Causes of the excess mortality of schizophrenia

Brown, Sarah; Inskip, Hazel; Barraclough, B. M.

doi:10.1192/bjp.177.3.212

Cited by 962 publications

(608 citation statements)

References 20 publications

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“…Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Section: Introductionmentioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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“…Compared to the general population, people with schizophrenia have increased risks of developing cardiovascular disease (CVD) and type 2 diabetes (T2DM) (Brown et al, 2000;Ryan and Thakore, 2002;Susce et al, 2005), and their life expectancy is shorter by 15 years primarily because of coronary heart disease (Hennekens et al, 2005). Two important factors contributing to this increased morbidity and mortality are inherent susceptibility and antipsychotic medication side effects.…”

Section: Introductionmentioning

confidence: 99%

Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects

Graham

Cho

Brownley

et al. 2008

Schizophrenia Research

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Objective-To examine prospective changes in cardiovascular disease (CVD) and type-2 diabetes risk factors in young adult first episode psychotic (FEP) patients treated with second generation antipsychotic medications.Methods-At baseline, fasting serum and anthropometric measures were obtained from 45 FEP patients and 41 healthy adults (controls) of similar age, ethnicity and sex; sixteen of the FEP patients remained on the same antipsychotic medication and were available for a second blood draw at 24 weeks of treatment. Serum was assayed for glucose, insulin, triglycerides, total cholesterol and high and low density lipoproteins (HDL, LDL), adiponectin, leptin, interleukin 6, E-selectin and VCAM-1. Wilcoxon nonparametric tests were used to compare risk markers between the FEP and control group at baseline and to evaluate pre-post treatment changes within the FEP group.Results-At baseline, the distributions of risk marker values were similar between the two groups and the percentages of FEP patients and healthy controls who were overweight/obese, dyslipidemic, hyperglycemic, and hyperinsulinemic did not differ. At 24 weeks, compared to baseline, FEP patients showed significant increases in BMI (p=0.0002), glucose (p=0.0449), insulin (p=0.0161), cholesterol (p=0.0129), leptin (p=0.0215), and E-selectin (p=0.0195), and a decrease in adiponectin (p=0.0371).Conclusions-Among patients with first episode psychosis, 6-month treatment with second generation antipsychotics is associated with the exacerbation of pre-existing and emergence of new CVD and diabetes risk factors.

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“…Individuals with schizophrenia and other serious mental illnesses (SMI) have a mortality rate at least two times as high as those without SMI, with the excess mortality largely attributed to higher rates of death from cardiovascular disease (CVD) (Brown et al, 2000;Colton and Manderscheid, 2006;Osby et al, 2000). Consistent with this observation are findings of significantly elevated ten-year coronary heart disease risk in individuals with SMI , which is likely a consequence of this population's high rates of Type 2 diabetes (Dixon et al, 2000), metabolic syndrome (Kreyenbuhl et al, 2006;McEvoy et al, 2005), and other cardiovascular risk factors, such as obesity (Daumit et al, 2003), physical inactivity , poor nutrition (McCreadie, 2003), and cigarette smoking (de Leon et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Use of medications to reduce cardiovascular risk among individuals with psychotic disorders and Type 2 diabetes

Kreyenbuhl

Medoff

Seliger

et al. 2008

Schizophrenia Research

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Objective-Cardiovascular disease (CVD) is the leading cause of death in patients with serious mental illness (SMI) and in patients with Type 2 diabetes. Inadequate pharmacologic care for CVD may partially explain poor health outcomes in individuals with both conditions. We sought to identify patients in this group at greatest risk for suboptimal pharmacologic management.Methods-Among individuals with Type 2 diabetes and SMI identified from Maryland Medicaid data, we evaluated patient and service utilization factors associated with the prescription of HMGCoA reductase inhibitors ("statins") for hyperlipidemia and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for chronic kidney disease, congestive heart failure, and hypertension. Results-From 2001 to 2003, the annual prevalence of use of statins and ACE-inhibitors/ARBs ranged from 44-59%, with rates increasing each year. Being female, having certain cardiovascular conditions, and having a greater number of outpatient visits for diabetes increased the odds of receiving statins and ACE-inhibitors/ARBs. More frequent contact with the mental health system was associated with a lower likelihood of receipt of both medication classes; having a substance use disorder was associated with reduced use of statins. African-Americans were less likely than Caucasians to receive statins, but more likely to receive prescriptions for ACE-inhibitors/ARBs.Conclusions-Although use of cardioprotective medications in individuals with Type 2 diabetes and SMI increased over the study period, a considerable proportion of patients remained inadequately managed despite their considerable cardiac risk. Further study should focus on observed racial variations and strategies to increase the capacity of mental health contacts to improve prescribing of these agents.

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Causes of the excess mortality of schizophrenia

Abstract: Some of the excess mortality of schizophrenia could be lessened by reducing patients' smoking and exposure to other environmental risk factors and by improving the management of medical disease, mood disturbance and psychosis.

Cited by 962 publications

References 20 publications

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects

Use of medications to reduce cardiovascular risk among individuals with psychotic disorders and Type 2 diabetes

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