The bipolar depression rating scale (BDRS) : its development, validation and utility

Objectives: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression.

Methods: An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18–65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).

Results: The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters.

Conclusions: This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.

Scale matters : the need for a Bipolar Depression Rating Scale (BDRS)

Objective: To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer-rated scale tailored to bipolar depression.

Method: Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors.

Results: Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self-report and observer-rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression.

Conclusion: The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.

A novel bipolar time-spread echo hiding based watermarking method for stereo audio signals

In this paper, a novel bipolar time-spread (TS) echo hiding based watermarking method is proposed for stereo audio signals, to overcome the low robustness problem in the traditional TS echo hiding method. At the embedding, echo signals with opposite polarities are added to both channels of the host audio signal. This improves the imperceptibility of the watermarking scheme, since added watermarks have similar effects in both channels. Then decoding part is developed, in order to improve the robustness of the watermarking scheme against common attacks. Since these novel embedding and decoding methods utilize the advantage of two channels in stereo audio signals, it significantly reduces the interference of host signal at watermark extraction which is the main reason for error detection in the traditional TS echo hiding based watermarking under closed-loop attack. The effectiveness of the proposed watermarking scheme is theoretically analyzed and verified by simulations under common attacks. The proposed echo hiding method outperforms conventional TS echo hiding based watermarking when their perceptual qualities are similar.

Obesity is associated with previous suicide attempts in bipolar disorder

Objective: There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder.

Methods: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese.

Results: Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s).

Conclusion: Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.

Diet quality in bipolar disorder in a population-based sample of women

Background : Recent epidemiological evidence has indicated a role for diet quality in unipolar depressive illness. This study examined the association between diet quality and bipolar disorder (BD) in an epidemiological cohort of randomly selected, population-based women aged 20–93 years.

Methods : An a priori diet quality score was derived from food frequency questionnaire data, a factor analysis identified habitual dietary patterns and glycemic load was assessed. Mental health was assessed using the SCID-I/NP.

Results : BD was identified in 23 women and there were 691 participants with no history of psychopathology. Compared to those with no psychopathology, those with BD had a higher glycemic load (p = 0.06) and higher scores on a ‘western’ dietary factor (p = 0.03) and the ‘modern’ dietary factor (p = 0.02). For each standard deviation increase in a ‘western’ and ‘modern’ dietary pattern and glycemic load, the odds ratios for BD were increased (‘western’ OR = 1.88, 95% CI 1.33–2.65; ‘modern’ OR = 1.72, 95% CI 1.14–2.39; GL OR = 1.56, 95% CI 1.13–2.14). Conversely, a ‘traditional’ dietary pattern was associated with reduced odds for BD (OR = 0.53 95% CI 0.32–0.89) after adjustments for overall energy intake.

Limitations : The small sample size did not allow for multivariate analyses and the cross-sectional study design precludes any determinations regarding the direction of the relationships between diet quality and BD.

Conclusion : These data are largely concordant with results from dietary studies in unipolar depression. However, clinical recommendations cannot be made until the direction of the relationship between diet quality and BD is determined. Longitudinal studies are warranted.

Randomized placebo controlled trials of n-acetyl cysteine as adjunct therapy for schizophrenia and bipolar disorder

Glutathione is the principal antioxidant of the brain. There is evidence of oxidative stress, lowered brain glutathione and genetic linkage involve glutathione metabolic genes in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a safe, orally bioavailable, precursor of glutathione. NAC has been shown to reverse animal models of oxidative stress, and raises brain glutathione levels.

N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice.

The tripeptide, glutathione (glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.