Perturbed iron biology in the prefrontal cortex of people with schizophrenia.

Despite loss of grey matter volume and emergence of distinct cognitive deficits in young adults diagnosed with schizophrenia, current treatments for schizophrenia do not target disruptions in late maturational reshaping of the prefrontal cortex. Iron, the most abundant transition metal in the brain, is essential to brain development and function, but in excess, it can impair major neurotransmission systems and lead to lipid peroxidation, neuroinflammation and accelerated aging. However, analysis of cortical iron biology in schizophrenia has not been reported in modern literature. Using a combination of inductively coupled plasma-mass spectrometry and western blots, we quantified iron and its major-storage protein, ferritin, in post-mortem prefrontal cortex specimens obtained from three independent, well-characterised brain tissue resources. Compared to matched controls (n = 85), among schizophrenia cases (n = 86) we found elevated tissue iron, unlikely to be confounded by demographic and lifestyle variables, by duration, dose and type of antipsychotic medications used or by copper and zinc levels. We further observed a loss of physiologic age-dependent iron accumulation among people with schizophrenia, in that the iron level among cases was already high in young adulthood. Ferritin, which stores iron in a redox-inactive form, was paradoxically decreased in individuals with the disorder. Such iron-ferritin uncoupling could alter free, chemically reactive, tissue iron in key reasoning and planning areas of the young-adult schizophrenia cortex. Using a prediction model based on iron and ferritin, our data provide a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicate that achievement of optimal cortical iron homeostasis could offer a new therapeutic target.

CogTale: an online platform for the evaluation, synthesis, and dissemination of evidence from cognitive interventions studies.

Systematic reviews and meta-analyses are critical in health-related decision-making, and are considered the gold standard in research synthesis methods. However, with new trials being regularly published and with the development of increasingly rigorous standards of data synthesis, systematic reviews often require much expertise and long periods of time to be completed. Automation of some of the steps of evidence synthesis productions is a promising improvement in the field, capable of reducing the time and costs associated with the process.This article describes the development and main characteristics of a novel online repository of cognitive intervention studies entitled Cognitive Treatments Article Library and Evaluation (CogTale). The platform is currently in a Beta Release phase, as it is still under development. However, it already contains over 70 studies, and the CogTale team is continuously coding and uploading new studies into the repository. Key features include advanced search options, the capability to generate meta-analyses, and an up-to-date display of relevant published studies.

What is OSFED? The predicament of classifying 'other' eating disorders.

The transition from DSM-IV to DSM-5 relaxed diagnostic criteria for anorexia nervosa and bulimia nervosa, and recognised a third eating disorder, binge eating disorder. However, a large proportion of cases remain in the ill-defined category of 'other specified feeding and eating disorders'. We sought to investigate the utility of a proposed solution to classify this group further, subdividing based on the dominant clinical feature: binge eating/purging or restraint. Cluster analysis failed to identify clusters in a treatment-seeking sample based on symptoms of restraint, binge eating, purging and over-evaluation of shape and weight. Further investigation of this highly heterogeneous group is required.

Australian Smokers' Sensory Experiences and Beliefs Associated with Menthol and Non-Menthol Cigarettes.

Many current smokers incorrectly believe that menthol cigarettes are less harmful, likely due to the biological and sensory effects of menthol, which can lead smokers to have favourable sensory experiences. In this study, we measured the extent to which Australian smokers associate certain sensory experiences with smoking menthol and non-menthol cigarettes, and their beliefs about how damaging and enjoyable they find cigarettes with each of these sensory experiences. A sample of 999 Australian 18-69-year-old weekly smokers was recruited from a non-probability online panel; this study focuses on the 245 respondents who currently smoked menthol cigarettes at least once per week. Current menthol smokers were four to nine times more likely to experience menthol rather than non-menthol cigarettes as having favourable sensory experiences, including feeling smooth, being soothing on the throat, fresh-tasting and clean-feeling. Menthol smokers perceived cigarettes with these favourable sensations as less damaging and more enjoyable than cigarettes with the opposite more aversive sensory experience. Efforts to correct these misperceptions about risk will likely require messages that provide new information to help smokers understand that these sensations do not indicate a lower level of risk. Banning menthol in tobacco products-as has recently been done in some nations-would also be a timely and justified strategy for protecting consumers.

The schizophrenia genetics knowledgebase: a comprehensive update of findings from candidate gene studies.

Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.

Blood and brain protein levels of ubiquitin-conjugating enzyme E2K (UBE2K) are elevated in individuals with schizophrenia.

A number of recent studies have suggested the ubiquitin proteasome system (UPS) in schizophrenia is dysfunctional. The purpose of this study was to investigate UBE2K, a ubiquitin-conjugating (E2) enzyme within the UPS that has been associated with psychosis symptom severity, in the blood and brain of individuals with schizophrenia. Whole blood and erythrocytes from 128 (71 treatment-resistant schizophrenia, 57 healthy controls) individuals as well as frozen dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) post-mortem samples from 74 (37 schizophrenia, 37 controls) individuals were obtained. UBE2K gene expression was assayed in whole blood and DLPFC samples, whereas protein levels were assayed in erythrocytes and OFC samples. Elevated levels of UBE2K mRNA were observed in whole blood of individuals with schizophrenia (p = 0.03) but not in the DLPFC, while protein levels were raised in erythrocytes and the OFC (p < 0.001 and p = 0.002 respectively). Findings were not better explained by age, smoking, clozapine plasma levels or duration of illness. Although blood and brain samples were derived from independent samples, our findings suggest peripheral protein levels of UBE2K may serve as a surrogate of brain levels and further supports the notion of UPS dysfunction in schizophrenia. Future studies to determine the pathophysiological effects of elevated UBE2K protein levels in the brain of those with schizophrenia are warranted.

Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia.

Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem OFC tissue from 76 (38 schizophrenia, 38 control) matched individuals, as well as erythrocytes from 181 living participants, who comprised 30 individuals with recent onset schizophrenia (mean illness duration = 1 year), 63 individuals with 'treatment-resistant' schizophrenia (mean illness duration = 17 years), and 88 age-matched participants without major psychiatric illness. Ubiquitinated protein levels were elevated in postmortem OFC in schizophrenia compared to controls (p = <0.001, AUC = 74.2%). Similarly, individuals with 'treatment-resistant' schizophrenia had higher levels of ubiquitinated proteins in erythrocytes compared to those with recent onset schizophrenia (p < 0.001, AUC = 65.5%) and controls (p < 0.001, AUC = 69.4%). The results could not be better explained by changes in proteasome activity, demographic, medication, or tissue factors. Our results suggest that ubiquitinated protein formation may be abnormal in both the brain and erythrocytes of those with schizophrenia, particularly in the later stages or specific sub-groups of the illness. A derangement in protein ubiquitination may be linked to pathogenesis or neurotoxicity in schizophrenia, and its manifestation in the blood may have prognostic utility.

Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials.

AIM: To conducted a systematic review and meta-analysis of prospective, randomized controlled trials (RCTs) that examined pharmacogenetic-guided decision support tools (DSTs) relevant to depressive symptom remission in major depressive disorder (MDD). PATIENTS & METHODS: Random-effects meta-analysis was performed on RCTs that examined the effect of DSTs on remission rates in MDD. RCT quality was assessed using the Cochrane Collaboration Criteria. RESULTS & CONCLUSION: A total of 1737 eligible subjects from five RCTs were examined. Individuals receiving pharmacogenetic-guided DST therapy (n = 887) were 1.71 (95% CI: 1.17-2.48; p = 0.005) times more likely to achieve symptom remission relative to individuals who received treatment as usual (n = 850). Pharmacogenetic-guided DSTs might improve symptom remission among those with MDD.

The capacity of the BATCH as a predictive tool for discharge planning for people with neuropsychiatric disorders.

BACKGROUND/AIM: Assessment of cognitive function in people with neurosychiatric disorders can be challenging, due to behavioural and psychiatric symptomatology. The Behavioural Assesment Tool for Cognition and Higher Functioning (BATCH) is a validated observational tool that complements formal cognitive testing in this patient population. This study aimed to determine the capacity of the BATCH as a predictive tool for discharge planning. METHOD: BATCH scores for 330 consecutive admissions for assessment to a specialist neuropsychiatry unit between 2007 and 2015 were analysed. The variables of interest included discharge destination, diagnosis, length of stay, age at discharge and BATCH scores (both subdomain and total). Significant predictors of discharge destination were identified using logistic regression analysis. RESULTS: After adjusting for age at discharge, three variables were found to be significant predictors of discharge destination - length of stay, diagnosis, and BATCH total score. The odds of being discharged to a destination other than home decreased by 3% for each additional BATCH total score unit. The length of stay remained a significant predictor of discharge destination when adjusting for BATCH total score, age at admission and diagnosis. CONCLUSION: BATCH total scores, but not subdomain scores, were predictive of discharge destination, along with the patients' length of stay and diagnosis. Knowledge of this relationship may guide clinical discharge planning, when working with the complex needs of this group of patients. A larger study is indicated to determine the range and cut-off scores for discharge destinations other than home.

Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders.

Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.

Development and validation of a mental health screening tool for asylum-seekers and refugees: the STAR-MH.

BACKGROUND: There is no screening tool for major depressive disorder (MDD) or post-traumatic stress disorder (PTSD) in asylum-seekers or refugees (ASR) that can be readily administered by non-mental health workers. Hence, we aimed to develop a brief, sensitive and rapidly administrable tool for non-mental health workers to screen for MDD and PTSD in ASR. METHODS: The screening tool was developed from an extant dataset (n = 121) of multiply screened ASR and tested prospectively (N = 192) against the M.I.N.I. (Mini International Neuropsychiatric Interview) structured psychiatric interview. Rasch, Differential Item Functioning and ROC analyses evaluated the psychometric properties and tool utility. RESULTS: A 9-item tool with a median administration time of six minutes was generated, comprising two 'immediate screen-in' items, and a 7-item scale. The prevalence of PTSD &/or MDD using the M.I.N.I. was 32%, whilst 99% of other diagnosed mental disorders were comorbid with one or both of these. Using a cut-score of ≥2, the tool provided a sensitivity of 0.93, specificity of 0.75 and predictive accuracy of 80.7%. CONCLUSIONS: A brief sensitive screening tool with robust psychometric properties that was easy to administer at the agency of first presentation was developed to facilitate mental health referrals for asylum-seekers and new refugees.

Morphine use in cancer care: A survey of attitudes and perceptions in general practice patients.

BACKGROUND: Morphine is widely prescribed for patients with cancer, although a number of attitudes have been cited as barriers to its use, including fear, addiction and associations with death. The aim of this study was to explore the nature of these beliefs, and assess the extent to which these attitudes exist in a general practice patient population that may require morphine in the future. METHODS: A 30-item survey was distributed through general practices in Victoria, Australia. RESULTS: Of the 379 questionnaires distributed, 290 were collected (76.5%). Participants were predominantly neutral on questions regarding the effect of morphine on the duration of life. Morphine was seen to be prescribed responsibly (73.5%), even while most perceived its potential for addiction (69.7%). Participants with experience of morphine use had more negative perceptions regarding its efficacy. DISCUSSION: Conversations regarding morphine use should include a discussion about the beliefs and experiences of the individual, many of which may reinforce the utility of morphine.

The Mental Health in Diabetes Service (MINDS) to enhance psychosocial health: study protocol for a randomized controlled trial.

BACKGROUND: After a diagnosis of diabetes mellitus, people not only have to cope with the physical aspects and common complications that require daily self-management, they are also faced with ongoing psychosocial challenges. Subsequently they find themselves having to navigate the health system to engage multidisciplinary supports; the combination of these factors often resulting in reduced health-related quality of life. To maintain optimal diabetes control, interventions need to incorporate psychosocial supports and a skill base for disease management. Therefore, our aim was to evaluate an 'Optimal Health Program' that adopts a person-centred approach and engages collaborative therapy to educate and support the psychosocial health of people diagnosed with type I or II diabetes. METHODS: This prospective randomised controlled trial will include 166 people diagnosed with diabetes: 83 in the intervention (Optimal Health Program) and 83 in the control (usual care) group. Participants with type diabetes mellitus will be recruited through hospital outpatient clinics and diabetes community organisations. Participants in the intervention group will receive nine (8 + 1 booster session) sequential sessions, based on a structured treatment manual emphasising educational and psychosocial support self-efficacy and skills building. The primary outcome measures will be generalised self-efficacy (GSE) and health-related quality of life (AQoL-6D and EQ-5D). Secondary measures will be anxiety and depression (HADS), social and workplace functioning (WSAS), diabetes-related quality of life (DQoL), diabetes-related distress (PAID), and type of coping strategies (Brief COPE). In addition, a health economic cost analysis and process evaluations will be performed to assess the economic cost and efficacy of the program's operations, implementation and service delivery. DISCUSSION: We envisage that the Optimal Health Program's emphasis on self-efficacy and self-management will provide participants with the skills and knowledge to achieve increased empowerment and independence in aspects of health, which in turn, will help participants deal more effectively with the physical and psychosocial complexities of diabetes. TRIAL REGISTRATION: ACTRN12614001085662 . Registered on 10 October 2014.

Body image inflexibility mediates the relationship between body image evaluation and maladaptive body image coping strategies.

Body image inflexibility, the unwillingness to experience negative appearance-related thoughts and emotions, is associated with negative body image and eating disorder symptoms. The present study investigated whether body image inflexibility mediated the relationship between body image evaluation and maladaptive body image coping strategies (appearance-fixing and experiential avoidance) in a college and community sample comprising 156 females aged 18-51 years (M=22.76, SD=6.96). Controlling for recruitment source (college vs. community), body image inflexibility fully mediated the relationship between body image evaluation and maladaptive body image coping strategies. Results indicated that an unwillingness to experience negative appearance-related thoughts and emotions is likely responsible for negative body image evaluation's relationship to appearance-fixing behaviours and experiential avoidance. Findings support extant evidence that interventions that explicitly target body image inflexibility, such as Acceptance and Commitment Therapy, may have utility in treating body dissatisfaction in nonclinical populations.

Smoking, Suicidality and Psychosis: A Systematic Meta-Analysis.

The aim of this study is to systematically review the literature that explored the association between smoking and suicidal risk among those with serious mental illness and to estimate the risk of suicidal behaviors attributable to smoking among this patient group. Multiple databases (CINAHL, PsycINFO, EMBASE, Informit Health Collection and the Cochrane Library databases) were searched from 1 January 1975 through 15 January 2014, along with references from relevant articles for observational studies that ascertained the association between smoking and suicidal behaviors among patients with psychotic disorders conducted in adult patients. Thirteen studies involving 6813 patients with severe mental illness were included. We found that smoking was significantly associated with suicidality in psychosis with an Odds Ratio of 2.12 (95% CI 1.67-2.7). Smoking is associated with suicidal risk amongst individuals with a severe mental illness; however, it is still unclear whether this represents a true risk factor or a confounder or a mediator via mechanisms, hitherto unknown, needs to be studied further.

Classification of eating disorders: comparison of relative prevalence rates using DSM-IV and DSM-5 criteria.

DSM-5 contains substantial changes to eating disorder diagnoses. We examined relative prevalence rates of DSM-IV and DSM-5 eating disorder diagnoses using Eating Disorder Examination-Questionnaire diagnostic algorithms in 117 community out-patients. DSM-5 criteria produced a reduction in combined 'other specified feeding or eating disorder' and 'unspecified feeding or eating disorder' from 46% to 29%, an increase in anorexia nervosa diagnoses from 35% to 47%, the same number of bulimia nervosa diagnoses and a 5% rate of binge eating disorder diagnoses.

A comparison of schizophrenia, schizoaffective disorder, and bipolar disorder: Results from the Second Australian national psychosis survey.

INTRODUCTION: It remains uncertain whether schizoaffective disorder (SAD) is a discrete diagnostic entity, is a variant of either a psychotic mood disorder such as bipolar disorder (BDP) or schizophrenia (SCZ), or exists on a spectral continuum between these disorders. The present study examined whether SCZ, SAD, and BDP differed qualitatively on demographic and clinical variables based on a large Australian dataset. METHODS: This study examined data from the Australian Survey of High Impact Psychosis (SHIP), in which 1469 of the 1825 participants in who had an ICD-10 diagnosis of SCZ (n=857), SAD (n=293), and BDP (n=319) were assessed across a broad range of variables. RESULTS: When compared to patients with SCZ, those with SAD reported more current delusional and thought disorder symptoms, a greater number of lifetime depression, mania, and positive symptoms, and fewer negative symptoms. Relative to the BPD group, the SAD group were younger, endorsed more current positive, delusional, and thought disorder symptoms, fewer lifetime mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, and recorded lower premorbid IQ scores. Compared to patients with BPD, those with SCZ were significantly younger, endorsed more current psychotic and hallucination symptoms, fewer lifetime depression and mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, reported more negative symptoms and had lower premorbid IQ and psychosocial functioning scores. LIMITATIONS: Validated psychometric measures of psychotic or mood symptoms were not used. CONCLUSION: This pattern of results is consistent with the conceptualisation of a spectrum of disorders, ranging from BDP at one end, to SAD in the middle, and SCZ at the other end.