bipolar disorder patients

Objectives: This study was conducted to evaluate the prevalence of cavum septi pellucidi (CSP) enlargement in patients with bipolar disorder (BD) and healthy comparison subjects. Methods: The occurrence of enlarged CSP in patients with BD (n = 41, age 35.4 ± 10.8 years) and healthy volunteers (n = 41, age 35.3 ± 10.0 years) was studied using magnetic resonance imaging. The length of the CSP was measured by counting the number of consecutive resliced coronal 0.5‐mm images in which the CSP was present. A CSP length ≥ 6 mm was a priori defined as abnormal enlargement of the CSP. Results: Bipolar subjects exhibited a significantly higher prevalence of abnormal CSP enlargement (8 of 41 subjects, 19.5%) than healthy comparison subjects (1 of 41 subjects, 2.4%) (logistic regression analysis: Wald statistic = 5.07, df = 1, p = 0.024). The prevalence of abnormally enlarged CSP was not significantly different between drug‐naïve and drug‐exposed bipolar subjects or when comparing bipolar I and II sub‐diagnoses. Bipolar subjects with abnormal CSP enlargement had a significantly earlier onset of BD than those without (14.3 ± 3.6 versus 20.1 ± 7.4 years, respectively). Conclusions: The current study is the first to report an increased prevalence of abnormally enlarged CSP in a well‐characterized bipolar population. Our finding that an abnormal enlargement of CSP, a neurodevelopmental abnormality, is associated with early onset of illness implicates early maturational processes as contributing to BD.     

Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients.

OBJECTIVE: Disturbance in glucose homeostasis in psychiatric populations has been suggested since the early part of this century. Increased comorbidity of diabetes mellitus in persons with major mood disorders has also been suggested. The goal of this study was to determine whether subjects diagnosed with bipolar disorder have an elevated rate of comorbid diabetes mellitus. METHOD: Three hundred forty-five hospitalized patients, aged 20-74 years, who met the DSM-III-R criteria for bipolar disorder, manic or mixed subtype, were evaluated for a comorbid diagnosis of diabetes mellitus. The frequency of diabetes mellitus in the study group was determined and compared with the expected frequency, calculated as a weighted average based on sex and age from national norms. Variables characterizing the course and severity of the affective disorder in the group of diabetic bipolar subjects and a group of nondiabetic age-matched bipolar subjects were compared. RESULTS: The prevalence of diabetes mellitus among these bipolar patients was 9.9%, significantly greater than expected from national norms (3.4%). The patients with comorbid diabetes mellitus had significantly more lifetime psychiatric hospitalizations than the nondiabetic subjects, but age at first hospitalization and duration of psychiatric disorder were similar in the two groups. CONCLUSIONS: The frequency of diabetes mellitus in hospitalized patients diagnosed with bipolar disorder is higher than in the general population. Manic-depressive patients with diabetes mellitus have a more severe course of illness, as indicated by a greater number of psychiatric hospitalizations. Possible reasons for this increased comorbidity include a genetic relationship between the disorders, a causal relationship in which hypercortisolemia induces diabetes or diabetic vascular lesions contribute to mania, an overlapping functional disturbance affecting similar regions of the brain, or the effect of psychotropic medications.     

Concurrent tracking of alcohol use and bipolar disorder symptoms

OBJECTIVES: Alcohol use disorders (AUDs) are common co-occurring conditions in patients with bipolar disorder (BD), but it is unclear whether or not AUD and BD symptoms are temporally correlated. The primary aim of this analysis was to examine concurrent symptom tracking and how the relative onsets of AUD and BD influence the concurrent tracking of symptoms. METHODS: Participants met DSM-IV criteria for bipolar I disorder, manic or mixed, with no prior hospitalizations and minimal treatment. Patients were rated for alcohol use and bipolar symptom severity on a weekly basis for up to 7 years. For analysis purposes, patients were placed into groups with no AUD (BD Only; n = 21), onset of AUD either concurrent with or after the onset of bipolar symptoms (BD First; n = 32), and onset of AUD at least 1 year before the onset of bipolar symptoms (AUD First; n = 18). RESULTS: None of the patient groups demonstrate consistent positive or negative temporal correlations between alcohol use and affective symptoms. However, there were significant between-group differences on the relationship of symptom tracking and age of BD onset. For the AUD First group, the correlation between age of BD onset and symptom tracking was positive 0.41. However, for the BD First and BD Only groups the correlations were negative (-0.32 and -0.41, respectively). Moreover, for patients whose BD onset was < or =18 years old, the correlation between age of onset and tracking was -0.47. CONCLUSIONS: These findings suggest that although there is no direct temporal correlation of AUD and BD symptoms in subgroups of BD patients, age at illness onset contributes to the complex relationship between BD and AUD. For younger patients there may be a greater likelihood that alcohol use and bipolar symptoms increase or decrease in unison.     

糖耐量与脑梗死患者颈动脉粥样硬化的关系

目的探讨糖耐量异常的脑梗死患者糖耐量的异常变化与颈动脉粥样硬化的关系。方法选择脑梗死患者160例,通过口服葡萄糖耐量试验(OGTT)将患者分为糖耐量正常组(NGT,n=60例),糖耐量异常组(IGT,n=53例),糖尿病组(DM,n=47例),测定各项血液生化指标,采用双功能彩色多普勒超声检测颈动脉内膜中层厚度(IMT)及斑块。结果脑梗死患者IGT组、DM组颈动脉IMT、斑块检出率及不稳定性斑块发生率均高于NGT组(P<0.05)。IGT组与DM组的颈动脉IMT、颈动脉斑块检出率及不稳定性斑块发生率差异无统计学意义(P>0.05)。脑梗死患者IGT组颈动脉IMT与血糖基化血红蛋白(HbA1C)水平呈正相关(r=0.264,P=0.01),与服糖后2h血糖(2h-PG)呈正相关(r=0.262,P=0.001)。结论脑梗死合并糖耐量异常患者存在明显的动脉粥样硬化表现,IGT是促进动脉粥样硬化发生的重要危险因素,具有促斑块不稳定作用,也是脑梗死的危险因素。     

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.     

Comorbidity with ADHD decreases response to pharmacotherapy in children and adolescents with acute mania: evidence from a metaanalysis.

OBJECTIVE: To assess whether comorbid attention-deficit hyperactivity disorder (ADHD) influences response to treatment in young patients with acute mania. METHODS: We conducted a metaanalysis of 5 open trials of 100, 35, 41, 60, and 37 children and adolescents. The pooled group included 273 children and adolescents with bipolar disorder (BD), divided into 2 subgroups: those with (n = 132), and those without (n = 141), ADHD comorbidity. RESULTS: There was a moderate and significant reduction in relative risk (RR) favouring treatment response in children and adolescents with BD but without ADHD comorbidity (RR 0.822; 95% CI, 0.69 to 0.97; P = 0.021). The negative effect of ADHD comorbidity on treatment response was more significant in studies including adolescents only or subjects with BD I only. CONCLUSION: These findings suggest that children and adolescents with BD and ADHD tend to be less responsive to drugs used in treatment of acute mania.     

Community survey of bipolar disorder in Canada: lifetime prevalence and illness characteristics.

OBJECTIVE: This study reports on the lifetime prevalence and illness characteristics of bipolar disorder (BD) in a large, representative sample of Canadians. METHOD: Data were obtained from the Canadian Community Health Survey: Mental Health and Well-Being. This representative, cross-sectional survey, conducted by Statistics Canada in 2002, examines the mental health of Canadians aged 15 years and over. The national response rate was 77%. We determined the prevalence rate of BD, correlates of a bipolar diagnosis, and illness characteristics. RESULTS: The weighted lifetime prevalence rate of BD was 2.2% (95% confidence interval [CI], 1.94% to 2.37%). Younger age, low income adequacy, lifetime anxiety disorder, and presence of a substance use disorder in the past 12 months were each significantly associated with the presence of a BD diagnosis (P < 0.001 for each). The largest effect found was for the presence of an anxiety disorder (odds ratio 7.94; 95% CI, 6.35 to 9.92). A lifetime history of anxiety disorder was reported by 51.8% (955% CI, 47.1% to 56.5%) of the respondents with BD, with both panic disorder and agoraphobia each being more frequent among women, compared with men (P = 0.01 and P < 0.001, respectively). The mean age at onset of illness was 22.5 years, SD 12.0. CONCLUSIONS: According to the estimated lifetime prevalence of BD found in this study, over 500 000 Canadians likely suffer from this condition. Identifying those at highest risk for BD may assist in developing more effective community-based identification and intervention strategies.