Excess mortality from chronic physical disease in psychiatric patients - The forgotten problem

The article discusses various reports published within the issue, including one by David Lawrence and Joanne Pais on the mortality rate of mentally ill, another by Chris J. Busche and Richard Hodgson on cancer complexities, and on the incidence of chronic disorders among Canadians

Five-year mortality in a cohort of people with schizophrenia in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is associated with a two to three fold excess mortality. Both natural and unnatural causes were reported. However, there is dearth of evidence from low and middle income (LAMIC) countries, particularly in Africa. To our knowledge this is the first community based report from Africa.</p> <p>Methods</p> <p>We followed a cohort of 307 (82.1% males) patients with schizophrenia for five years in Butajira, rural Ethiopia. Mortality was recorded using broad rating schedule as well as verbal autopsy. Standardized Mortality Ratio (SMR) was calculated using the mortality in the demographic and surveillance site as a reference.</p> <p>Result</p> <p>Thirty eight (12.4%) patients, 34 men (11.1%) and 4 women (1.3%), died during the five-year follow up period. The mean age (SD) of the deceased for both sexes was 35 (7.35). The difference was not statistically significant (p = 0.69). It was 35.3 (7.4) for men and 32.3 (6.8) for women. The most common cause of death was infection, 18/38 (47.4%) followed by severe malnutrition, 5/38 (13.2%) and suicide 4/38 (10.5%). The overall SMR was 5.98 (95% CI = 4.09 to7.87). Rural residents had lower mortality with adjusted hazard ratio (HR) of 0.30 (95% CI = 0.12-0.69) but insidious onset and antipsychotic treatment for less than 50% of the follow up period were associated with higher mortality, adjusted HR 2.37 (95% CI = 1.04-5. 41) and 2.66(1.054-6.72) respectively.</p> <p>Conclusion</p> <p>The alarmingly high mortality observed in this patient population is of major concern. Most patients died from potentially treatable conditions. Improving medical and psychiatric care as well as provision of basic needs is recommended.</p

Changes in body weight, body composition and cardiovascular risk factors after long-term nutritional intervention in patients with severe mental illness: an observational study

<p>Abstract</p> <p>Background</p> <p>Compared with the general population, individuals with severe mental illness (SMI) have increased prevalence rates of obesity and greater risk for cardiovascular disease. This study aimed to investigate the effects of a long term nutritional intervention on body weight, body fat and cardiovascular risk factors in a large number of patients with SMI.</p> <p>Methods</p> <p>Nine hundred and eighty-nine patients with a mean ± S.D age of 40 ± 11.7 yrs participated in a 9 mo nutritional intervention which provided personalised dietetic treatment and lifestyle counselling every two weeks. Patients had an average body mass index (BMI) of 34.3 ± 7.1 kg.m^-2and body weight (BW) of 94.9 ± 21.7 kg. Fasted blood samples were collected for the measurement of glucose, total cholesterol, triglycerides and HDL- cholesterol. All measurements were undertaken at baseline and at 3 mo, 6 mo and 9 mo of the nutritional intervention.</p> <p>Results</p> <p>Four hundred and twenty-three patients of 989 total patients' cases (42.8%) dropped out within the first 3 months. Two hundred eighty-five completed 6 months of the program and 145 completed the entire 9 month nutritional intervention. There were progressive statistically significant reductions in mean weight, fat mass, waist and BMI throughout the duration of monitoring (p < 0.001). The mean final weight loss was 9.7 kg and BMI decreased to 30.7 kg.m^-2(p < 0.001). The mean final fat mass loss was 8.0 kg and the mean final waist circumference reduction was 10.3 cm (p < 0.001) compared to baseline. Significant and continual reductions were observed in fasting plasma glucose, total cholesterol and triglycerides concentrations throughout the study (p < 0.001).</p> <p>Conclusion</p> <p>The nutritional intervention produced significant reductions in body weight, body fat and improved the cardiometabolic profile in patients with SMI. These findings indicate the importance of weight-reducing nutritional intervention in decreasing the cardiovascular risk in patients with SMI.</p

Co-expression network of neural-differentiation genes shows specific pattern in schizophrenia

Background: Schizophrenia is a neurodevelopmental disorder with genetic and environmental factors contributing to its pathogenesis, although the mechanism is unknown due to the difficulties in accessing diseased tissue during human neurodevelopment. The aim of this study was to find neuronal differentiation genes disrupted in schizophrenia and to evaluate those genes in post-mortem brain tissues from schizophrenia cases and controls. Methods: We analyzed differentially expressed genes (DEG), copy number variation (CNV) and differential methylation in human induced pluripotent stem cells (hiPSC) derived from fibroblasts from one control and one schizophrenia patient and further differentiated into neuron (NPC). Expression of the DEG were analyzed with microarrays of post-mortem brain tissue (frontal cortex) cohort of 29 schizophrenia cases and 30 controls. A Weighted Gene Co-expression Network Analysis (WGCNA) using the DEG was used to detect clusters of co-expressed genes that werenon-conserved between adult cases and controls brain samples. Results: We identified methylation alterations potentially involved with neuronal differentiation in schizophrenia, which displayed an over-representation of genes related to chromatin remodeling complex (adjP = 0.04). We found 228 DEG associated with neuronal differentiation. These genes were involved with metabolic processes, signal transduction, nervous system development, regulation of neurogenesis and neuronal differentiation. Between adult brain samples from cases and controls there were 233 DEG, with only four genes overlapping with the 228 DEG, probably because we compared single cell to tissue bulks and more importantly, the cells were at different stages of development. The comparison of the co-expressed network of the 228 genes in adult brain samples between cases and controls revealed a less conserved module enriched for genes associated with oxidative stress and negative regulation of cell differentiation. Conclusion: This study supports the relevance of using cellular approaches to dissect molecular aspects of neurogenesis with impact in the schizophrenic brain. We showed that, although generated by different approaches, both sets of DEG associated to schizophrenia were involved with neocortical development. The results add to the hypothesis that critical metabolic changes may be occurring during early neurodevelopment influencing faulty development of the brain and potentially contributing to further vulnerability to the illness.We thank the patients, doctors and nurses involved with sample collection and the Stanley Medical Research Institute. This research was supported by either Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq #17/2008) and Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). MM (CNPq 304429/2014-7), ACT (FAPESP 2014/00041-1), LL (CAPES 10682/13-9) HV (CAPES) and BP (PPSUS 137270) were supported by their fellowshipsinfo:eu-repo/semantics/publishedVersio

The effects of lifestyle interventions on (long-term) weight management, cardiometabolic risk and depressive symptoms in people with psychotic disorders:A meta-analysis

AIMS: The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. MATERIAL AND METHODS: We searched four databases for randomized controlled trials (RCTs) that compared lifestyle interventions to control conditions in patients with psychotic disorders. Lifestyle interventions were aimed at weight loss or weight gain prevention, and the study outcomes included bodyweight or metabolic parameters. RESULTS: The search resulted in 25 RCTs -only 4 were considered high quality- showing an overall effect of lifestyle interventions on bodyweight (effect size (ES)  =  -0.63, p<0.0001). Lifestyle interventions were effective in both weight loss (ES =  -0.52, p<0.0001) and weight-gain-prevention (ES =  -0.84, p = 0.0002). There were significant long-term effects, two to six months post-intervention, for both weight-gain-prevention interventions (ES =  -0.85, p = 0.0002) and weight loss studies (ES =  -0.46, p = 0.02). Up to ten studies reported on cardiometabolic risk factors and showed that lifestyle interventions led to significant improvements in waist circumference, triglycerides, fasting glucose and insulin. No significant effects were found for blood pressure and cholesterol levels. Four studies reported on depressive symptoms and showed a significant effect (ES =  -0.95, p = 0.05). CONCLUSION: Lifestyle interventions are effective in treating and preventing obesity, and in reducing cardiometabolic risk factors. However, the quality of the studies leaves much to be desired

Efficacy of atomoxetine in adults with attention deficit hyperactivity disorder: An integrated analysis of the complete database of multicenter placebo-controlled trials

Persistence of attention deficit hyperactivity disorder (ADHD) into adulthood can be disabling or lead to substantial impairment. Several clinical trials of atomoxetine (ATX) in adults with ADHD have been reported following the National Institute for Health and Clinical Excellence (NICE) guidelines issued in 2008. We performed an integrated analysis of all Eli Lilly-sponsored, randomized, double-blind, placebo-controlled studies of ATX in adults with ADHD completed as of May 2012. Individual patient data were pooled from six short-term (10–16 week) studies (1961 patients) and three longer-term (six-month) studies (1413 patients). In the short-term analysis, ATX patients achieved a significantly greater mean reduction in ADHD symptoms than placebo patients (−12.2 vs −8.1; Conners’ Adult ADHD Rating Scale–Investigator-Rated: Screening Version (CAARS-Inv: SV); p<0.001). In the longer-term analysis, respective improvements after six months were −13.2 vs −9.7 (p<0.001). Response rates at study endpoints for ATX vs placebo, based on CAARS-Inv: SV improvement ≥30% and Clinical Global Impressions of ADHD-Severity (CGI-ADHD-S) ≤3 were 34.8% vs 22.3% in the short-term and 43.4% vs 28.0% after six months, and CAARS-Inv: SV improvements ≥40% were 41.3% vs 25.3% in the short-term and 44.0% vs 31.4% after six months (all p<0.001). Overall, ATX had a clinically significant effect in adults with ADHD, with reductions in core symptoms and clinically meaningful responder rates