State-related alterations of gene expression in bipolar disorder : a systematic review

Objective:  Alterations in gene expression in bipolar disorder have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related.

Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications.

Results:  A total of 17 studies were included, comprising 565 patients and 418 control individuals. Six studies evaluated intraindividual alterations in gene expression across mood states. Two of five studies found evidence of intraindividual alterations in gene expression between a depressed state and a euthymic state. No studies evaluated intraindividual differences in gene expression between a manic state and a euthymic state, while only one case study evaluated differences between a manic state and a depressed state, finding altered expression in seven genes. No study investigated intraindividual variations in gene expression between a euthymic state and multiple states of various polarities (depressive, manic, hypomanic). Intraindividual alterations in expression of the same genes were not investigated across studies. Only one gene (the brain-derived neurotrophic factor gene; BDNF) was investigated across multiple studies, showing no alteration between bipolar disorder patients and control individuals.

Conclusions:  There is evidence of some genes exhibiting state-related alterations in expression in bipolar disorder; however, this finding is limited by the lack of replication across studies. Further prospective studies are warranted, measuring gene expression in various affective phases, allowing for assessment of intraindividual differences.

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with ‘real-world’ treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.

Methods Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale – Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.

Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.

Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Cumulative morbidity and prognostic staging of illness in the systematic treatment enhancement program for Bipolar Disorder (STEP-BD)

Objective: Staging models may provide heuristic utility for intervention selection in psychiatry. Although a few proposals have been put forth, there is a need for empirical validation if they are to be adopted. Using data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we tested a previously elaborated hypothesis on the utility of using the number of previous episodes as a relevant prognostic variable for staging in bipolar disorder.

Methods: This report utilizes data from the multisite, prospective, open-label study ‘Standard Care Pathways’ and the subset of patients with acute depressive episodes who participated in the randomized trial of adjunctive antidepressant treatment. Outpatients meeting DSM-IV diagnostic criteria for bipolar disorder (n = 3345) were included. For the randomized pathway, patients met criteria for an acute depressive episode (n = 376). The number of previous episodes was categorized as less than 5, 5–10 and more than 10. We used disability at baseline, number of days well in the first year and longitudinal scores of depressive and manic symptoms, quality of life and functioning as validators of models constructed a priori.

Results: Patients with multiple previous episodes had consistently poorer cross-sectional and prospective outcomes. Functioning and quality of life were worse, disability more common, and symptoms more chronic and severe. There was no significant effect for staging with regard to antidepressant response in the randomized trial.

Conclusions: These findings confirm that bipolar disorder can be staged with prognostic validity. Stages can be used to stratify subjects in clinical trials and develop specific treatments.

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

Aims

Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.
Methods

As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo.
Results

This study failed to find changes in cognitive function following treatment with NAC compared to placebo.
Conclusions

While an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.

Psychosocial predictors of eating disorder risk in overweight and obese treatment-seeking adolescents

This study explored eating disorder risk factors and possible psychosocial predictors of this risk in overweight and obese treatment-seeking adolescents. Prior to commencing treatment 108 overweight and obese adolescents aged 11 to 17 years (M = 14.31, SD = 1.57; 55% female) completed self-report measures of psychosocial factors. Females reported elevated levels of bulimic tendencies, body dissatisfaction, drive for thinness (p ≤ .001) and males reported elevated body dissatisfaction (p < .001). Age, sex and BMI-for-age z-score explained 15% (p < .001) of the variance in eating disorder risk and psychosocial predictors an additional 25%. Sex did not have a moderating effect on these relationships (p = .21). Among overweight and obese treatment-seeking adolescents, those experiencing lower self-esteem and elevated depression and anxiety symptomatology are at increased eating disorder risk. This highlights the need to consider psychosocial factors in preventing and treating overweight and obesity.

Perceptions of carer burden : differences between individuals with an eating disorder and their carer

Carer burden in eating disorders is considerable, but to date no research has examined carer burden from the perspective of the person with an eating disorder. The current brief report assessed carer burden with a short questionnaire, as perceived by 20 matched pairs of sufferers and their carers. Those with an eating disorder significantly underestimated the overall burden experienced by their carer, particularly in relation to nutritional difficulties and conflict within the family. Domains where carers and sufferers had high agreement may be useful in facilitating collaborative involvement between sufferers and carers in treatment, such as multi-family therapy.

Managing panic disorder in general practice

BACKGROUND: Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns.

OBJECTIVE: This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies.

DISCUSSION Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.

Managing panic disorder in general medical practice

Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns. This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies. Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.

Internet administration of three commonly used questionnaires in panic research : equivalence to paper administration in Australian and Swedish samples of people with panic disorder

This study assessed the degree of equivalence between paper and Internet administration of three measures of panic and agoraphobia-related cognition and behavior: Body Sensations Questionnaire (BSQ), Agoraphobic Cognitions Questionnaire (ACQ), and Mobility Inventory (MI). Participants were 110 people with panic disorder who had registered for an Internet-based treatment program in Sweden (n = 54) or Australia (n = 56). Participants were randomly assigned to complete the questionnaires via the differing administration formats in a counterbalanced order. Results showed broadly equivalent psychometric properties across administrations, with strong significant intraclass correlations between them, and comparable Cronbach's alpha coefficients. A significant mean difference between administration formats was found for the BSQ only. In contrast to previous research, Internet administration did not generate higher scores than paper administration. No effect was found for order of administration. The findings suggest that each questionnaire can be validly administered via the Internet and used with confidence.

A test of core assumptions of the catastrophic misinterpretation model of panic disorder

The catastrophic misinterpretation model of panic disorder proposes that spontaneous panic attacks are the result of misinterpretation of harmless autonomic arousal as precursors to physical (e.g. heart attack) or psychological (e.g. insanity) emergency. Mixed research findings to date have provided equivocal support. A modified form of the Body Sensations Interpretation Questionnaire was used to investigate core assumptions of the model amongst 38 people with panic disorder (PD), 20 with non-clinical panic, 21 with social anxiety disorder, and 34 non-anxious controls. The PD group gave more harm-related interpretations of ambiguous internal stimuli than all other groups only when anxiety-related responses (e.g. “I'm going to panic”) were scored as harm, however there was no evidence that anxiety-related interpretations were masking perceived catastrophic physical or psychological outcomes. Despite this, people with PD rated harm and anxiety outcomes as more negative than non-anxious controls. Results failed to unequivocally support core assumptions of the model.

Commentary : Fatty acids, breastfeeding and Autism Spectrum Disorder

Fatty acid deficiencies are linked to Autism Spectrum Disorder. This commentary discusses the protective role of breastfeeding and the urgency of research into the human infant's intake of colostrum to prevent fatty acid deficiency.

Discriminant validity of the sensory profile in Australian children with autism spectrum disorder

Objective. The discriminant validity of the Sensory Profile was evaluated by comparing the sensory processing scores of Australian children, 5 to 8 years of age, diagnosed with autism spectrum disorder (ASD) to a control group of children with typical development matched for age and gender. Method. Twenty-six parents of children with ASD and 26 parents of typically developing children without ASD completed the Sensory Profile. Sensory Profile category, factor, and quadrant scores were compared using multivariate analysis to investigate if there were differences between the two groups. Results. The results indicated that the children with ASD had significantly lower sensory processing scores on all fourteen categories, eight out of nine factors, and all four quadrants of the Sensory Profile. Conclusion. The results also provide evidence of discriminant validity of Sensory Profile scores between children with ASD and children with typical development. In addition, the study findings indicate that the Sensory Profile can be used with confidence in cross-cultural contexts, such as Australia.