Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting

Objective

To assess quetiapine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Methods

We naturalistically administered open quetiapine to outpatients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

96 patients (36 BD I, 50 BD II, 9 BD NOS, 1 Schizoaffective Bipolar Type, mean ± SD age 42.3 ± 13.8 years, 66.7% female) received quetiapine, combined with an average of 2.5 (in 66.7% of patients at least 2) other psychotropic medications and 0.9 non-psychotropic medications, started most often during depressive symptoms (53.1%) or euthymia (37.5%). Mean quetiapine duration and final dose were 385 days and 196 mg/day (50.0% of patients took ≤75 mg/day). Quetiapine was discontinued in 38.5% of trials, after on average 307 days, most often (in 19.8%) due to CNS adverse effects (primarily sedation). In 38.5% of trials quetiapine was continued on average 328 days with no subsequent psychotropic added. In 22.9% quetiapine was continued on average 613 days, but had subsequent psychotropic added after on average 113 days, most often for depressive symptoms. In 67 trials started at Stanford, quetiapine tended to primarily maintain euthymia and relieve depressive symptoms. In 29 trials started prior to Stanford, continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms. Aside from sedation, quetiapine was generally well tolerated.

Conclusions

In bipolar disorder outpatients quetiapine had a moderate (38.5%, with 385-day mean duration) discontinuation rate, and commonly did not require subsequent additional pharmacotherapy, suggesting effectiveness in a clinical setting.     

Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients

Introduction

In clinical trials, fixed-dose enoxaparin (40 mg once daily) reduces the risk of venous thromboembolism (VTE) in medically-ill patients. However, morbidly obese patients were under-represented in these trials and using fixed-dose enoxaparin in obese patients may be inadequate. We completed a pharmacokinetic study in morbidly obese, medically-ill patients to determine if weight-based dosing of enoxaparin for VTE prophylaxis was feasible, without excessive levels of anticoagulation, as determined by peak anti-Xa levels.

Materials and Methods

Twenty eight morbidly obese (BMI ≥ 35 kg/m²) patients were enrolled and completed the study protocol. Enoxaparin 0.5 mg/kg was administered once daily subcutaneously and peak anti-Xa levels were measured approximately 4-6 hours after the enoxaparin dose.

Results and Conclusions

Overall, 46% of patients were female, the average age (± SD) was 54 (± 11) years, and the average weight and BMI were 135.6 kg (± 25.3) and 48.1 kg/m² (± 11.1), respectively. The average daily dose of enoxaparin was 67 mg (± 12). The average peak anti-Xa level was 0.25 (SD ± 0.11, range 0.08 to 0.59) units/mL. Peak anti-Xa levels did not significantly correlate with weight or BMI. There were no bleeding events, symptomatic VTE, or significant thrombocytopenia.In morbidly obese, medically-ill patients, use of weight-based enoxaparin dosed at 0.5 mg/kg once daily is feasible and results in peak anti-Xa levels within or near recommended range for thromboprophylaxis, without any evidence of excessive anti-Xa activity. These data suggest that this weight-based regimen may be more effective than standard fixed-dose enoxaparin. Clinical outcome studies are warranted to determine the clinical safety and efficacy of this regimen.     

Eating disorder psychopathology does not predict the overweight severity in subjects seeking weight loss treatment

Background

Many obese subjects show relevant psychological distress. The aims of this study were to assess the psychopathological and clinical features of a sample of overweight or obese subjects seeking weight loss treatment and to evaluate the possible, significant associations between the levels of overweight and the specific and general eating disorder psychopathology.

Methods

A total of 397 consecutive overweight (body mass index ≥25 kg/m²) patients seeking treatment for weight loss at the Outpatient Clinic for Obesity of the University of Florence were studied. The prevalence of binge eating disorder was assessed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. All subjects were assessed through the self-report version of the Eating Disorder Examination Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory.

Results

The current prevalence of binge eating disorder was 24.2%; 35% of the subjects were overweight during childhood. High prevalence rates of clinical significant depressive (38%) and anxious (71.5%) symptoms were observed. Binge eating disorder, the severity of specific eating disorder psychopathology, and depressive and anxious symptoms were not associated with the severity of overweight.

Conclusions

The severity of the specific and general eating disorder psychopathology does not predict the levels of overweight. A positive association between severe eating disorder psychopathology and clinical depression was observed.     

Gender-specific lipid profiles in patients with bipolar disorder

Objective

High rates of dyslipidemia and insulin resistance (IR) are reported in patients with bipolar disorder (BD). We assessed gender effects upon rates of dyslipidemia/IR in outpatients with BD.

Methods

Data from 491 outpatients (ages 18-88) seen in the Stanford Bipolar Disorders clinic between 2000 and 2007 were evaluated. Patients were followed longitudinally and received naturalistic treatment. BD patients (n = 234; 61% female; 42% Type I, 47% Type II, 11% NOS) with a mean age of 40.3 ± 14.0 years, mean BMI 26.8 ± 6.4, and 81% Caucasian, who had one of four lipid measures (total cholesterol, LDL, HDL, TG) at clinicians’ discretion, a psychiatry clinic visit within 2 months of laboratory, and were not medicated for dyslipidemia were included. IR was imputed from TG/HDL ratio.

Results

Women, compared with men, had significantly lower mean triglycerides (105.58 ± 64.12 vs. 137.99 ± 105.14, p = 0.009), higher mean HDL cholesterol (60.17 ± 17.56 vs. 46.07 ± 11.91 mg/dl, p < 0.001), lower mean LDL cholesterol (109.84 ± 33.47 vs. 123.79 ± 35.96 mg/dl, p = 0.004), and lower TG/HDL ratio (1.98 ± 1.73 vs. 3.59 ± 3.14 p < 0.001). Compared to men, women had a significantly lower prevalence of abnormal total cholesterol, LDL, TG, HDL, and TG/HDL ratio. No significant differences were found between men and women with regard to age, BMI, ethnicity, educational attainment, smoking habits, bipolar illness type, illness severity or duration, or weight-liable medication exposure.

Discussion

In outpatients with BD, women had more favorable lipid profiles than men despite similar demographic variables. This sample of primarily Caucasian and educated patients, receiving vigilant clinical monitoring, may represent a relatively healthy psychiatric population demonstrating gender differences similar to those in the general population.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

Objective

To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method

Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion

In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Overweight and obesity in patients with bipolar disorder or schizophrenia compared with a non-psychiatric sample

Objective

Multiple studies suggest an association of overweight and obesity with bipolar disorder (BD) and schizophrenia. The goal of this paper was to determine the magnitude of this association and its relationship with previous course-of-illness and other variables of clinical interest.

Methods

The prevalence of overweight and obesity was compared among patients with BD (n = 108), patients with schizophrenia (n = 250) and a non-psychiatric control group (n = 290). Moreover, within each group we analyzed the variables associated with overweight [including obesity, i.e., body mass index (BMI) ≥ 25] and obesity (BMI ≥ 30) adjusting for a possible confounding effect of sex, age and educational level by logistic regression.

Results

In comparison with the non-psychiatric sample, a strong association of both BMI ≥ 25 and obesity was observed with BD and schizophrenia (adjusted odds ratios between 3.4 and 4.6; P-values < 0.001). Overweight was significantly associated with male sex and increasing age in both control and BD groups; and with female sex among schizophrenia patients. Moreover, for BD patients, earlier onset of first BD symptoms, presence of a non-psychiatric illness, current use of mood-stabilizing medication, and being a non-smoker were significantly associated with overweight; and male sex and the presence of a non-psychiatric illness, with obesity. Within the schizophrenia patients, obesity was significantly associated with female sex, intermediate age range and lower PANSS score.

Conclusions

Among patients with BD or schizophrenia, the chronic course of their illness and their current treatment with psychotropic medication might be more relevant for becoming overweight or obese than the specific psychiatric illness.     

Psychotropes, grossesse et adaptation néonatale du nouveau-né. Étude exploratoire (Unité Mère-Enfant, Bordeaux : 2001-2007)

Background

Knowledge about the impact of psychotropic drugs intake during pregnancy on newborns and infant health is limited. The present preliminary study compares neonatal adaptation of babies whose mothers took psychotropic drugs during pregnancy to adaptation of babies whose mothers didn’t, for dyads hospitalized in the Mother-Baby Unit of Bordeaux (UMB-Société Marcé Francophone - Database).

Method

Intake of psychotropic drugs during pregnancy was retrospectively evaluated in a sample of 187 women hospitalized with their baby. Neonatal adaptation of the newborns was evaluated through the APGAR score at 5 minutes of life. Univariate analyses were used for this exploratory study.

Results

APGAR scores of exposed newborns (87) were significantly lower, and specifically for newborns exposed to mood stabilizers and/or antipsychotics. Exposed children were more frequently hospitalized for neonatal cares. The duration of pregnancy was shorter for mothers treated with mood stabilizers and/or antipsychotics and/or benzodiazepines.

Conclusion

This preliminary exploratory study suggests, in spite of its limitations, that newborns whose mothers were hospitalized in post-partum and who used psychotropic medications during pregnancy presented with more neonatal health difficulties than those of untreated mothers.     

Comparing weight gain in the year prior to treatment for overweight and obese patients with and without binge eating disorder in primary care

Objective

To examine weight change trajectories among overweight and obese patients with binge eating disorder (BED) versus without (NBO) during the year prior to seeking treatment.

Methods

Participants were 97 (75 women, 22 men) overweight and obese patients recruited for the same weight-loss treatment in primary care; 26 (27%) met DSM-5 BED criteria. Participants were assessed with the Eating Disorder Examination and completed self-report questionnaires about their weight histories and the Beck Depression Inventory-II.

Results

Participants' self-reported current weight and measured current weight were significantly correlated and did not statistically differ. Reported weight changes during the year prior to seeking treatment differed significantly by group: BED patients gained an average of 18.3 lb (8.2 kg) whereas NBO patients gained an average of 1.5 lb (0.7 kg). Among BED patients, but not NBO, weight change during the prior year was positively correlated with greater eating-disorder psychopathology, binge-eating frequency, frequency of overeating at lunch and dinner, and depression scores. For the overall group, BED status and binge-eating frequency each made independent significant contributions to predicting weight change in the past year.

Conclusion

Findings suggest BED patients are gaining considerably more weight during the year prior to treatment than NBO patients. BED treatment may interrupt a steep weight gain trajectory and prevent further weight gain for BED patients suggesting need for early intervention. Primary care physicians should screen for BED when overweight and obese patients present with rapid weight gain.     

Association of change in depression and anxiety symptoms with functional outcomes in pulmonary rehabilitation patients

Objective

Pulmonary rehabilitation (PR) has emerged over the last decade as an essential component of an integrated approach to managing patients with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). We sought to examine how depression and anxiety symptom changes relate to disease-specific quality of life outcomes following PR.

Methods

We performed a cohort study of 81 patients with COPD who completed PR at a Veterans Administration Medical Center. Pulmonary rehabilitation consisted of supervised exercise training and education twice weekly for 8 weeks. Beck Depression and Anxiety Inventories (BDI and BAI) assessed symptom burden at baseline and completion of PR. We measured change in disease-specific quality of life using the dyspnea, mastery, emotion and fatigue domains of the Chronic Respiratory Questionnaire Self-Reported (CRQ-SR) from baseline to completion of PR.

Results

Participants were 69.8±9.1 years old and all male. Forced expiratory volume in 1 s (FEV1) was 1.23±0.39 L. The CRQ-SR scores improved significantly: dyspnea (P<.0001), mastery (P=.015) and fatigue (P=.017). The BDI scores improved significantly (13.1±10.5 to 10.8±9.9, P=.003; BAI: 13.1±10.1 to 12.1±11.7). Multivariate regression models controlling for age, FEV1, depression treatment and anxiety treatment showed that improvement in depressive symptoms were associated with improvement in fatigue (P=.003), emotion (P=.003) and mastery (P=.01). Anxiety symptom change was not significantly associated with change in disease-specific quality of life domains.

Conclusion

Addressing anxiety symptoms in PR patients may be indicated because disease-specific quality of life improvement appears to be associated with mood.     

Clinical significance of lifetime panic disorder in the course of bipolar disorder type I

Objectives

The aim of the study was to analyze the impact of lifetime panic disorder (PD) diagnosis in a sample of patients with bipolar disorder type I (BPI), evaluating clinical and demographic variables.

Methods

Ninety-five outpatients from the Bipolar Disorder Research Program at the Institute of Psychiatry of the University of Sao Paulo Medical School were enrolled. Twenty-seven BPI patients with PD were compared to 68 BPI patients without any anxiety disorders regarding clinical and demographic variables.

Results

Compared to BPI patients without any anxiety disorders, patients with BPI + PD presented significantly higher number of mood episodes (18.9 ± 13.8 vs 8.5 ± 7.8; P < .001), depressive episodes (10.8 ± 8.2 vs 4.6 ± 4.8; P = .001), and manic episodes (7.4 ± 7.3 vs 3.6 ± 3.6; P = .008). Patients with BPI + PD had more frequently a depressive episode as their first one compared to BPI patients without anxiety disorders (94.1% vs 57.5%; P = .011). Patients with BPI + PD had more comorbidity with lifetime diagnosis of drug abuse or dependence (33.3% vs 8.8%; P = .010) and eating disorders (29.6% vs 6.0%; P = .004).

Conclusions

The higher number of mood episodes in general presented by patients with BPI + PD when compared with BPI patients without any anxiety disorders, along with the higher frequencies of drug misuse and eating disorders, indicates that PD comorbidity is associated with a poorer course and outcome of BPI. The higher frequency of depression as the onset mood episode and the higher number of manic episodes in the group with PD may have important treatment implications and should be further investigated.     

Neurocognitive Functioning in Overweight and Obese Patients With Bipolar Disorder: Data From the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

Objective

Obesity is frequent in people with bipolar I disorder (BD I) and has a major impact on the course of the illness. Although obesity negatively influences cognitive function in patients with BD, its impact in the early phase of the disorder is unknown. We investigated the impact of overweight and obesity on cognitive functioning in clinically stable patients with BD recently recovered from their first manic episode.

Method:

Sixty-five patients with BD (25 overweight or obese and 40 normal weight) recently remitted from a first episode of mania and 37 age- and sex-matched healthy control subjects (9 overweight or obese and 28 normal weight) were included in this analysis from the Systematic Treatment Optimization Program for Early Mania (commonly referred to as STOP-EM). All subjects had their cognitive function assessed using a standard neurocognitive battery. We compared cognitive function between normal weight patients, overweight–obese patients, and normal weight healthy control subjects.

Results:

There was a negative affect of BD diagnosis on the domains of attention, verbal memory, nonverbal memory, working memory, and executive function, but we were unable to find an additional effect of weight on cognitive functioning in patients. There was a trend for a negative correlation between body mass index and nonverbal memory in the patient group.

Conclusions:

These data suggest that overweight–obesity does not negatively influence cognitive function early in the course of BD. Given that there is evidence for a negative impact of obesity later in the course of illness, there may be an opportunity to address obesity early in the course of BD.     

Zonisamide produces weight loss in psychotropic drug-treated psychiatric outpatients

This study examined the long-term effectiveness and tolerability of zonisamide for weight control in psychiatric outpatients using various psychotropic medications. We conducted a systematic chart review of 82 psychiatric outpatients with unwanted weight gain after the introduction of psychotropic drugs between January 2008 and September 2009 at Korea University Ansan Hospital. The primary outcome measure was the effect of zonisamide on body mass index (BMI). Additional outcome measures included safety and tolerability as assessed by the clinical global impression-severity of illness scale (CGI-S) and discontinuation rate. The mean final dose of zonisamide was 124.6 ± 53.4 mg/day and ranged from 50 mg/day to 300 mg/day. The mean BMI reduction was 0.8 ± 1.7 kg/m² and ranged from − 2.9 kg/m² to 4.7 kg/m² (p < 0.001). We also observed a significant reduction in CGI-S scores from the baseline (3.8 ± 0.9) to the endpoint (3.3 ± 0.8; p < 0.001). Twelve patients (14.6%) discontinued their zonisamide treatment due to its side effects. Patients treated with zonisamide showed significant weight loss. Furthermore, its treatment was generally safe and well tolerated with few negative effects on patients' overall psychiatric symptoms. Additional research is required to confirm these results and to investigate whether patients have rebound weight gains after discontinuing zonisamide.     

A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis

Background

We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis.

Methods

Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n = 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n = 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n = 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n = 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups.

Results

Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups.

Conclusions

Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS.     

Morphology of the subgenual prefrontal cortex in pediatric bipolar disorder

Objectives

The subgenual prefrontal cortex (SGPFC) is an important brain region involved in emotional regulation and reward mechanisms. Volumetric abnormalities in this region have been identified in adults with bipolar disorder but thus far not in pediatric cases. We examined the volume of this brain region in subjects with pediatric bipolar disorder (PBD) and compared them to healthy controls.

Methods

Fifty one children and adolescents (mean age ± SD; 13.2 ± 2.9 y) with DSM-IV PBD and 41 (mean age ± SD; 13.7 ± 2.7 y) healthy comparison subjects (HC) underwent 1.5 T structural magnetic resonance imaging (MRI) brain scans. We traced the SGPFC manually and compared SGPFC gray matter volumes using analysis of covariance with age, gender, and intracranial volume as covariates. We also examined the relationship of family history of affective disorders and medication status to SGPFC volumes.

Results

SGPFC volumes were not significantly different in PBD and HC subjects. However, exploratory analysis showed PBD subjects who had one or more first degree relatives with mood disorders (n = 33) had significantly smaller left hemisphere SGPFC compared to HC (p = 0.03 Sidak corrected). Current usage of a mood stabilizer was significantly associated with larger right SGPFC volume in PBD (F = 4.82, df = 1/41, p = 0.03).

Conclusion

Subjects with PBD and a close family history of mood disorders may have smaller left SGPFC volumes than HC. Mood stabilizing medication may also impact SGPFC size and could have masked more subtle abnormalities overall.     

The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet Disease and their association with thrombosis

Objective

To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis.

Methods

Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls.

Results

Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49 ± 8.88 µg/ml vs. 26.76 ± 11.57 µg/ml, p < 0.0001) and significantly higher levels of TM (3.26 ± 1.85 ng/ml vs. 2.6 ± 0.69 ng/ml, p = 0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p > 0.05). Despite a tendency to positive correlation (r = 0.37, p = 0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r = -0.51, p < 0.0001) between these two parameters in BD patients.

Conclusion

The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction.     

Activated protein C plasma levels in the fasting and postprandial states among patients with previous unprovoked venous thromboembolism

Introduction

The protein C anticoagulant system is of major importance in the regulation of thrombotic risk, but it is not known whether low plasma levels of activated protein C (APC) in vivo reflect a compromised anticoagulant situation with increased thrombotic risk. Previous studies have reported low, normal or increased plasma APC levels in unselected patients with venous thromboembolism (VTE).

Materials and methods

We performed a population-based, case-control study in patients with a previous history of unprovoked VTE and subjected the participants to a standard fat tolerance test (1 g fat/kg body weight) in order to promote physiological coagulation activation.

Results

VTE patients had higher BMI (28.3 ± 4.4 kg/m² versus 26.3 ± 3.9 kg/m², p = 0.045) and greater waist circumference (98.2 ± 12.5 cm versus 93.4 ± 13.4 cm, p = 0.041) than age and sex matched controls. APC levels were equal in fasting plasma (3.00 ± 0.74 ng/ml and 2.99 ± 0.60 ng/ml, p = 0.66) but higher in postprandial plasma (3.18 ± 0.57 ng/ml and 2.81 ± 0.38 ng/ml, p = 0.008) collected from VTE patients and controls, respectively. Endogenous thrombin generation in plasma following a standardized meal, assessed by thrombin-antithrombin complex (TAT), increased similarly in both groups, whereas APC increased only among the VTE patients during the postprandial state. Plasma levels of APC increased linearly with TAT in the postprandial state (p for linear trend = 0.012).

Conclusions

Our findings fail to support the hypothesis that low APC levels are linked to increased thrombotic risk in unprovoked VTE, and they suggest that plasma APC is a biomarker of thrombin generation.     

Different effects of enoxaparin and unfractionated heparin on some thrombogenesis markers during hemodialysis: a cross-over study

Background

Unfractionated heparin (UFH) and low molecular weight heparin constitute fundamental anticoagulants during hemodialysis (HD). We aimed to investigate the effect of UFH and enoxaparin on plasma levels of prothrombin fragment 1 + 2 (PF 1 + 2) and thrombin/antithrombin complex (TAT) as markers of intravascular thrombogenesis during HD.

Methods

We enrolled 22 chronic HD patients, who were randomly assigned to either iv enoxaparin (n = 11) or UFH (n = 11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. Plasma levels of PF 1 + 2 and TAT were measured by immunoassay at the start, at 10 and 180 min of HD session after each period of evaluation.

Results

The baseline PF 1 + 2 and TAT levels were comparable under enoxaparin and UFH treatment. PF 1 + 2 significantly decreased during both UFH (χ² ANOVA = 9.82, P = 0.007) and enoxaparin (χ² ANOVA = 29.40, P < 10^− 6) anticoagulated HD, while over-HD TAT levels changes differed depending on the type of heparin. The switch from enoxaparin to UFH treatment was connected with a significantly higher PF 1 + 2 after 10 and 180 min as well as higher TAT concentration after 180 min of HD. Only during enoxaparin anticoagulated HD 34% PF 1 + 2 decrease and TAT levels after 180 min of HD was closely associated with heparin dosage.

Conclusion

Single bolus of enoxaparin ensures efficient and convenient anti-thrombotic protection during HD procedure. Enoxaparin mean dose of 0.67 mg/kg, which is generally lower than manufacturer's instructions, can be recommended for over-dialytic regular use.     

The effects of repetitive transcranial magnetic stimulation on eating behaviors and body weight in obesity: A randomized controlled study

Background

Although some studies have reported significant reductions in food cravings following repetitive transcranial magnetic stimulation (rTMS), none have examined changes in body weight.

A psycho-genetic study of associations between the symptoms of binge eating disorder and those of attention deficit (hyperactivity) disorder

Objective

Some recent studies have reported intriguingly strong correlations between ADHD and obesity. This study examined whether ADHD symptoms were more pronounced in adults with symptoms of binge eating disorder (BE) than in their non-binging obese counterparts, and whether the links were stronger with inattentive vs impulsive/hyperactive symptoms. We also assessed the role of the dopamine D3 receptor in ADHD symptoms since the DRD3 gene has been associated with impulsivity and drug addiction - both relevant features of ADHD.

Methods

A case (BE: n = 60) double-control (normal weight: n = 61 and obese: n = 60) design was employed. Assessments of both childhood and adults ADHD symptoms were made, as well as genotyping of seven markers of DRD3 including the functional Ser9Gly polymorphism.

Results

Three DRD3 genotypes, including Ser/Ser, had significantly elevated scores on the hyperactive/impulsive symptom scale. In turn, the four ADHD symptom scales were all significantly elevated in the BE and obese groups, who did not differ from each other, compared to those with normal weight.

Conclusions

Results indicated a role for the D3 receptor in the manifestation of the hyperactive/impulsive symptoms of ADHD, and that symptoms of ADHD are significantly, but not differentially, elevated in obese adults with and without binge eating. Our findings suggest that ADHD screening in adults seeking treatment for obesity, including those with BE, may be warranted as methods used to treat ADHD may help some to better manage overeating and other factors contributing to weight gain.     

Shared impairment in associative learning in schizophrenia and bipolar disorder

Background

Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).

Methods

Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.

Results

Learning curves (performance = 1−e^−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.

Conclusions

Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission.