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Metabolic profile and indices in a sample of drug-naive patients with schizophrenia and bipolar disorder

Zaki, Nivert; Sadek, Hisham; Hewedi, Doaa; Hamed, Hani; Raafat, Omnia

Middle East Current Psychiatry: January 2014 - Volume 21 - Issue 1 - p 22–27
doi: 10.1097/01.XME.0000438128.94669.57
Original articles
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Background Patients with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome (MetS) and its components, risk factors for cardiovascular disease, and type 2 diabetes. Although the prevalence of obesity and other risk factors such as hyperglycemia are increasing in the general population, patients with major mental illnesses have an increased prevalence of overweight and obesity, hyperglycemia, dyslipidemia, hypertension, and smoking, and considerably greater mortality compared with the general population.

Objectives The main objective of this study is to determine the development of MetS in a sample of drug-naive patients with schizophrenia and bipolar affective disorders compared with a matched control group and to identify the significant criteria and risk factors of developing MetS.

Patients and methods This was a cross-sectional case–control study in which 60 participants were recruited, 40 with the diagnosis of schizophrenia and bipolar affective disorders and 20 matched control ones selected from inpatient units and outpatient psychiatric clinics at the Institute of Psychiatry, Ain Shams University, over a period of 6 months. The recruited samples were assessed by a semistructured interview on the basis of the interview (questionnaire) sheet of the Institute of Psychiatry, Ain Shams University Hospital, and the diagnosis was made on the basis of the International Classification of Diseases-10 symptom checklist with an established diagnosis of acute psychosis. They were also assessed by the following measurements: blood pressure, body weight, circumference, laboratory investigations including assessment of fasting blood glucose level, using oral glucose tolerance test, lipid profile including assessment of triglyceride, cholesterol, and high-density lipoprotein level.

Results The results for the clinical and laboratory profile of the three participant groups showed a highly significant correlation between fulfillment of the criteria of MetS and the pathology of psychotic and bipolar affective disorders. Moreover, the presence of positive risk factors for development of MetS was found to be significantly high among the two patient groups compared with the control one.

Conclusion Schizophrenic and bipolar drug-naive patients are more likely to develop metabolic changes; our results support the need for close monitoring of metabolic abnormalities and preferential use of metabolic neutral agents in this population as the first-line treatment option. Further research focusing on elucidation of the complicated relationship between metabolic disorders and psychiatric conditions may enable the development of earlier effective interventions.

aDepartment of Neuropsychiatry, Faculty of Medicine, Institute of Psychiatry, Ain Shams University

bDepartment of Psychiatry, Faculty of Medicine, Cairo University, Cairo

cDepartment of Psychiatry, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt

Corresponding to Nivert Zaki, MD, Department of Neuropsychiatry, Faculty of Medicine, Institute of Psychiatry, Ain Shams University, Abbasia Square, PO Box 22, Dair El Malak, Cairo 11657, Egypt Tel: +20 100 517 1881; fax: +20 222 683 6379/22 683 0459; e-mail: nivertzaki@yahoo.com

Received September 22, 2012

Accepted October 20, 2013

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Introduction

Metabolic syndrome (MetS) is a group of disorders including obesity (both central and abdominal), hypertension, dyslipidemia, glucose intolerance, and insulin resistance 1. MetS is associated with a four times higher risk of developing diabetes 2 and a three times higher risk of dying from coronary heart disease 3. The term ‘metabolic syndrome’ was introduced in 1998 and used by a number of organizations 4,5. Individuals with severe mental illness are more likely to be overweight, to smoke, and to have hyperglycemia/diabetes, hypertension, and dyslipidemia 6. It is generally estimated that MetS is especially common in patients with severe mental illness, with a high prevalence ranging from 30 to 60% for schizophrenic and bipolar disorders 7. Between 25% (Spain) 8 and 41% (USA) of patients with schizophrenia have MetS. This is a much higher prevalence than in comparable general populations 9. The higher prevalence of MetS in patients with schizophrenia may be explained by medication-related, disease-related, and lifestyle-related factors. Second-generation antipsychotic (SGA) drugs cause dyslipidemia, weight gain, and diabetes to a varying extent 10. A high prevalence of diabetes was found in drug-naive schizophrenic patients 11 and in parents of patients with psychotic diseases 12. The link between various mental illnesses and different components of MetS is becoming clearer 13. In the psychiatric community, this has led in recent years to a growing concern about physical illness in individuals with severe mental illness, specifically the risk of cardiovascular disorders 14. It is essential to study the link between components of MetS, especially modifiable components, with physical and medical illnesses in mentally ill patients 13.

The study was carried out with the aim to screen the rate of metabolic profile among a sample of drug-naive patients with schizophrenia and bipolar affective disorders compared with a matched control group to determine the development of MetS in a sample of drug-naive patients with schizophrenia and bipolar affective disorders compared with a matched control group and to identify the significant criteria and risk factors of developing MetS including family history of psychiatric disorder, family history of medical disorder, type of previous psychotropic drugs, smoking, fatty diet, and physical activities among the studied participants.

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Patients and methods

The study was carried out as a cross-sectional case–control study at the Institute of Psychiatry, Ain Shams University, over a 6-month period from the start of July 2011 till the end of December 2011. Patients were selected randomly from inpatient units and outpatient psychiatric clinics. Two groups, with each group including 20 patients, were recruited as they fulfilled the criteria of drug-free schizophrenia for the last year in the first group or drug-free bipolar affective disorder with or without psychotic features in the last year as the second group according to the International Classification of Diseases-10 (ICD-10) checklist during their admission to the institute according to the following inclusion criteria: (a) age between 15 and 55 years and (b) drug naive (i.e. never took any psychiatric medication before) or/and neuroleptic drug free for at least 1 year before beginning of the study. They were selected irrespective of their sex, socioeconomic, or educational status. Exclusion criteria included patients who were on psychotropic medications during the last year or had any history of comorbid medical diseases. These were compared with 20 healthy volunteers who were matched with the case group in terms of age, sex, and sociodemographic variables. They had no history of any psychiatric or medical problems, and were recruited from among employees working at the Institute of Psychiatry, Ain Shams University. Patients were informed of the research and were examined immediately following their admission.

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Ethical consideration

Ethical approval for the study was provided by the Ain Shams University Ethical and Research Committee. An informed consent was obtained from all participants after they were informed about the details of the study and that venous blood samples will be collected. Patients were ensured about the confidentiality of information. Participation in the study was completely voluntary, and patients were informed that they could withdraw from the assessment at any time. Moreover, they were informed that withdrawal from the study would not affect their management.

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Procedures

The patients were assessed by a semistructured interview on the basis of the interview (questionnaire) sheet of the Institute of Psychiatry, Ain Shams University Hospital, and the diagnosis was made on the basis of the ICD-10 symptom checklist.

The diagnosis of MetS and its components was made on the basis of the International Diabetes Federation (IDF) criteria 15. Although it appears that the IDF definition for MetS is not much different from other organizations’ definitions, it is much more applicable for use in various studies and researches than other definitions as it is more clinically applicable and easy to apply 16. Baseline evaluation of blood pressure (BP) using a single mercury BP monitor and laboratory investigations for the three groups were performed before antipsychotic medications were provided for the two case groups and as an initial assessment of the participants studied.

The three groups were subjected to the following assessments:

(a) Subsequent BP monitoring at the same time each day, (b) measurement of anthropometric variables, waist circumference (WC) monitoring, and BMI on the basis of weight and height (kg/m2) 17,18, and (c) laboratory investigations including assessment of fasting blood glucose (FBG), using the oral glucose tolerance test, which was performed if the results of FBG were above 100 mg/dl, and lipid profile including assessment of triglyceride (TG), cholesterol, and high-density lipoprotein (HDL) level. Interpretation of the oral glucose tolerance test was carried out on the basis of the 1999 WHO Diabetes criteria 19. Elevated BP was defined when BP was more than 130/85 mmHg, abdominal obesity (WC: women>88 cm, men>102 cm), low HDL level (women<1.3 mmol/l, men<1.03 mmol/l), and high TG level (1.7 mmol/l) 20.

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Statistical analysis

The results were analyzed using the statistical package for the social science (SPSS; version number 15; Echosoft Corp., USA). Description of quantitative variables was in the form of mean±SD and range whereas that of qualitative variables was in the form of frequency and percentage. Student’s t-test of two independent samples was used to compare quantitative variables; paired Student’s t-test and one-way analyses of variance were used. Significance was set at 0.05. When the P value was less than 0.05, the test was considered significant.

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Results

Sample description

In our study, 20 patients [13 (65%) men and seven (35%) women] with schizophrenia, mean age 36.9 (SD=8.8), 20 patients [16 (80%) men and four (20%) women] with bipolar affective disorder, mean age 36.8 (SD=8.5), and 20 controls [13 (65%) men and seven women (35%)], mean age 36.8 (SD=8.7), were recruited.

Table 1 shows descriptively the sociodemographic profile of the participants recruited.

Table 1

Table 1

Table 2 shows a high and a very high significant difference between the three participant groups. Body weight, WC, BP, FBG, total cholesterol, and TG levels were found to be significantly high among the two groups of patients with schizophrenia and bipolar disorders compared with the control group, whereas HDL levels among the two patients groups were significantly lower compared with the control group.

Table 2

Table 2

Table 3 shows that the risk factors of having MetS including a positive family history of medical disease, being a smoker, no regular physical activity, and previous intake of antipsychotic drugs were significantly high among the patient groups with schizophrenia and bipolar disorders than the control group, whereas other risk factors such as a positive family history of psychiatric illness or a fatty diet showed no significant difference among the three participant groups.

Table 3

Table 3

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Discussion

Monitoring for MetS, a major modifiable risk factor for cardiovascular mortality, is paramount for the early detection and management of many medical problems in psychiatric patients. As previous studies have focused solely on psychiatric patients using SGAs, our study investigated current monitoring of MetS in a sample of patients with serious mental illness, including patients not using antipsychotic medications, with a focus on monitoring the risk factors of developing MetS. This was a cross-sectional case–control study in which 20 patients, 13 (65%) men and seven (35%) women with schizophrenia, mean age 36.9 (SD=8.8), 20 patients, 16 (80%) men and four (20%) women with bipolar affective disorder, mean age 36.8 (SD=8.5), and 20 controls, 13 (65%) men and seven women (35%), mean age 36.8 (SD=8.7), were recruited.

On monitoring the quantitative clinical and laboratory profiles among the schizophrenic, bipolar, and control groups, there was a significant difference between the three participant groups in body weight and WC. Bipolar and schizophrenic patients were more significantly obese than the control ones. This can be attributed to poor lifestyle factors that are commonly found in mentally ill patients such as physical inactivity, poor dietary habits, smoking, and drinking. This is in agreement with Kraemer et al. 21, who found an increase in WC in psychotic patients than in the control group. McLaren and Marangell 22 reported that disease-specific symptoms and behaviors, particularly those that occur during depressive episodes, such as increased appetite, decreased physical activity, and reduced energy expenditure, increase the risk for obesity. Hatata et al.23 found that increased WC and higher BMI were significant predictors of MetS in the sample. Thirty-nine (61.91%) patients did not fulfill all the criteria for the syndrome; however, 31 of these 39 patients (49.2%) fulfilled 1–2 criterion of the syndrome. The FBG level was significantly higher in both schizophrenic and bipolar groups than the control group. Chronic stress, which patients experience during both the manic and the depressive phases of bipolar disorder, is associated with increased cortisol levels, lack of cortisol suppression, and changes in hypothalamic–pituitary–adrenal axis responses. This metabolic dysregulation may increase insulin resistance and can lead to hyperglycemia, increased oxidative stress, and MetS. First-episode patients did not show a higher prevalence of the precursors to diabetes, that is, impaired FBG, impaired glucose tolerance, and insulin resistance, compared with healthy controls 24. A study comparing baseline metabolic parameters in drug-naive schizophrenia patients and healthy controls (n=26 in each group) reported that the patients had significantly higher FBG and insulin levels, and were more insulin resistant 25. The cholesterol and TG levels in both schizophrenic and bipolar patients were significantly higher than those in the healthy controls. HDL levels among the two patient groups were significantly lower compared with the control group. Kraemer et al.21 found that TG levels were significantly higher in the psychotic group compared with those without psychosis. Also, HDL levels were significantly lower in patients with psychosis compared with those without psychosis. Zhang et al.26 reported that there were no differences in FBG, insulin, and lipid profile between drug-naive first-episode schizophrenia patients and healthy controls (46 patients and 38 controls in each group). Sengupta et al.24 found no significant difference in β-cell function or lipid profile measures in first-episode psychotic patients compared with healthy controls.

Assessment of risk factors for MetS showed that there was a significant difference in the positive family history of medical illness in both schizophrenic and bipolar patients in comparison with the controls, with no significant difference in a positive psychiatric family history. This can be attributed to the underlying genetic risk for the development of metabolic abnormalities and emphasized that future studies will need to address possible gene–environment interactions with specific antipsychotic agents 27. Thakore 1 reported that older researches have shown an increased risk of patients with schizophrenia to develop metabolic abnormalities in the absence of antipsychotic medication, and there are indications of an increased risk for diabetes in first-degree relatives. Verma et al.28 explored the underlying genetic risk for the development of metabolic abnormalities. The link between diabetes and psychotic illness reported previously in relatives of patients with schizophrenia and in medication-naive patients implies a possible genetic link between schizophrenia and abnormal glucose metabolism. There were more smokers among both schizophrenic and bipolar patients than controls, with a significant difference. This could be attributed to their sedentary life and irritability. Also, the significant difference between the three study groups in physical activity can be explained by their negative symptoms and their overweight. Scheen and De Hert 29 found that patients with schizophrenia on average have a lifestyle that increases their risk for the development of MetS: sedentary lifestyle, lack of regular physical activity, and high rates of smoking. Ellingrod et al.27 found that MetS was related to age and smoking.

Our results indicate that previous intake of antipsychotic drugs was significantly high among patients groups with schizophrenia and bipolar disorders rather than the control group. This is in agreement with Corell et al.17, who found that patients with bipolar disorder and schizophrenia treated with SGAs have similarly high rates of MetS. These findings suggest a shared susceptibility to antipsychotic-related metabolic dysregulations that is not primarily related to a psychiatric diagnosis or concomitant mood stabilizer treatment.

Over recent years, it has become apparent that antipsychotic agents can have a negative impact on some of the modifiable risk factors. Part of this negative impact can be explained by the potential of some antipsychotics to induce significant weight gain. A recent study indicates that these metabolic changes are dose independent 14. Verma et al.28 found a low prevalence of obesity and dyslipidemia at the onset of illness in their patients and suggested that the increased frequency of these abnormalities in patients is an effect of their antipsychotic medication 27. Our study expands on the existing literature by monitoring all five MetS components among patients with different psychiatric disorders, especially those not using SGAs. Our results show that body weight, WC, FBG, total cholesterol, and TG levels were found to be significantly high among the two groups of patients with schizophrenia and bipolar disorders compared with the control group, whereas HDL levels among the two patients groups were significantly lower compared with the control group. These results, coupled with the high prevalence of MetS – more than double that of the general population as reported in the Corell et al.17 studies, suggest a need to intensify monitoring of MetS among all patients with serious mental illness, including for those not using SGAs.

However, this clarifies how important the actual monitoring of vital signs and blood values is in patients with schizophrenia and bipolar disorder, as seemingly, a large proportion of these patients were neither aware of their somatic health status nor adequately diagnosed and treated for cardiovascular risk factors.

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Conclusion

Schizophrenic and bipolar drug-naive patients are more likely to develop metabolic changes; our results support the need for close monitoring of metabolic abnormalities and preferential use of metabolic neutral agents in this population as the first-line treatment option. Further research focusing on elucidating the complicated relationship between metabolic disorders and psychiatric conditions may enable the development of earlier effective interventions.

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Clinical implications

MetS and other cardiovascular risk factors are highly prevalent in individuals with schizophrenia and bipolar affective disorders. Patients are at risk for premature mortality and overall have limited access to physical healthcare. In part, these cardiometabolic risk factors are attributable to an unhealthy lifestyle, including a poor diet and a sedentary life. In our study, it is apparent that a psychiatric pathology can have a negative impact on some of the modifiable risk factors. The psychiatrist needs to be aware of those potential risk factors and to include them in the risk/benefit assessment when choosing a specific antipsychotic. In addition, they should also be responsible for the implementation of the necessary screening assessments and referral for treatment of any physical illness. Multidisciplinary assessment of psychiatric and medical conditions is needed. The somatic treatments offered to individuals with severe and enduring mental illness should be in collaboration with general healthcare in the nonpsychiatrically ill population. Moreover, psychiatrists should screen for such metabolic disturbances if patients have no access to primary care. Finally, simple lifestyle advice on the benefits of a balanced diet and regular exercise should be routinely provided to all patients, as these are still the most effective ways of preventing diabetes and its related complications.

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Limitations

Although our study showed a significant correlation between the presence of schizophrenia and bipolar affective disorders pathology and the development of MetS, and although it has been carried out on 40 patients with both disorders, further studies should be carried out on a larger scale not only on drug-naive patients with schizophrenia or bipolar disorders but also on patients fulfilling the criteria of the entire psychotic spectrum to obtain more significant results and implementations.

Figure

Figure

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

bipolar disorder; metabolic syndrome; schizophrenia

© 2014 Institute of Psychiatry, Ain Shams University