Funding for mental health research: the gap remains

Objectives: To examine the levels and growth rates of absolute funding to mental health research from 2001 to 2010, compared with other National Health Priority Areas (NHPAs), and the relative rate of mental health funding compared with other NHPAs, by taking disease burden into account. The quality of Australian research in mental health was also examined using objective indicators of research strength. Design and setting: Retrospective analysis of levels of funding overall and as a function of mental health domains using data from the National Health and Medical Research Council, with and without adjustment for burden of disease. A keyword analysis was used to assess the success rate of mental health project grant applications. Objective indicators of the quality of Australian mental health research were sought from citation indicators. Main outcome measures: Funding for mental health research relative to disease burden; funding according to disease category; project grant success rates. Results: Using actual and adjusted figures, mental health research received a lower proportion of health funding than other NHPAs, including cancer, diabetes and cardiovascular disease. Research projects into substance misuse and autism were proportionately better funded than those in anxiety, depression or schizophrenia. A significant proportion of mental health research funding was awarded to research into ageing. Citation data indicated that mental health research in Australia performed better than research in neuroscience, clinical medicine, microbiology, and pharmacology and toxicology, and at a comparable level to immunology research, despite poor levels of funding. Conclusions: Low levels of funding for mental health research appear to be largely attributable to low capacity. Mental health research in Australia is of high quality, and efforts are needed to build capacity

Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia

Objectives: Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Methods: Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised. Results: Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP amplitudes than controls. LPP amplitude correlated with task performance however amplitudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 amplitude or latency were observed. Conclusions: The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia

Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

BACKGROUND: Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia. METHODS: Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. RESULTS: We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. LIMITATIONS: Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables. CONCLUSION: Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life

Problem gambling and substance use in patients attending community mental health services

Relatively little is known about co-occurring gambling problems and their overlap with other addictive behaviors among individuals attending mental health services. We aimed to determine rates of gambling and substance use problems in patients accessing mental health services in Victoria, Australia. Methods A total of 837 adult patients were surveyed about their gambling and administered standardized screening tools for problem gambling and harmful tobacco, alcohol, and drug use. Prevalence of gambling problems was estimated and regression models used to determine predictors of problem gambling. Results The gambling participation rate was 41.6% [95% CI = 38.2–44.9]. The Problem Gambling Severity Index identified 19.7% [CI = 17.0–22.4] as “non-problem gamblers,” 7.2% [CI = 5.4–8.9] as “low-risk” gamblers, 8.4% [CI = 6.5–10.2] as “moderate-risk” gamblers, and 6.3% [CI = 4.7–8.0] as “problem gamblers.” One-fifth (21.9%) of the sample and 52.6% of all gamblers were identified as either low-risk, moderate-risk, or problem gamblers (PGs). Patients classified as problem and moderate-risk gamblers had significantly elevated rates of nicotine and illicit drug dependence (p  Discussion and conclusions Patients were less likely to gamble, but eight times as likely to be classified as PG, relative to Victoria’s adult general population. Elevated rates of harmful substance use among moderate-risk and PG suggest overlapping vulnerability to addictive behaviors. These findings suggest mental health services should embed routine screening into clinical practice, and train clinicians in the management of problem gambling

Impact of cannabis use on long-term remission in bipolar I and schizoaffective disorder

OBJECTIVE: To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders

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 &lsquo;real-world&rsquo; 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&thinsp;=&thinsp;155) alone, or olanzapine with, or without, CMS (olanzapine&thinsp;&plusmn;&thinsp;CMS; n&thinsp;=&thinsp;84) were assessed every 3&thinsp;months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale &ndash; 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&thinsp;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&thinsp;&plusmn;&thinsp;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.<br /

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study Funding/Competing Interest(S) The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Estrogens and gonadal function in schizophrenia and related psychoses

Recent research has increasingly pointed to the importance of estrogens and the hypothalamic-pituitary-gonadal axis in schizophrenia. Specifically, there is mounting evidence from clinical, epidemiological, and basic research that estradiol, the main component of estrogens, exerts protective effects in schizophrenia and related psychoses. Possible modes of action of this hormone in the brain have been suggested, and clinical intervention studies have reported the first positive results. Furthermore, there are an increasing number of reports on gonadal dysfunction and states of estrogen deficiency in women with schizophrenia. These findings could have important implications for clinicians and researchers alike