A shared framework for the common mental disorders and Non-Communicable Disease: key considerations for disease prevention and control.

BACKGROUND: Historically, the focus of Non Communicable Disease (NCD) prevention and control has been cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), cancer and chronic respiratory diseases. Collectively, these account for more deaths than any other NCDs. Despite recent calls to include the common mental disorders (CMDs) of depression and anxiety under the NCD umbrella, prevention and control of these CMDs remain largely separate and independent. DISCUSSION: In order to address this gap, we apply a framework recently proposed by the Centers for Disease Control with three overarching objectives: (1) to obtain better scientific information through surveillance, epidemiology, and prevention research; (2) to disseminate this information to appropriate audiences through communication and education; and (3) to translate this information into action through programs, policies, and systems. We conclude that a shared framework of this type is warranted, but also identify opportunities within each objective to advance this agenda and consider the potential benefits of this approach that may exist beyond the health care system.

Analysis of circadian rhythms from online communities of individuals with affective disorders

The circadian system regulates 24 hour rhythms in biological creatures. It impacts mood regulation. The disruptions of circadian rhythms cause destabilization in individuals with affective disorders, such as depression and bipolar disorders. Previous work has examined the role of the circadian system on effects of light interactions on mood-related systems, the effects of light manipulation on brain, the impact of chronic stress on rhythms. However, such studies have been conducted in small, preselected populations. The deluge of data is now changing the landscape of research practice. The unprecedented growth of social media data allows one to study individual behavior across large and diverse populations. In particular, individuals with affective disorders from online communities have not been examined rigorously. In this paper, we aim to use social media as a sensor to identify circadian patterns for individuals with affective disorders in online communities.We use a large scale study cohort of data collecting from online affective disorder communities. We analyze changes in hourly, daily, weekly and seasonal affect of these clinical groups in contrast with control groups of general communities. By comparing the behaviors between the clinical groups and the control groups, our findings show that individuals with affective disorders show a significant distinction in their circadian rhythms across the online activity. The results shed light on the potential of using social media for identifying diurnal individual variation in affective state, providing key indicators and risk factors for noninvasive wellbeing monitoring and prediction.

A systematic review of adherence to restricted diets in people with functional bowel disorders

Functional bowel disorders such as irritable bowel syndrome are commonly experienced within the population, and have an adverse impact on emotions, physical well-being, social activity, and occupational output. Adherence to a restricted diet can reduce symptoms, which in turn leads to increased quality of life and well-being. The aim of this review was to assess the extent to which predictors of dietary adherence have been considered in studies relating to functional bowel disorders and following a restricted diet. This was done firstly by examining such studies which contained a measure or indicator of adherence, and then by examining predictors of adherence within and between studies. A search of PsycINFO, Medline, CINAHL, Web of Science, and Cochrane databases was performed during July 2014, with the search criteria including relevant terms such as gastrointestinal disorder, irritable bowel syndrome, diet, and adherence. Of an initial 7927 papers, 39 were suitable for inclusion. Fourteen of the 39 studies included had a structured measure or indicator of dietary adherence, and the remaining 25 mentioned adherence without any structured levels of adherence. There was little investigation into the predictors of adherence, with symptom relief or induction being the primary goal of most of the studies. This review indicates that predictors of dietary adherence are rarely considered in research regarding functional bowel disorders. Further investigation is needed into the variables which contribute to rates of adherence to restricted diets, and more rigorous research is needed to characterise those individuals most likely to be non-adherent. Such research is necessary to ensure that people with these conditions can be provided with appropriate support and interventions.

Prospective progression from high-prevalence disorders to bipolar disorder: exploring characteristics of pre-illness stages

BACKGROUND: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated.

METHODS: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests.

RESULTS: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance.

CONCLUSIONS AND LIMITATIONS: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders.

Homocysteine as a potential biomarker in bipolar disorders: a critical review and suggestions for improved studies

Introduction: Homocysteine levels have been associated with major depression, but associations with bipolar disorder remain less clear. Some data suggest homocysteine levels have potential as a biomarker of treatment response; however the literature is mixed.

Areas covered: Oxidized forms of homocysteine can be potentially neurotoxic leading to glutamate toxicity, apoptotic transformation and neurodegenerative processes. High homocysteine may be a risk biomarker for bipolar disorders, but the empirical base remains too weak for firm conclusions. This review discusses the current literature for homocysteine levels as a biomarker.

Expert opinion: It is premature to foreclose the utility of homocysteine levels as a biomarker for bipolar disorder due the methodological inadequacies in the existing literature. These methodological design issues include lack of control for the confounding variables of concurrent medication, phase of bipolar disorder, gender, age, nutritional status, thyroid, liver and renal function, smoking or lean body mass. Well-powered association studies with confounder control could help shed more light on the important clinical question of homocysteine's utility as a biomarker in bipolar disorder. Future experiments are needed to examine the outcome of interventions modulating homocysteine for treating bipolar disorder. Only prospective randomized control trials will provide definitive evidence of the utility of homocysteine as a biomarker or therapeutic target.

Psychiatric disorders, psychotropic medication use and falls among women: an observational study

BACKGROUND: Psychotropic agents known to cause sedation are associated with an increased risk of falls, but the role of psychiatric illness as an independent risk factor for falls is not clear. Thus, this study aimed to investigate the association between psychiatric disorders, psychotropic medication use and falls risk. METHODS: This study examined data collected from 1062 women aged 20-93 yr (median 50 yr) participating in the Geelong Osteoporosis Study, a large, ongoing, population-based study. Depressive and anxiety disorders for the preceding 12-month period were ascertained by clinical interview. Current medication use and falls history were self-reported. Participants were classified as fallers if they had fallen to the ground at least twice during the same 12-month period. Anthropometry, demographic, medical and lifestyle factors were determined. Logistic regression was used to test the associations, after adjusting for potential confounders. RESULTS: Fifty-six women (5.3%) were classified as fallers. Those meeting criteria for depression within the past 12 months had a 2.4-fold increased odds of falling (unadjusted OR = 2.4, 95% CI 1.2-4.5). Adjustment for age and mobility strengthened the relationship (adjusted OR = 2.7, 95% CI 1.4-5.2) between depression and falling, with results remaining unchanged following further adjustment for psychotropic medication use (adjusted OR = 2.7, 95% CI 1.3-5.6). In contrast, past (prior to 12-month) depression were not associated with falls. No association was observed between anxiety and falls risk. Falling was associated with psychotropic medication use (unadjusted OR = 2.8, 95% CI 1.5-5.2), as well as antidepressant (unadjusted OR = 2.4, 95% CI 1.2-4.8) and benzodiazepine use (unadjusted OR = 3.4, 95% CI 1.6-7.3); associations remained unchanged following adjustment for potential confounders. CONCLUSION: The likelihood of falls was increased among those with depression within the past 12 months, independent of psychotropic medication use and other recognised confounders, suggesting an independent effect of depression on falls risk. Psychotropic drug use was also confirmed as an independent risk factor for falls, but anxiety disorders were not. Further research into the underlying mechanisms is warranted.

Factors influencing insulin resistance in relation to atherogenicity in mood disorders, the metabolic syndrome and tobacco use disorder

OBJECTIVE: This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). METHODS: We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. RESULTS: HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. DISCUSSION: The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS.

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

BACKGROUND: Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson's disease, schizophrenia, depression, autism, and chronic fatigue syndrome. DISCUSSION: While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson's disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines. SUMMARY: This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

The population cost-effectiveness of a parenting intervention designed to prevent anxiety disorders in children

BACKGROUND: Prevention and early intervention for anxiety disorders has lagged behind many other forms of mental disorder. Recent research has demonstrated the efficacy of a parent-focussed psycho-educational programme. The programme is directed at parents of inhibited preschool children and has been shown to reduce anxiety disorders at 1 and 3 years following intervention. The current study assesses the cost-effectiveness of this intervention to determine whether it could provide value-for-money across a population. METHOD: A cost-utility economic framework, using Disability-Adjusted-Life-Years (DALYs) as the outcome, was adopted. Economic modelling techniques were used to assess the incremental cost-effectiveness ratio (ICER) of the intervention within the Australian population context, which was modelled as add-on to current practice. The perspective was the health sector. Uncertainty was measured using multivariate probabilistic testing and key assumptions were tested using univariate sensitivity analysis. RESULTS: The median ICER for the intervention was AUD$8,000 per DALY averted with 99.8% of the uncertainty iterations falling below the threshold value-for-money criterion of AUD$50,000 per DALY averted. The results were robust to sensitivity testing. CONCLUSIONS: Screening young children in a preschool setting for an inhibited temperament and providing a brief intervention to the parents of children with high levels of inhibition appears to provide very good value-for-money and worth considering in any package of preventive care. Further evaluation of this intervention under routine health service conditions will strengthen conclusions. Acceptability issues associated with this intervention, particularly to preschool staff and parents, need to be considered before wide-scale adoption is undertaken.

Composition of fuel stores and digestive limitations to fuel deposition rate in the long-distance migratory thrush nightingale, Luscinia luscinia

During their autumn migratory phase, thrush nightingales (Luscinia luscinia) previously starved for 2 d were allowed to refuel under three different ambient temperature conditions (-7 degrees, 7 degrees, and 22 degrees C). During the refueling period, as well as during the preceding control and starvation periods, food intake, body mass, and feces production were monitored. In addition, daily energy expenditure was measured during the refueling period. The compilation of the energy balance during the refueling period revealed an energy density of the deposited tissue of 33.6 kJ g-1. Assuming that the deposited tissue consists of fat and protein exclusively, with energy densities of 39.6 and 5.5 kJ g-1 wet mass, respectively, we estimated the deposited tissue to consist of 82% fat and 18% wet protein (6% dry protein and 12% water). Nitrogen balances during control, starvation, and refueling phases and during a period of prolonged and complete starvation indicated that 5% of the nutrient stores consisted of dry protein. Our results support recent findings that nutrient stores for migration often contain protein in addition to fat and consequently are 15%-25% less energy rich than pure fat stores. These proteins might be stored as muscle or other functional tissue and may be required to support the extra mass of the stores and/or reflect an incapacity of the metabolic machinery to catabolize far exclusively. Fuel deposition rate was positively related with ambient temperature, whereas food intake rate was unaffected by temperature. These results indicate that the rate of fuel deposition is limited by a ceiling in food intake rate; when this ceiling is reached, fuel deposition rate is negatively affected by daily energy expenditure rate. To a certain extent, the ceiling in food intake rate varies depending on feeding conditions over the previous days. These variations in food intake capacity probably reflect the building and breakdown of gut tissues and/or gut enzyme systems and might be insensible and not evolutionary adaptive. Significant energetic costs, however, are probably associated with the maintenance of gut tissues. It is therefore feasible that changes in digestive capacity are regulated and are directed at energy economization.

Zebrafish as a model for leukemia and other hematopoietic disorders

Zebrafish is an established model for the study of vertebrate development, and is especially amenable for investigating hematopoiesis, where there is strong conservation of key lineages, genes, and developmental processes with humans. Over recent years, zebrafish has been increasingly utilized as a model for a range of human hematopoietic diseases, including malignancies. This review provides an overview of zebrafish hematopoiesis and describes its application as a model of leukemia and other hematopoietic disorders.

A new social-family model for eating disorders: A European multicentre project using a case-control design

OBJECTIVE: To examine a new socio-family risk model of Eating Disorders (EDs) using path-analyses. METHOD: The sample comprised 1264 (ED patients = 653; Healthy Controls = 611) participants, recruited into a multicentre European project. Socio-family factors assessed included: perceived maternal and parental parenting styles, family, peer and media influences, and body dissatisfaction. Two types of path-analyses were run to assess the socio-family model: 1.) a multinomial logistic path-model including ED sub-types [Anorexia Nervosa-Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as the key polychotomous categorical outcome and 2.) a path-model assessing whether the socio-family model differed across ED sub-types and healthy controls using body dissatisfaction as the outcome variable. RESULTS: The first path-analyses suggested that family and media (but not peers) were directly and indirectly associated (through body dissatisfaction) with all ED sub-types. There was a weak effect of perceived parenting directly on ED sub-types and indirectly through family influences and body dissatisfaction. For the second path-analyses, the socio-family model varied substantially across ED sub-types. Family and media influences were related to body dissatisfaction in the EDNOS and control sample, whereas perceived abusive parenting was related to AN-BP and BN. DISCUSSION: This is the first study providing support for this new socio-family model, which differed across ED sub-types. This suggests that prevention and early intervention might need to be tailored to diagnosis-specific ED profiles.

Sarcopenia and the common mental disorders: a potential regulatory role of skeletal muscle on brain function?

While it is understood that body composition impacts on physical conditions, such as diabetes and cardiovascular disease, it is only now apparent that body composition might play a role in the genesis of common mental disorders, depression and anxiety. Sarcopenia occurs in ageing and comprises a progressive decline in muscle mass, strength and function, leading to frailty, decreased independence and poorer quality of life. This review presents an emerging body of evidence to support the hypothesis that shared pathophysiological pathways for sarcopenia and the common mental disorders constitute links between skeletal muscle and brain function. Contracting skeletal muscle secretes neurotrophic factors that are known to play a role in mood and anxiety, and have the dual role of nourishing neuronal growth and differentiation, while protecting the size and number of motor units in skeletal muscle. Furthermore, skeletal muscle activity has important immune and redox effects that impact behaviour and reduce muscle catabolism.

The deleterious effects of oxidative and nitrosative stress on palmitoylation, membrane lipid rafts and lipid-based cellular signalling : new drug targets in neuroimmune disorders

Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

Cigarette smoking and increased anxiety symptoms and disorders

 This research project demonstrated that exposure to cigarette smoke in adolescence, childhood and in utero is prospectively associated with increased levels of anxiety later in life. The results suggest smoking is a plausible risk factor for developing higher levels of anxiety, informing multiple areas for future research into anxiety pathogenesis.