Large-scale Roll Out of Electronic Longitudinal Mood-Monitoring for Research in Affective Disorders: Report From the UK Bipolar Disorder Research Network

Background Electronic longitudinal mood monitoring has been shown to be acceptable to patients with affective disorders within clinical settings, but its use in large-scale research has not yet been established. Methods Using both postal and email invitations, we invited 4080 past research participants with affective disorders who were recruited into the Bipolar Disorder Research Network (BDRN) over a 10 year period to participate in online weekly mood monitoring. In addition, since January 2015 we have invited all newly recruited BDRN research participants to participate in mood monitoring at the point they were recruited into BDRN. Results Online mood monitoring uptake among past participants was 20, and among new participants to date was 46 with participants recruited over the last year most likely to register (61). More than 90 mood monitoring participants engaged for at least one month, with mean engagement period greater than one year (58 weeks) and maximum engagement for longer than three years (165 weeks). There were no significant differences in the proportion of past and new BDRN participants providing data for at least 4 weeks (91, 92 respectively), 3 months (78, 82), 6 months (65, 54) or one year (51, 44). Limitations Our experiences with recruiting participants for electronic prospective mood monitoring may not necessarily generalise fully to research situations that are very different from those we describe. Conclusions Large-scale electronic longitudinal mood monitoring in affective disorders for research purposes is feasible with uptake highest among newly recruited participants

Consistency of the Disposition Index in the Face of Diet Induced Insulin Resistance: Potential Role of FFA

Objective Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. Methods In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance. Results Hypercaloric high fat feeding in dogs resulted in modest weight gain, and an increase in adipose tissue with no change in the non-adipose tissue size. To compensate for the drop in insulin sensitivity, there was a significant rise in plasma insulin, which can be attributed in part to a decrease in the metabolic clearance rate of insulin and increased insulin secretion. In this study we observed complete compensation for high fat diet induced insulin resistance as measured by the disposition index. The compensatory hyperinsulinemia was coupled with significant changes in plasma FFAs and no change in plasma glucose. Conclusions We postulate that early in the development of diet induced insulin resistance, a change in plasma FFAs may directly, through signaling at the level of β-cell, or indirectly, by decreasing hepatic insulin clearance, result in the observed hyperinsulinemic compensation

Right care, right time, right place: improving outcomes for people with spinal cord injury through early access to intervention and improved access to specialised care: study protocol

Background: Traumatic spinal cord injury is a devastating condition impacting adversely on the health and wellbeing, functioning and independence, social participation and quality of life of the injured person. In Australia, there are approximately 15 new cases per million population per year; economic burden estimates suggest 2 billion dollars annually. For optimal patient outcomes expert consensus recommends expeditious transfer (“24 hours) in a Spinal Cord Injury Unit. Examining current health service and clinical intervention pathways in this Australian population-based sample, in relation to their outcomes, will provide an understanding of factors associated with patient flow, resource utilisation and cost, and patient and family quality of life. Barriers to streamlined effective early-care pathways and facilitators of optimal treatment for these patients will be identified

History of Premenstrual Mood Change and Postpartum Episodes are Associated with Perimenopausal Episodes in Women with Bipolar Disorder

Background and Aims: Reproductive life events are potential triggers of mood episodes in women with bipolar disorder. We aimed to establish whether a history of premenstrual mood change and postpartum episodes are associated with perimenopausal episodes in women who have bipolar disorder. Methods: Participants were 339 post-menopausal women with DSM-IV bipolar disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Women self-reported presence (N = 200) or absence (N = 139) of an illness episode during the perimenopausal period. History of premenstrual mood change was measured using the self-report Premenstrual Symptoms Screening Tool (PSST), and history of postpartum episodes was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry, SCAN) and inspection of case-notes. Results: History of a postpartum episode within 6 months of delivery (OR = 2.13, p = 0.03) and history of moderate/severe premenstrual syndrome (OR = 6.33, p < 0.001) were significant predictors of the presence of a perimenopausal episode, even after controlling for demographic factors. When we narrowed the definition of premenstrual mood change to premenstrual dysphoric disorder, it remained significant (OR = 2.68, p = 0.007). Conclusions: Some women who have bipolar disorder may be particularly sensitive to reproductive life events. Previous mood episodes in relation to the female reproductive lifecycle may help clinicians predict individual risk for women with bipolar disorder approaching the menopause. There is a need for prospective longitudinal studies of women with bipolar disorder providing frequent contemporaneous ratings of their mood to overcome the limitations of retrospective self-report data

Psychotropic medications in older people in residential care facilities and associations with quality of life: a cross-sectional study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Psychotropic medications have been associated with many adverse outcomes in older people living in residential care. Home-like models of residential care may be preferable to traditional models of care and we hypothesized that this model may impact on the prevalence of psychotropic medications. The objectives were to: 1) examine associations between psychotropic medications and quality of life in older adults living in residential care facilities with a high prevalence of cognitive impairment and dementia and 2) determine if there was a difference in prevalence of psychotropic medications in facilities which provide a small group home-like model of residential care compared to a ‘standard model’ of care. Methods Participants included 541 residents from 17 residential aged care facilities in the Investigating Services Provided in the Residential Environment for Dementia (INSPIRED) study. Cross-sectional analyses were completed to examine the above objectives. Quality of life was measured with the dementia quality of life questionnaire (DEMQOL) and the EQ-5D-5L completed by the resident or a proxy. Results Overall, 70.8% (n = 380) of the population had been prescribed/dispensed at least one psychotropic medication in the 100 days prior to recruitment. An increased number of psychotropic medications was associated with lower quality of life according to DEMQOL-Proxy-Utility scores (β (SE): − 0.012 (0.006), p = 0.04) and EQ-5D-5L scores (− 0.024 (0.011), p = 0.03) after adjustment for resident-level and facility-level characteristics. Analysis of the individual classes of psychotropic medications showed antipsychotics were associated with lower DEMQOL-Proxy-Utility scores (− 0.030 (0.014), p = 0.03) and benzodiazepines were associated with lower EQ-5D-5L scores (− 0.059 (0.024), p = 0.01). Participants residing in facilities which had a home-like model of residential care were less likely to be prescribed psychotropic medications (OR (95% CI): 0.24 (0.12, 0.46), p < 0.001). Conclusions An increased number of psychotropic medications were associated with lower quality of life scores. These medications have many associated adverse effects and the use of these medications should be re-examined when investigating approaches to improve quality of life for older people in residential care. Home-like models of residential care may help to reduce the need for psychotropic medications, but further research is needed to validate these findings

Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.

BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression

The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: Associations and evidence for gene-environment correlation and gene-environment interaction

ObjectiveS: Research implicates the A1 allele of the dopamine D2 receptor gene (DRD2) Taq1A polymorphism in the development of depression and anxiety. Furthermore, recent papers suggest that children with A1 allele of this gene may receive less positive parenting, and that the effects of this gene on child symptoms may be moderated by parenting. We sought to replicate and extend these findings using behavioral measures in a nonclinical sample of young children. Methods: In a sample of 473 preschool-aged children and their mothers, structured clinical interview measures and maternal reports of child symptoms were collected, and standardized observations of parent-child interactions were conducted. Results: An association was detected between the DRD2 A1 allele and symptoms of depression and anxiety indexed using interview and parent report methods. As found in previous reports, children with the DRD2 A1 allele received less supportive parenting and displayed higher levels of negative emotionality during parent-child interactions. Tests of mediation and moderation were conducted. Conclusion: We found associations between the DRD2 A1 allele and early-emerging anxious and depressive symptoms in a community sample of preschool-aged children, and evidence of a gene-environment correlation and moderation of the main effect of child genotype on child symptoms by parenting. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation

Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 μM, whereas TNC-3 was only detectable at 100 μM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 μM. CD4+T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4+T-cells was prevented by prior incubation with dynole 34-2 (50 μM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4+T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases