Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1.

Intercellular propagation of aggregated protein inclusions along actin-based tunneling nanotubes (TNTs) has been reported as a means of pathogenic spread in Alzheimer's, Parkinson's, and Huntington's diseases. Propagation of oligomeric-structured polyglutamine-expanded ataxin-1 (Atxn1[154Q]) has been reported in the cerebellum of a Spinocerebellar ataxia type 1 (SCA1) knock-in mouse to correlate with disease propagation. In this study, we investigated whether a physiologically relevant polyglutamine-expanded ATXN1 protein (ATXN1[82Q]) could propagate intercellularly. Using a cerebellar-derived live cell model, we observed ATXN1 aggregates form in the nucleus, subsequently form in the cytoplasm, and finally, propagate to neighboring cells along actin-based intercellular connections. Additionally, we observed the facilitation of aggregate-resistant proteins into aggregates given the presence of aggregation-prone proteins within cells. Taken together, our results support a pathogenic role of intercellular propagation of polyglutamine-expanded ATXN1 inclusions.

Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale.

BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

MoodNetwork: An Innovative Approach to Patient-centered Research.

INTRODUCTION: Research has often been viewed as a passive process by which participants enroll in studies developed by researchers. It is becoming clearer that to understand the nuances of mood episodes and how to prevent them, we need to conduct large clinical trials that have the power to investigate moderators and mediators, or catalysts and mechanisms of change. MoodNetwork, the first online, patient-centered research community for individuals with mood disorders, aims to change the way that traditional research has been conducted by involving patients, their caregivers, and advocates in the process of research. The aim of this report is to share lessons learned from developing MoodNetwork. METHODS: Participants enroll by completing a demographic survey and consent form. Once enrolled, participants are encouraged to complete optional surveys about their mood disorders and areas of research priority. Stakeholder and advocacy partners developed the website, web-based surveys, and recruitment materials. RESULTS: MoodNetwork has enrolled 4103 participants to date. Of this sample, 96.9% report experiencing depression and 79.7% endorse symptoms of mania or hypomania. Participants rated reducing stigma and alleviating symptoms as their 2 largest research priorities. Recruitment has been slower than expected. Recruiting a diverse sample has been challenging, and this impacts the Network's ability to conduct comparative effectiveness research studies. DISCUSSION: We discuss lessons learned from recruiting individuals with mood disorders to MoodNetwork, an innovative approach to conducting clinical trials. We identify and review 5 strategies for increasing enrollment as well as future directions.

Examining the Feasibility and Acceptability of an Online Yoga Class for Mood Disorders: A MoodNetwork Study.

BACKGROUND: Despite ongoing advances in the treatment of mood disorders, a substantial proportion of people diagnosed with major depression or bipolar disorder remain symptomatic over time. Yoga, which has been shown to reduce stress and depressive symptoms, as well as to improve overall quality of life, shows promise as an adjunctive treatment. However, dissemination of yoga for clinical populations remains challenging. The purpose of this pilot study was to test the feasibility and acceptability of an online yoga intervention for individuals with mood disorders. METHODS: In total, 56 adults who reported being diagnosed with a mood disorder (bipolar disorder, major depressive disorder, cyclothymia, or schizoaffective disorder) were recruited from MoodNetwork, an online community of individuals with mood disorders. A feedback survey and a measure of positive and negative affect were administered before and after a 30-minute online Hatha yoga class. RESULTS: In total, 44 individuals (78.6%) completed all components of the yoga class. The mean score on a 10-point Likert scale rating how much participants liked the online yoga class was 7.24 (SD=2.40). Most participants (67.9%) reported that they would be "somewhat likely" or "very likely" to participate in an online yoga program again. There was a statistically significant decrease in negative affect after completing the class (t=-6.05; P<0.001), but positive affect did not change (P>0.10). DISCUSSION: These preliminary data support the utility of online yoga tailored specifically for people with mood disorders as a possible adjunctive intervention that warrants further investigation.

Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial.

BACKGROUND: Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders. METHODS: Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response. RESULTS: Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms. LIMITATIONS: This was a pilot feasibility and acceptability trial; results should be interpreted with caution. CONCLUSIONS: Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety.

Getting to wellness: The potential of the athletic model of marginal gains for the treatment of bipolar disorder.

OBJECTIVE: People with bipolar disorder frequently have persistent symptoms, continued problems functioning and comorbid medical conditions. We propose applying the athletic coaching concept of marginal gains to help patients address these challenges to achieve wellness. METHOD: We review the concept of marginal gains and potential interventions to improve long-term outcomes for bipolar patients. RESULTS: Evidence exists to help bipolar patients with diet and exercise, gradual behavioral change, mobile applications and peer support. CONCLUSION: Marginal gains, small and doable improvements across a broad range of areas, have great potential to improve the lives of people with bipolar disorder.

Improving the care of patients who have treatment-resistant depression: the promise of the PCORnet Mood Network.

In this issue of JCP, Zhou and colleagues review and integrate placebo-controlled efficacy trials of medications for treatment-resistant depression (TRD) to compare efficacy in a meta-analysis. They conclude that, among 11 augmentation options for TRD, aripiprazole and quetiapine have the most robust evidence for efficacy, with the caveats that these treatments carry substantial risks of adverse events and no long-term data are available. In the absence of direct comparisons, this exercise highlights the formidable challenges that clinicians face when making decisions.

A Reliable and Valid Survey to Predict a Patient's Gagging Intensity.

OBJECTIVES: The aim of this study was to devise a reliable and valid survey to predict the intensity of someone's gag reflex. MATERIAL AND METHODS: A 10-question Predictive Gagging Survey was created, refined, and tested on 59 undergraduate participants. The questions focused on risk factors and experiences that would indicate the presence and strength of someone's gag reflex. Reliability was assessed by administering the survey to a group of 17 participants twice, with 3 weeks separating the two administrations. Finally, the survey was given to 25 dental patients. In these cases, patients completed an informed consent form, filled out the survey, and then had a maxillary impression taken while their gagging response was quantified from 1 to 5 on the Fiske and Dickinson Gagging Intensity Index. RESULTS: There was a moderate positive correlation between the Predictive Gagging Survey and Fiske and Dickinson's Gagging Severity Index, r = +0.64, demonstrating the survey's validity. Furthermore, the test-retest reliability was r = +0.96, demonstrating the survey's reliability. CONCLUSIONS: The Predictive Gagging Survey is a 10-question survey about gag-related experiences and behaviours. We established that it is a reliable and valid method to assess the strength of someone's gag reflex.