N. Lackner

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

Tryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report.

Individuals with bipolar disorder (BD) are disproportionately affected by symptoms of being overweight and metabolic syndrome when compared to the general population. The pertinence of this observation is underscored by observations that excess weight is associated with a more complex illness presentation, course, and outcome in BD. We present the first preliminary report of our BIPFAT study, which explored shared hypothesized pathophysiological pathways between being overweight and having BD.

Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals

Objectives. Overweight/obesity has been implicated to play a role in cognitive deficits in bipolar disorder (BD). This study aims to identify the relationship between body fat distribution and different domains of cognition in BD during euthymia. Methods. A sample of 100 euthymic individuals with BD was measured with a cognitive test battery (i.e., Trail Making Test-A-B/TM-A/B, d2 Test of Attention, Stroop test, California Verbal Learning Test/CVLT) and an anthropometric measures set (body mass index, waist circumference, hip circumference, waist-to-hip-ratio, waist-to-height-ratio, and lipometry). Patient data were compared with a healthy control group (n = 64). Results. Results show that overweight patients with BD exhibit lower performance in the TMT-A/B as well as in the free recall performance of the CVLT compared to normal-weight patients with BD and controls. In bipolar individuals, (abdominal) obesity was significantly associated with a poor cognitive performance. In bipolar females, associations with measures of verbal learning and memory were found; in bipolar males, associations with poor performance in the TMT-A/B and in the Stroop interference task were demonstrated. In controls, no associations were found. Conclusions. There are several possible pathways moderating the association between obesity and cognition in BD. Anthropometric and lipometry data underline the substantial mediating impact of body fat distribution on cognition in BD.

Differences in Big Five Personality Traits Between Alcohol and Polydrug Abusers: Implications for Treatment in the Therapeutic Community

This pilot study examines personality characteristics using the Five Factor Model combined with measures of Sensation Seeking and religious/spiritual well-being in two Austrian samples of substance abusers. Sixty-three male addicts (33 polydrug dependents, 30 alcohol dependents) treated in a therapeutic community setting were tested with the Neo Personality Inventory Revised Version, the Sensation Seeking Scale, and the Multidimensional Inventory for Religious/Spiritual Well-Being. Results show significant personality differences between alcohol and polydrug abusers. Whereas higher levels of Neuroticism and lower levels of Openness to experience were found in both substance dependents groups, low levels of Conscientiousness and low levels of Agreeableness were merely shown in polydrug abusers. Furthermore, they exhibit less religious/spiritual well-being and high Sensation Seeking. Thus, the results seem to highlight a link between polydrug dependence and problematic personality structure. Findings have implications for understanding differences between various substance abusers and for novel treatment opportunities in the therapeutic community setting.

Weight cycling in bipolar disorder

BACKGROUND An association between excess weight and/or weight fluctuations and cardiovascular morbidity and mortality is amply documented. Individuals with bipolar disorder (BD) are differentially affected by overweight/obesity, chaotic eating patterns (e.g., binge eating), as well as cardiovascular morbidity and mortality. Weight cycling (WCYC) is defined as a pattern of repetitive weight loss and gain. METHODS We sought to determine the relationship between course of illness and BD and WCYC retrospectively as well whether these co-occurring phenotypes identify a biologically distinct subpopulation on the basis of having a unique inflammatory biomarker/biosignature profile. Sociodemographic, clinical, and inflammatory markers were gathered from a well-characterized cohort of actual euthymic adults with BD (n=101) and a healthy control group (n=48). RESULTS Individuals with BD with a history of WCYC were provided evidence of a greater frequency of prior episodes (i.e., both manic and depressed), as well as of significantly higher levels of circulating IL-6 concentrations when compared to non-WCYC individuals with BD. The association persisted after adjusting for relevant covariates (e.g., BMI, age, number of prior episodes). LIMITATIONS Include the small control group, differing medication status and that all data relies on personal information. Nevertheless we tried to verify all data as far as clinical disclosure was available. CONCLUSION The results of this study indicate that adults with BD excessive in weight are not only more susceptible to a relapse-prone course of illness, but also are more likely to present with WCYC. The finding of elevated pro-inflammatory cytokines in this subpopulation may identify a separate subpopulation with greater susceptibility to cardiovascular disease. The overarching aim of personalized treatment and preventive strategies in BD begins with appropriate, empirically supported patient stratification. Our results provide preliminary support for stratifying BD cardiovascular risk on the basis of anthropometrics and WCYC.

Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals.

Abstract Overweight and obesity differentially affect bipolar disorder (BD) and are associated with a poorer prognosis. Herein, we sought to evaluate body fat distribution in a well-characterized BD sample. Anthropometric measures (i.e., body mass index, waist-to-hip ratio, waist-to-height ratio, waist circumference, hip circumference, and lipometry) of 100 BD individuals were compared with data of 57 matched mentally healthy controls. Additionally, fasting serum parameters including metabolic parameters and monoamines were analyzed. Findings indicate that similar to US BD cohorts, Austrian patients exhibit an increased central body fat accumulation (i.e., higher subcutaneous adipose tissue at upper abdomen) accompanying with the harmful IDF-defined metabolic syndrome. In addition, positive associations between epinephrine as well as staging and fat parameters were detected.

Motivational processing of food cues in anorexia nervosa: a pilot study

Current literature suggests an increased attentional bias toward food stimuli in eating-disordered individuals compared to healthy controls. In line with these research efforts, the present study aims to investigate the processing of food stimuli (enriched by emotional stimuli) between patients diagnosed for anorexia nervosa (AN) and healthy controls by means of electroencephalography. Twenty-two female adolescents (eleven AN patients vs. eleven healthy controls) were investigated. Positive event-related potentials “P300” and “late positive potential” (LPP) reflecting attentional processing (caused by motivationally relevant stimuli) were investigated during passive viewing of the food cue picture stream. This method was used for the first time in a sample of individuals with AN. As a main result, AN patients exhibited a higher amount of attentional bias in P300 and LPP, while watching food stimuli. Moreover, AN patients rated food stimuli as less pleasant. For a conclusion, there is substantial evidence pointing to an abnormal attentional brain reactivity to food pictures in AN. Therefore, food stimuli seem to be more motivationally relevant for AN patients than for healthy controls. By broadening existing knowledge, these findings might bear some implications for the treatment for AN. However, further research is recommended in order to confirm the results coming from rather limited data.

EEG neurofeedback effects in the treatment of adolescent anorexia nervosa

ABSTRACT A pre-post design including 22 females was used to evaluate the effectiveness of neurofeedback in the treatment of adolescent anorexia nervosa. Resting EEG measures and a psychological test-battery assessing eating behavior traits, clinical symptoms, emotionality, and mood were obtained. While both the experimental (n = 10) and control group (n = 12) received their usual maintenance treatment, the experimental group received 10 sessions of individual alpha frequency training over a period of 5 weeks as additional treatment. Significant training effects were shown in eating behavior traits, emotion regulation, and in relative theta power in the eyes closed condition. Although the results are limited due to the small sample size, these are the first empirical data demonstrating the benefits of neurofeedback as a treatment adjunct in individuals with anorexia nervosa.

The Effectiveness of Visual Short-Time Neurofeedback on Brain Activity and Clinical Characteristics in Alcohol Use Disorders Practical Issues and Results

The present study was carried out to examine the efficacy of alpha/theta neurofeedback (NF) with a new visual paradigm in a cohort of alcohol use disordered (AUD) patients (n = 25) treated in an Austrian therapeutic community center. The experimental study design focused on changes in absolute and relative resting EEG band power as well as in clinical variables, including depression (Beck Depresion Inventory [BDI-V]), psychiatric symptoms (Brief Symptom Inventory [BSI], coping (Freiburg Questionnaire on Coping with Illness [FKV-lis]), psychotherapy motivation (Therapy Motivation Questionnaire [FPTM-23]), sense of coherence (Sense of Coherence Scale [SOC-13]), posttraumatic growth (Posttraumatic Growth Inventory [PPR]), and alcohol cravings (Alcohol Craving Questionnaire [ACQ]). For measuring training effects, participants were randomly allocated to 2 groups: an experimental group (EG, n = 13) and a control group (CG, n = 12). Patients in EG received 12 sessions of visual NF training over a period of 6 weeks to enhance alpha (8-12 Hz) and theta (4-7 Hz) frequency band power in addition to the standard treatment program of the rehabilitation center. Participants in CG received no additional NF intervention. The multivariate analysis of covariance (MANCOVA) showed a change by trend in absolute alpha and theta power in the EG. Even though no MANCOVA effects were found in the clinical scales, AUD patients reported increasing control of their brain activity during the course of NF. However, changes in several clinical scales (BDI-V, BSI, FKV-lis, PPR) from pre- to posttest were observed only in the EG contrary to the CG. The findings of this pilot study provide first evidence for the practicality and effectiveness of visual short-term NF as an additive intervention in the therapeutic community.

Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL.

Abstract Objectives: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. Methods: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5′ region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing. Analysis of covariances considering the covariates age, body mass index, sex, smoking, lithium and anticonvulsant intake were performed to test methylation differences between BD and controls. Results: Methylation at cg05733463 of ARNTL was significantly higher in BD than in controls (F(1,209) = 44.500, P < .001). In contrast, methylation was significantly lower in BD at PS2_POS1 compared to controls (F(1,128) = 5.787, P = .018) and by trend at PS2_POS2 (F(1,128) = 3.033, P = .084) and POS7 (F(1,34) = 3.425, P = .073). Conclusions: Methylation of ARNTL differed significantly between BD and controls. Thus, our study suggests that altered epigenetic regulation of ARNTL might provide a mechanistic basis for better understanding circadian rhythms and mood swings in BD.