Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome.

Mitochondrial diseases represent a spectrum of disorders caused by impaired mitochondrial function, ranging in severity from mortality during infancy to progressive adult-onset disease. Mitochondrial dysfunction is also recognized as a molecular hallmark of the biological ageing process. Rapamycin, a drug that increases lifespan and health during normative ageing, also increases survival and reduces neurological symptoms in a mouse model of the severe mitochondrial disease Leigh syndrome. The Ndufs4 knockout (Ndufs4-/-) mouse lacks the complex I subunit NDUFS4 and shows rapid onset and progression of neurodegeneration mimicking patients with Leigh syndrome. Here we show that another drug that extends lifespan and delays normative ageing in mice, acarbose, also suppresses symptoms of disease and improves survival of Ndufs4-/- mice. Unlike rapamycin, acarbose rescues disease phenotypes independently of inhibition of the mechanistic target of rapamycin. Furthermore, rapamycin and acarbose have additive effects in delaying neurological symptoms and increasing maximum lifespan in Ndufs4-/- mice. We find that acarbose remodels the intestinal microbiome and alters the production of short-chain fatty acids. Supplementation with tributyrin, a source of butyric acid, recapitulates some effects of acarbose on lifespan and disease progression, while depletion of the endogenous microbiome in Ndufs4-/- mice appears to fully recapitulate the effects of acarbose on healthspan and lifespan in these animals. To our knowledge, this study provides the first evidence that alteration of the gut microbiome plays a significant role in severe mitochondrial disease and provides further support for the model that biological ageing and severe mitochondrial disorders share underlying common mechanisms.

Measuring the effectiveness of using rangers to deliver a behavior change campaign on sustainable palm oil in a UK zoo.

A fundamental objective of modern zoos is promoting pro-environmental behaviors. This study experimentally assessed the contribution of zoo rangers (staff employed to engage visitors) in delivering a behavior change campaign promoting sustainable palm oil use. The campaign was delivered in a dedicated area in a walk-through animal exhibit, with rangers either "present" or "absent" in the campaign space. Questionnaires assessing awareness, knowledge, and purchasing intentions were completed by 1032 visitors. Two analyses were conducted: (1) comparing the impact of ranger presence versus absence (to assess the overall impact of having rangers present regardless of whether they talked to visitors) and (2) comparing the impact of talking to a ranger against demographically matched individuals visiting when rangers were absent (to assess the specific impact of talking to a ranger). Visitors who talked to rangers were more aware of palm oil, had more knowledge, and greater intentions of purchasing sustainable palm oil. However, as only one-quarter of visitors talked to a ranger, fewer differences were found comparing ranger presence versus absence. These findings suggest that rangers can be instrumental in communicating complex conservation issues and delivering zoo-based behavior change campaigns, but their impact is limited by low engagement rates.

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

French-fried potato consumption and energy balance: a randomized controlled trial.

BACKGROUND: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed. OBJECTIVES: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption. METHODS: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries (potato group), or 3) French fries with herb/spices mix (potato + herb/spices group). Baseline and 30-d FM were measured by DXA (primary outcome), with secondary outcomes including body weight and carbohydrate metabolism markers [glycated hemoglobin (HbA1c), fasting blood glucose and insulin, HOMA-IR)]. A subset of 5 participants/group participated in a postprandial meal-based tolerance test. RESULTS: A total of 180 participants were randomly assigned [gender: 67.8% female; mean ± SD age: 30.4 ± 8.7 y; BMI (in kg/m2): 26.1 ± 4.2; and weight: 75.6 ± 15.4 kg], with 12 dropouts and 3 terminations. No significantly different FM changes were observed between almond and potato consumption [combined ± herb/spices; mean ± SE almond: 230.87 ± 114.01 g; potato: 123.73 ± 86.09 g; P = 0.443], fasting glucose (P = 0.985), insulin (P = 0.082), HOMA-IR (P = 0.080), or HbA1c (P = 0.269). Body weight change was not significantly different in the potato groups combined compared with the almond group (P = 0.116), but was significantly different among the 3 groups (P = 0.014; almond: 0.49 ± 0.20 kg; potato: -0.24 ± 0.20 kg; potato + herb/spices: 0.47 ± 0.21 kg). In meal tests, significantly lower post-prandial glucose and insulin responses to almonds compared with potatoes were observed (P = 0.046, P = 0.006, respectively), with potato + herb/spices having intermediate effects. CONCLUSION: There were no significant differences in FM or in glucoregulatory biomarkers after 30 d of potato consumption compared with almonds. Results do not support a causal relation between increased French fried potato consumption and the negative health outcomes studied. This trial was registered at clinicaltrials.gov as NCT03518515.

Exogenous Dietary Ketone Ester Decreases Body Weight and Adiposity in Mice Housed at Thermoneutrality.

OBJECTIVE: The aim of this study was to examine the effects of a ketone ester (KE)-supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished. METHODS: Thirty-two 10-week-old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per group): 30% KE diet + 23 °C (KE23), control (CON) diet + 23 °C (CON23), 30% KE diet + 30 °C (KE30), or CON diet + 30 °C (CON30). CON mice were pair-fed to the average intake of mice consuming the KE diet (ad libitum) for 8 weeks. Body composition and components of energy balance were measured at completion of the study. RESULTS: CON23 (mean ± SD, 26.0 ± 1.6 g) and CON30 (29.7 ± 1.4 g) mice weighed more than KE groups (P < 0.03 for both) and were also different from each other (CON23 vs. CON30, P < 0.01). However, KE23 (23.4 ± 2.7 g) and KE30 (23.1 ± 1.9 g) mice were not different in body weight. As expected, food intake at 30 °C (2.0 ± 0.3 g/d) was lower than at 23 °C (2.6 ± 0.3 g/d, P < 0.01). Diet did not influence resting and total EE, but mice housed at 30 °C had lower EE compared with mice at 23 °C (P < 0.01). CONCLUSIONS: Dietary KEs attenuate body weight gain at standard (23 °C) and thermoneutral (30 °C) housing temperatures, and this effect is not mediated by increased EE under these conditions.

Impact of vegetation selection on nitrogen and phosphorus processing in bioretention containers.

A year-long bioretention container study in Maryland, USA, measured the relationship between three plant species (Eutrochium dubium, Iris versicolor, and Juncus effusus) and N ( NO 3 - , NO 2 - , NH 4 + , total nitrogen [TN], total dissolved nitrogen [TDN], dissolved organic nitrogen, particulate organic nitrogen [PON]) and total phosphorus (TP) removal from synthetic stormwater. Statistically significant removal was only found for NO 3 - and TP. Plant-independent NO 3 - removal occurred 9 months after planting, and then changed to removal only by the least-densely planted Juncus treatment. Removal in higher-density Juncus plantings was suspected to be limited by preferential pathways created by high root density. Juncus' low-density NO 3 - removal success correlates with its high growth rate, root mass and length, and large biomass, matching previous literature. TP removal was plant-independent. Shoot harvesting of one plant of each species after 1 year would remove 0.61 g N. Of the plant species in this study, Juncus effusus is most highly recommended for bioretention for its nutrient removal dynamics and year-round green aesthetics. PRACTITIONER POINTS: Only the one-Juncus density treatment had significant NO 3 - removal. All Juncus treatments as well as non-Juncus treatments prevented the PON, TN, or TDN export seen in the No-plants control. TP removal was plant-independent. Juncus had the greatest biomass increase and biomass N. Shoots contain the majority of biomass N for each plant species. Juncus and Iris had high survivorship. Joe Pye had low survivorship. These, and all other study results, need field-scale verification.

Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection.

Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. It is known to have a biological role in oxidative stress, inflammation, and cell migration. There have been several reports demonstrating anti-infective properties targeting viruses, bacteria, and even the malarial parasite. We and others have previously described broad-spectrum antimicrobial and antibiofilm activities of cysteamine. Here, we go further to demonstrate redox-dependent mechanisms of action for the compound and how its antimicrobial effects are, at least in part, due to undermining bacterial defenses against oxidative and nitrosative challenges. We demonstrate the therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotics against a selection of priority antibiotic-resistant pathogens, including colistin (often considered an antibiotic of last resort), and we discuss how this endogenous antimicrobial component of innate immunity has a role in infectious disease that is beginning to be explored and is not yet fully understood.

Knowledge-Sharing Networks in Hunter-Gatherers and the Evolution of Cumulative Culture.

Humans possess the unique ability for cumulative culture [1, 2]. It has been argued that hunter-gatherer's complex social structure [3-9] has facilitated the evolution of cumulative culture by allowing information exchange among large pools of individuals [10-13]. However, empirical evidence for the interaction between social structure and cultural transmission is scant [14]. Here we examine the reported co-occurrence of plant uses between individuals in dyads (which we define as their "shared knowledge" of plant uses) in BaYaka Pygmies from Congo. We studied reported uses of 33 plants of 219 individuals from four camps. We show that (1) plant uses by BaYaka fall into three main domains: medicinal, foraging, and social norms/beliefs; (2) most medicinal plants have known bioactive properties, and some are positively associated with children's BMI, suggesting that their use is adaptive; (3) knowledge of medicinal plants is mainly shared between spouses and biological and affinal kin; and (4) knowledge of plant uses associated with foraging and social norms is shared more widely among campmates, regardless of relatedness, and is important for camp-wide activities that require cooperation. Our results show the interdependence between social structure and knowledge sharing. We propose that long-term pair bonds, affinal kin recognition, exogamy, and multi-locality create ties between unrelated families, facilitating the transmission of medicinal knowledge and its fitness implications. Additionally, multi-family camps with low inter-relatedness between camp members provide a framework for the exchange of functional information related to cooperative activities beyond the family unit, such as foraging and regulation of social life.

Pseudomonas aeruginosa antibiotic resistance in Australian cystic fibrosis centres.

BACKGROUND AND OBJECTIVE: In cystic fibrosis (CF), chronic Pseudomonas aeruginosa infection is associated with increased morbidity, antibiotic treatments and mortality. By linking Australian CF registry data with a national microbiological data set, we examined the association between where treatment was delivered, its intensity and P. aeruginosa antibiotic resistance. METHODS: Sputa were collected from paediatric and adult CF patients attending 18 Australian CF centres. P. aeruginosa antibiotic susceptibilities determined by local laboratories were correlated with clinical characteristics, treatment intensity and infection with strains commonly shared among Australian CF patients. Between-centre differences in treatment and antibiotic resistance were also compared. RESULTS: Large variations in antibiotic usage, maintenance treatment practices and multi-antibiotic resistant P. aeruginosa (MARPA) prevalence exist between Australian CF centres, although the overall proportions of MARPA isolates were similar in paediatric and adult centres (31% vs 35%, P = 0.29). Among paediatric centres, MARPA correlated with intravenous antibiotic usage and the Australian state where treatment was delivered, while azithromycin, reduced lung function and treating state predicted intravenous antibiotic usage. In adult centres, body mass index (BMI) and treating state were associated with MARPA, while intravenous antibiotic use was predicted by gender, BMI, dornase-alpha, azithromycin, lung function and treating state. In adults, P. aeruginosa strains AUST-01 and AUST-02 independently predicted intravenous antibiotic usage. CONCLUSION: Increased treatment intensity in paediatric centres and the Australian state where treatment was received are both associated with greater risk of MARPA, but not worse clinical outcomes.

Impact of paroxysmal sympathetic hyperactivity on nutrition management after brain injury: a case series.

OBJECTIVE: To review the nutritional requirements of all new inpatient brain injury admissions presenting with Paroxysmal Sympathetic Hyperactivity (PSH) in the rehabilitation setting. METHODS: RABIU is a 25-bed Regional facility in Northern Ireland which opened in 2006. All records of patients with a single episode non-progressive acquired brain injury admitted to RABIU from 2006 until the present were reviewed for evidence of PSH. Dietetic assessment and management was examined and recorded. RESULTS: Four patients with persisting paroxysmal sympathetic hyperactivity were identified. All patients displayed dystonia and posturing and had clinically important percentage weight loss. All had nutrition and/or hydration requirements markedly above their estimated requirement for slow weight gain, despite adjustment for brain injury. All four had posture-related complications of their dystonia and nutrition. CONCLUSION: Careful monitoring of nutrition, hydration and mineral supplementation is paramount in patients presenting with paroxysmal sympathetic hyperactivity after brain injury. It is argued that morbidity may be reduced by aggressive and expert nutrition management.

Multimorbidity and mental health: can psychiatry rise to the challenge?

Multimorbidity--the co-occurrence of two or more long-term conditions in an individual - is highly relevant to psychiatry. Changes to training and a more integrated model of psychiatric and physical healthcare are needed in the future if we are to improve the long-term health of our patients.

Effects of risperidone on energy balance in female C57BL/6J mice.

OBJECTIVE: To investigate the effect of risperidone on energy expenditure and weight gain in female C57BL/6J mice. DESIGN AND METHODS: Body weight and composition, food intake, energy expenditure, and activity were determined weekly. mRNA expression of uncoupling protein 1 in brown adipose tissue, orexin, and brain-derived neurotrophic factor in the hypothalamus were quantified using real-time PCR. RESULTS: Risperidone tended to induce a greater body weight gain (P = 0.052) and significantly higher food intake (P = 0.038) relative to the placebo-treated group. Risperidone-treated mice had a higher resting energy expenditure (P = 0.001) and total energy expenditure (TEE) (P = 0.005) than the placebo group. There were no effects of treatment, time, and treatment by time on non-resting (or activity-related) energy expenditure between groups. Risperidone-treated mice showed a significantly lesser locomotor activity than placebo-treated mice over 3 weeks (P < 0.001). Risperidone induced a higher UCP1 mRNA (P = 0.003) and a lower orexin mRNA (P = 0.001) than placebo. CONCLUSION: Risperidone-induced weight gain is associated with hyperphagia and a reduction in locomotor activity in C57BL/6J mice. Additionally, higher total and resting energy expenditure were accompanied by higher levels of UCP1 mRNA in BAT. The increased TEE could not offset the total intake of energy through risperidone-induced hyperphagia, therefore resulting in weight gain in female C57BL/6J mice.

Petroleum coke adsorption as a water management option for oil sands process-affected water.

Water is integral to both operational and environmental aspects of the oil sands industry. A water treatment option based on the use of petroleum coke (PC), a by-product of bitumen upgrading, was examined as an opportunity to reduce site oil sands process-affected water (OSPW) inventories and net raw water demand. Changes in OSPW quality when treated with PC included increments in pH levels and concentrations of vanadium, molybdenum, and sulphate. Constituents that decreased in concentration after PC adsorption included total acid-extractable organics (TAO), bicarbonate, calcium, barium, magnesium, and strontium. Changes in naphthenic acids (NAs) speciation were observed after PC adsorption. A battery of bioassays was used to measure the OSPW toxicity. The results indicated that untreated OSPW was toxic towards Vibrio fischeri and rainbow trout. However, OSPW treated with PC at appropriate dosages was not acutely toxic towards these test organisms. Removal of TAO was found to be an adsorption process, fitting the Langmuir and Langmuir-Freundlich isotherm models. For TAO concentrations of 60 mg/L, adsorption capacities ranged between 0.1 and 0.46 mg/g. This study demonstrates that freshly produced PC from fluid cokers provides an effective treatment of OSPW in terms of key constituents' removal and toxicity reduction.

Commercial naphthenic acids and the organic fraction of oil sands process water induce different effects on pro-inflammatory gene expression and macrophage phagocytosis in mice.

Naphthenic acids (NAs) are believed to be the major toxic component of oil sands process water (OSPW). Different OSPW preparations have distinct NA compositions, and additional organics, that differ from the commercial NAs (C-NAs) often used for toxicology studies. To evaluate whether C-NAs are an adequate model to study OSPW toxicity in complex organisms, we compared the effects of C-NAs and the extractable organic fraction of OSPW (OSPW-OF) on mice immune mechanisms. Mice were orally exposed to different C-NA doses, or OSPW-OF at the same NA dose, for up to 8 weeks, and the expression of pro-inflammatory genes in different organs was determined using quantitative PCR. C-NAs and OSPW-OF altered the expression of pro-inflammatory genes, inducing either expression down-regulation or up-regulation, depending on the organ examined and time after exposure. The time at which gene expression alterations occurred, and the specific sets of genes whose expression was altered, were very different between animals exposed to C-NAs or to OSPW-OF. We evaluated the ability of mouse peritoneal macrophages to phagocytose yeast cell wall, as a measure of the ability of mice to mount a central function of the innate immune response. Phagocytosis was significantly reduced in animals exposed to C-NAs, but enhanced in mice exposed to OSPW-OF. Our results indicate that studies using C-NAs may not necessarily reflect the possible effects induced in animals by process water from tailing ponds.

Naphthenic acids speciation and removal during petroleum-coke adsorption and ozonation of oil sands process-affected water.

The Athabasca Oil Sands industry produces large volumes of oil sands process-affected water (OSPW) as a result of bitumen extraction and upgrading processes. Constituents of OSPW include chloride, naphthenic acids (NAs), aromatic hydrocarbons, and trace heavy metals, among other inorganic and organic compounds. To address the environmental issues associated with the recycling and/or safe return of OSPW into the environment, water treatment technologies are required. This study examined, for the first time, the impacts of pretreatment steps, including filtration and petroleum-coke adsorption, on ozonation requirements and performance. The effect of the initial OSPW pH on treatment performance, and the evolution of ozonation and its impact on OSPW toxicity and biodegradability were also examined. The degradation of more than 76% of total acid-extractable organics was achieved using a semi-batch ozonation system at a utilized ozone dose of 150 mg/L. With a utilized ozone dose of 100 mg/L, the treated OSPW became more biodegradable and showed no toxicity towards Vibrio fischeri. Changes in the NA profiles in terms of carbon number and number of rings were observed after ozonation. The filtration of the OSPW did not improve the ozonation performance. Petroleum-coke adsorption was found to be effective in reducing total acid-extractable organics by a 91%, NA content by an 84%, and OSPW toxicity from 4.3 to 1.1 toxicity units. The results of this study indicate that the combination of petroleum-coke adsorption and ozonation is a promising treatment approach to treat OSPW.

Transcriptional and translational regulatory responses to iron limitation in the globally distributed marine bacterium Candidatus pelagibacter ubique.

Iron is recognized as an important micronutrient that limits microbial plankton productivity over vast regions of the oceans. We investigated the gene expression responses of Candidatus Pelagibacter ubique cultures to iron limitation in natural seawater media supplemented with a siderophore to chelate iron. Microarray data indicated transcription of the periplasmic iron binding protein sfuC increased by 16-fold, and iron transporter subunits, iron-sulfur center assembly genes, and the putative ferroxidase rubrerythrin transcripts increased to a lesser extent. Quantitative peptide mass spectrometry revealed that sfuC protein abundance increased 27-fold, despite an average decrease of 59% across the global proteome. Thus, we propose sfuC as a marker gene for indicating iron limitation in marine metatranscriptomic and metaproteomic ecological surveys. The marked proteome reduction was not directly correlated to changes in the transcriptome, implicating post-transcriptional regulatory mechanisms as modulators of protein expression. Two RNA-binding proteins, CspE and CspL, correlated well with iron availability, suggesting that they may contribute to the observed differences between the transcriptome and proteome. We propose a model in which the RNA-binding activity of CspE and CspL selectively enables protein synthesis of the iron acquisition protein SfuC during transient growth-limiting episodes of iron scarcity.

Metformin supplementation and life span in Fischer-344 rats.

Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.

The effect of mannan oligosaccharide supplementation on body weight gain and fat accrual in C57Bl/6J mice.

The prevalence of obesity in industrialized societies has become markedly elevated. In contrast, model organism research shows that reducing caloric intake below ad libitum levels provides many health and longevity benefits. Despite these benefits, few people are willing and able to reduce caloric intake over prolonged periods. Prior research suggests that mannooligosaccharide (MOS or mannan) supplementation can increase lifespan of some livestock and in rodents can reduce visceral fat without reducing caloric intake. Hence, we tested the effect of MOS supplementation as a possible calorie restriction (CR) mimetic (CRM) in mice. C57Bl/6J male mice were fed a high-fat "western" type diet with or without 1% MOS (by weight) supplementation (n = 24/group) from 8 to 20 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake throughout the study. Body weight was measured weekly and body composition (lean and fat mass) measured noninvasively every 3 weeks. Individual fat depot weights were acquired by dissection at study completion. Supplementation of a high-fat diet with 1% MOS tended to reduce total food intake (mean +/- s.d.; control (CON): 293.69 +/- 10.53 g, MOS: 288.10 +/- 11.82 g; P = 0.09) during the study. Moreover, MOS supplementation had no significant effect on final body weight (CON: 25.21 +/- 2.31 g, MOS: 25.28 +/- 1.49 g; P = 0.91), total fat (CON: 4.72 +/- 0.90 g, MOS: 4.82 +/- 0.83 g; P = 0.69), or visceral fat (CON: 1.048 +/- 0.276 g, MOS: 1.004 +/- 0.247 g; P = 0.57). Contrary to previous research, MOS supplementation had no discernable effect on body weight gain or composition during this 12-week study, challenging the potential use of MOS as a CRM or body composition enhancer.

The Bipolar Interactive Psychoeducation (BIPED) study: trial design and protocol.

BACKGROUND: Bipolar disorders affect between 3-5% of the population and are associated with considerable lifelong impairment. Since much of the morbidity associated with bipolar disorder is caused by recurrent depressive symptoms, which are often only poorly responsive to antidepressants, there is a need to develop alternative, non-pharmacological interventions. Psychoeducational interventions have emerged as promising long-term therapeutic options for bipolar disorder. METHODS/DESIGN: The study is an exploratory, individually randomised controlled trial. The intervention known as 'Beating Bipolar' is a psychoeducational programme which is delivered via a novel web-based system. We will recruit 100 patients with a diagnosis of DSM-IV bipolar disorder (including type I and type II) currently in clinical remission. The primary outcome is quality of life. This will be compared for those patients who have participated in the psychoeducational programme with those who received treatment as usual. Quality of life will be assessed immediately following the intervention as well as 10 months after randomisation. Secondary outcomes include current depressive and manic symptoms, number of episodes of depression and mania/hypomania experienced during the follow-up period, global functioning, functional impairment and insight. An assessment of costs and a process evaluation will also be conducted which will explore the feasibility and acceptability of the intervention as well as potential barriers to effectiveness. DISCUSSION: Bipolar disorder is common, under-recognised and often poorly managed. It is a chronic, life-long, relapsing condition which has an enormous impact on the individual and the economy. This trial will be the first to explore the effectiveness of a novel web-based psychoeducational intervention for patients with bipolar disorder which has potential to be easily rolled out to patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81375447.