The epidemiology of excess mortality in people with mental illness

Objective: To investigate the burden of excess mortality among people with mental illness in developed countries, how it is distributed, and whether it has changed over time. Method: We conducted a systematic search of MEDLINE, restricting our attention to peer-reviewed studies and reviews published in English relating to mortality and mental illness. Because of the large number of studies that have been undertaken during the last 30 years, we have selected a representative cross-section of studies for inclusion in our review. Results: There is substantial excess mortality in people with mental illness for almost all psychiatric disorders and all main causes of death. Consistently elevated rates have been observed across settings and over time. The highest numbers of excess deaths are due to cardiovascular and respiratory diseases. With life expectancy increasing in the general population, the disparity in mortality outcomes for people with mental illness is increasing. Conclusions: Without the development of alternative approaches to promoting and treating the physical health of people with mental illness, it is possible that the disparity in mortality outcomes will persist

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

All-cause mortality among people with serious mental illness (SMI), substance use disorders, and depressive disorders in southeast London: a cohort study

<p>Abstract</p> <p>Background</p> <p>Higher mortality has been found for people with serious mental illness (SMI, including schizophrenia, schizoaffective disorders, and bipolar affective disorder) at all age groups. Our aim was to characterize vulnerable groups for excess mortality among people with SMI, substance use disorders, depressive episode, and recurrent depressive disorder.</p> <p>Methods</p> <p>A case register was developed at the South London and Maudsley National Health Services Foundation Trust (NHS SLAM), accessing full electronic clinical records on over 150,000 mental health service users as a well-defined cohort since 2006. The Case Register Interactive Search (CRIS) system enabled searching and retrieval of anonymised information since 2008. Deaths were identified by regular national tracing returns after 2006. Standardized mortality ratios (SMRs) were calculated for the period 2007 to 2009 using SLAM records for this period and the expected number of deaths from age-specific mortality statistics for the England and Wales population in 2008. Data were stratified by gender, ethnicity, and specific mental disorders.</p> <p>Results</p> <p>A total of 31,719 cases, aged 15 years old or more, active between 2007-2009 and with mental disorders of interest prior to 2009 were detected in the SLAM case register. SMRs were 2.15 (95% CI: 1.95-2.36) for all SMI with genders combined, 1.89 (1.64-2.17) for women and 2.47 (2.17-2.80) for men. In addition, highest mortality risk was found for substance use disorders (SMR = 4.17; 95% CI: 3.75-4.64). Age- and gender-standardised mortality ratios by ethnic group revealed huge fluctuations, and SMRs for all disorders diminished in strength with age. The main limitation was the setting of secondary mental health care provider in SLAM.</p> <p>Conclusions</p> <p>Substantially higher mortality persists in people with serious mental illness, substance use disorders and depressive disorders. Furthermore, mortality risk differs substantially with age, diagnosis, gender and ethnicity. Further research into specific risk groups is required.</p

Predictors of metabolic monitoring among schizophrenia patients with a new episode of second-generation antipsychotic use in the Veterans Health Administration

<p>Abstract</p> <p>Background</p> <p>To examine the baseline metabolic monitoring (MetMon) for second generation antipsychotics (SGA) among patients with schizophrenia in the Veterans Integrated Service Network (VISN) 16 of the Veterans Health Administration (VHA).</p> <p>Methods</p> <p>VISN16 electronic medical records for 10/2002-08/2005 were used to identify patients with schizophrenia who received a new episode of SGA treatment after 10/2003, in which the VISN 16 baseline MetMon program was implemented. Patients who underwent MetMon (MetMon+: either blood glucose or lipid testing records) were compared with patients who did not (MetMon-), on patient characteristics and resource utilization in the year prior to index treatment episode. A parsimonious logistic regression was used to identify predictors for MetMon+ with adjusted odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Out of 4,709 patients, 3,568 (75.8%) underwent the baseline MetMon. Compared with the MetMon- group, the MetMon+ patients were found more likely to have baseline diagnoses or mediations for diabetes (OR [CI]: 2.336 [1.846-2.955]), dyslipidemia (2.439 [2.029-2.932]), and hypertension (1.497 [1.287-1.743]), substance use disorders (1.460 [1.257-1.696]), or to be recorded as obesity (2.052 [1.724-2.443]). Increased likelihood for monitoring were positively associated with number of antipsychotics during the previous year (FGA: 1.434 [1.129-1.821]; SGA: 1.503 [1.290-1.751]). Other significant predictors for monitoring were more augmentation episodes (1.580 [1.145-2.179]), more outpatient visits (1.007 [1.002-1.013])), hospitalization days (1.011 [1.007-1.015]), and longer duration of antipsychotic use (1.001 [1.001-1.001]). Among the MetMon+ group, approximately 38.9% patient had metabolic syndrome.</p> <p>Discussion</p> <p>This wide time window of 180 days, although congruent with the VHA guidelines for the baseline MetMon process, needs to be re-evaluated and narrowed down, so that optimally the monitoring event occurs at the time of receiving a new episode of SGA treatment. Future research will examine whether or not patients prescribed an SGA are assessed for metabolic syndrome following the index episode of antipsychotic therapy, and whether or not such baseline and follow-up monitoring programs in routine care are cost-effective.</p> <p>Conclusion</p> <p>The baseline MetMon has been performed for a majority of the VISN 16 patients with schizophrenia prior to index SGA over the study period. Compared with MetMon- group, MetMon+ patients were more likely to be obese and manifest a more severe illness profile.</p

Life Expectancy at Birth for People with Serious Mental Illness and Other Major Disorders from a Secondary Mental Health Care Case Register in London

Despite improving healthcare, the gap in mortality between people with serious mental illness (SMI) and general population persists, especially for younger age groups. The electronic database from a large and comprehensive secondary mental healthcare provider in London was utilized to assess the impact of SMI diagnoses on life expectancy at birth.People who were diagnosed with SMI (schizophrenia, schizoaffective disorder, bipolar disorder), substance use disorder, and depressive episode/disorder before the end of 2009 and under active review by the South London and Maudsley NHS Foundation Trust (SLAM) in southeast London during 2007-09 comprised the sample, retrieved by the SLAM Case Register Interactive Search (CRIS) system. We estimated life expectancy at birth for people with SMI and each diagnosis, from national mortality returns between 2007-09, using a life table method.A total of 31,719 eligible people, aged 15 years or older, with SMI were analyzed. Among them, 1,370 died during 2007-09. Compared to national figures, all disorders were associated with substantially lower life expectancy: 8.0 to 14.6 life years lost for men and 9.8 to 17.5 life years lost for women. Highest reductions were found for men with schizophrenia (14.6 years lost) and women with schizoaffective disorders (17.5 years lost).The impact of serious mental illness on life expectancy is marked and generally higher than similarly calculated impacts of well-recognised adverse exposures such as smoking, diabetes and obesity. Strategies to identify and prevent causes of premature death are urgently required

Physical health behaviours and health locus of control in people with schizophrenia-spectrum disorder and bipolar disorder: a cross-sectional comparative study with people with non-psychotic mental illness

<p>Abstract</p> <p>Background</p> <p>People with mental illness experience high levels of morbidity and mortality from physical disease compared to the general population. Our primary aim was to compare how people with severe mental illness (SMI; i.e. schizophrenia-spectrum disorders and bipolar disorder) and non-psychotic mental illness perceive their: (i) global physical health, (ii) barriers to improving physical health, (iii) physical health with respect to important aspects of life and (iv) motivation to change modifiable high-risk behaviours associated with coronary heart disease. A secondary aim was to determine health locus of control in these two groups of participants.</p> <p>Methods</p> <p>People with SMI and non-psychotic mental illness were recruited from an out-patient adult mental health service in London. Cross-sectional comparison between the two groups was conducted by means of a self-completed questionnaire.</p> <p>Results</p> <p>A total of 146 people participated in the study, 52 with SMI and 94 with non-psychotic mental illness. There was no statistical difference between the two groups with respect to the perception of global physical health. However, physical health was considered to be a less important priority in life by people with SMI (OR 0.5, 95% CI 0.2-0.9, <it>p </it>= 0.029). There was no difference between the two groups in their desire to change high risk behaviours. People with SMI are more likely to have a health locus of control determined by powerful others (<it>p </it>< 0.001) and chance (<it>p </it>= 0.006).</p> <p>Conclusions</p> <p>People with SMI appear to give less priority to their physical health needs. Health promotion for people with SMI should aim to raise awareness of modifiable high-risk lifestyle factors. Findings related to locus of control may provide a theoretical focus for clinical intervention in order to promote a much needed behavioural change in this marginalised group of people.</p

Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci

Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity

Monitoring and prevalence rates of metabolic syndrome in military veterans with serious mental illness

Background: Cardiovascular disease is the leading cause of mortality among patients with serious mental illness (SMI) and the prevalence of metabolic syndrome-a constellation of cardiovascular risk factors-is significantly higher in these patients than in the general population. Metabolic monitoring among patients using second generation antipsychotics (SGAs)-a risk factor for metabolic syndrome-has been shown to be inadequate despite the release of several guidelines. However, patients with SMI have several factors independent of medication use that predispose them to a higher prevalence of metabolic syndrome. Our study therefore examines monitoring and prevalence of metabolic syndrome in patients with SMI, including those not using SGAs. Methods and Findings: We retrospectively identified all patients treated at a Veterans Affairs Medical Center with diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder during 2005-2006 and obtained demographic and clinical data. Incomplete monitoring of metabolic syndrome was defined as being unable to determine the status of at least one of the syndrome components. Of the 1,401 patients included (bipolar disorder: 822; schizophrenia: 222; and schizoaffective disorder: 357), 21.4% were incompletely monitored. Only 54.8% of patients who were not prescribed SGAs and did not have previous diagnoses of hypertension or hypercholesterolemia were monitored for all metabolic syndrome components compared to 92.4% of patients who had all three of these characteristics. Among patients monitored for metabolic syndrome completely, age-adjusted prevalence of the syndrome was 48.4%, with no significant difference between the three psychiatric groups. Conclusions: Only one half of patients with SMI not using SGAs or previously diagnosed with hypertension and hypercholesterolemia were completely monitored for metabolic syndrome components compared to greater than 90% of those with these characteristics. With the high prevalence of metabolic syndrome seen in this population, there appears to be a need to intensify efforts to reduce this monitoring gap

Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance