|Year : 2013 | Volume
| Issue : 5 | Page : 890-895
Association of metabolic syndrome with schizophrenia
Sarita Bajaj, Anurag Varma, Anubha Srivastava, Anand Kumar Verma
Department of Medicine, M.L.N. Medical College, Allahabad, India
|Date of Web Publication||29-Aug-2013|
Department of Medicine, Psychiatry Unit, M.L.N. Medical College, Allahabad - 211 001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Metabolic syndrome (MetS) is associated with mental illnesses. It is a major predictor of mortality and morbidity in patients of such mental illnesses. This study was undertaken to study the association of MetS and schizophrenia. Objectives: To study the association of MetS in patients of schizophrenia. Materials and Methods: Adult schizophrenic patients diagnosed as per Diagnostic and Statistical Manual -IV Third R evisioncriteria visiting the psychiatric Out Patient Day during the study period were evaluated for prevalence of MetS as per the criteria of the international diabetes federation. Fifty patients of schizophrenia with age-and sex-matched 50 controls were enrolled for the study. Results: MetS was found to be 28% in patient group and 12% in control group (P < 0.05). Fourteen patients were found to have MetS out of 38 patients who were on antipsychotics for >6 months. All the 14 patients having MetS were taking second-generation antipsychotics (SGAs) ( P < 0.05). Conclusion: The study showed a higher prevalence of MetS in schizophrenia than in general population. MetS was present only in patients taking SGAs and prevalence of MetS had a positive correlation with duration of treatment. The study points toward urgent need for consultation - liaisoning between Diabetologist and Psychiatrists.
Keywords: Metabolic syndrome, schizophrenia, second-generation antipsychotics
|How to cite this article:|
Bajaj S, Varma A, Srivastava A, Verma AK. Association of metabolic syndrome with schizophrenia. Indian J Endocr Metab 2013;17:890-5
|How to cite this URL:|
Bajaj S, Varma A, Srivastava A, Verma AK. Association of metabolic syndrome with schizophrenia. Indian J Endocr Metab [serial online] 2013 [cited 2020 Oct 1];17:890-5. Available from: http://www.ijem.in/text.asp?2013/17/5/890/117238
| Introduction|| |
Psychiatric disorders are associated with increased medical morbidity and mortality that are largely due to treatable medical conditions such as cardiovascular disease (CVD), diabetes, respiratory, and infectious diseases. Recognition and management of medical morbidity in patients with psychiatric illnesses are difficult due to barriers related to the patient, the illness, the attitudes of medical practitioners, and the structure of healthcare delivery services. 
During last several years there has been growing interest in metabolic abnormalities in schizophrenia. These disturbances are highly co-incident and metabolic syndrome (MetS), which is seen in around 3-4% in general population has an incidence of around 10% in schizophrenic patients. MetS is a cluster of risk factor, for CVD comprising of central obesity, dyslipidemia, hypertension, and elevated fasting plasma glucose levels. 
Schizophrenic patients with the MetS have higher rates of coronary heart disease, myocardial infarction, and stroke than the same patients with any one of the components of hypertension, insulin-resistance, dyslipidemia, or obesity. 
The risk of these medical co-morbidities is further increased by the use of psychotropic medications that are used for the treatment of such patients. The risk may be greater with some second-generation antipsychotic (SGA) agents. 
The SGA medications have been associated with weight gain, diabetes, dyslipidemia, insulin resistance, and the MetS.  There are number of studies which have found that the risk of MetS is greater in those receiving psychotropic medications as compared to the general population. Studies in this context are lacking in India. Thus, in this study, prevalence of MetS in patients of schizophrenia was assessed. This is likely to help and have a bearing on choosing appropriate psychotropic medications for these patients and need for multidisciplinary approach for holistic healthcare.
| Materials and Methods|| |
- Known cases of schizophrenia, according to DSM-IV criteria, are selected from the patients who attended psychiatric OPD in our hospital
- Age: 18-50 years
- Informed consent was obtained in written and the institutional ethical committee's permission was obtained.
- The control group comprised of age-and sex-matched volunteers.
- Presence of diagnosed medical disorders such as coronary artery disease, hypothyroidism, nephrotic syndrome, liver disorders, etc
- Patients suffering from any other chronic psychiatric illness
- Pregnancy, lactation and use of oral contraceptive pills.
This study is a cross-sectional study of 100 subjects, of which 50 patients are schizophrenics and remaining 50 are age- and sex-matched controls.
During the period of study, 50 out of 62 patients of schizophrenia screened fulfilled the selection criteria. Similarly 50 out of 58 age-and sex-matched healthy volunteer controls fulfilled the selection criteria. Excel (Microsoft Office 2007) and statistical package for social sciences software packages were used for data entry and analysis and significance level of P < 0.05 [Figure 1].
|Figure 1: Profile of patients enrolled in the study to assess the relation of schizophrenia and second-generation antipsychotic|
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| Results|| |
Fourteen (28%) patients in schizophrenia group (n = 50) and six (12%) subjects in control group (n = 50) had MetS.
Socio-demographic profile of cases and controls
Statistically significant difference was found in domicile and education of the patient in the patient group when compared with the control group. Number of subjects residing in urban area was more in control group and was more educated as compared to patient group. Among patient group, majority of subjects were residing in rural area and were educated upto 10 th class. There was no significant difference observed in religion, marital status, and socio-economic status of patient and control groups [Table 1].
Risk factor profile of cases and controls
The mean values of serum triglyceride were higher than normal range in patient group and within normal range in control group. There was statistically significant difference in mean serum triglyceride of patient and control groups. The mean serum triglyceride of schizophrenia (153.41 ± 57.26) was significantly higher (P < 0.05) as compared to control group (127.94 ± 30.88) [Table 2].
Comparison of clinical variables of patients having metabolic syndrome and patients without metabolic syndrome [Table 3]
|Table 3: Comparison of clinical variables of patients having metabolic syndrome and patients without metabolic syndrome|
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MetS was associated in patients with longer duration of illness (DOI), but this did not reach a statistically significant level.
Duration of taking antipsychotics between patients having MetS to those without MetS was statistically significant.
Statistically significant difference was found between both the patient groups who were taking first- and second-generation antipsychotics (SGAs).
No. of patients on haloperidol - 6.-No MetS.
No. of patients on trifluperazine - 3.-No MetS.
No. of patients on clozapine - 5.-All having MetS.
No. of patients on olanzapine - 30.-9 having MetS.
No. of patients not taking any drugs - 6.-No MetS.
Comparison of body mass index in patients having metabolic syndrome and patients without metabolic syndrome
The mean body mass index (BMI) was high in patients having MetS and was in normal range in patients without MetS. Mean scores of BMI were significantly higher (i.e., more number of obese patients) in patients having MetS as compared to those without MetS [Table 4].
|Table 4: Comparison of body mass index in patients having metabolic syndrome and patients without metabolic syndrome|
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Comparison of metabolic syndrome parameters in patients having metabolic syndrome and patients without metabolic syndrome
The waist circumference of patients of schizophrenia having MetS (93.60 ± 7.36) was observed to be significantly (P < 0.0001) higher in comparison to those without MetS (77.82 ± 9.33).
The mean fasting blood sugar of patients having MetS was observed to be significantly (P = 0.0054) higher in comparison to those without MetS.
The mean serum triglyceride of patients having MetS was observed to be significantly (P < 0.0001) higher as compared to those without MetS [Table 5].
|Table 5: Comparison of metabolic syndrome parameters in patients having metabolic syndrome and patients without metabolic syndrome|
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| Discussion|| |
In a case-control study of out-patients on antipsychotics versus age-and gender-matched controls, Mackin et al.  found that the prevalence of MetS was 33.3% in schizophrenia group (n = 90) and 11.9% in control group. The study by Mattoo and Singh  in this issue has addressed the problem of MetS in psychiatric inpatients in a hospital scenario. This research is timely considering that there is no prior published work on MetS in psychiatric inpatients in India. The findings of these studies are comparable to this study. In this study, the prevalence of MetS was 28% in schizophrenia group and 12% in control group.
Two studies from north India published during 1994 and 2000 showed a prevalence of obesity 17% (Ludhiana)  and 15% (Kashmir)  respectively. In another study conducted by Martin et al.  had shown that prevalence of obesity was found significantly higher in patients with schizophrenia as compared to control. Similar findings were observed in the study conducted by De Hert et al.  In this study, 19 (38%) patients in schizophrenia group and 18 (36%) in control group have increased waist circumference (i.e., obesity). Mean values of waist circumference in schizophrenia group (82.24 + 11.30) were higher as compared to control group (81.67 + 10.56). However, statistically significant difference was not found.
One study which was conducted in 2002  has shown higher fasting blood glucose in drug-naïve patients of schizophrenia as compared to controls. The study had reported that prevalence of diabetes was 15% higher in patient group as compared to controls. The prevalence of Fastng Blood Sugar (18% schizophrenia and 4% in controls) in patients of this study was significantly higher than the general population. Mean values of fasting blood sugar in schizophrenia group (87.47 + 20.37) were higher as compared to control group (84.83 + 12.50). Statistically significant difference was not observed between control group and schizophrenia.
Study conducted by De Hert et al.  had shown that prevalence of hyperlipidemia was found significantly higher in patients with schizophrenia as compared to control. In this study, 20 (40%) patients in schizophrenia group and 10 (20%) subjects in control group have increased serum triglyceride. Proportion of subjects having increased serum triglyceride was significantly higher ( P < 0.05) in schizophrenia group as compared to control group. Thirty-six (72%) patients in schizophrenia group and 22 (44%) subjects in control group have low serum HDL. Proportion of subjects having low serum HDL was significantly higher ( P < 0.05) in patient group as compared to control group. Also in this study, mean values of serum High Density Lipoprotien in schizophrenia group (40.25 + 7.28) were lower as compared to control group (42.74 + 8.11), but statistically significant difference was not observed. Mean values of serum triglyceride of schizophrenia group (153.41 + 57.26) were significantly higher ( P < 0.05) as compared to control group (127.94 + 30.88).
The study by D J Raina, DS Jamwal  involving 2216 individuals among rural adults of Jammu, prevalence of hypertension was13%; females 14.71%: males 11.19% showing a strong association between gender and hypertension ( P <0.02). (Criteria: ≥140/90 mm of Hg) among males and females, To our best efforts, we are not able to find the studies which could mention about the prevalence of hypertension in psychiatric patients in India in relation to MetS. Comparing these studies with our study showed that 11 (22%) patients in schizophrenia group and 11 (22%) subjects in control group have higher than normal blood pressure (≥130/85 mm Hg). Low incidence of hypertension in both study and control group may be because the sample size was small and relatively younger age group was taken. Mean values of systolic blood pressure (SBP) (123.84 + 11.81) as well as diastolic blood pressure (DBP) (77.12 + 7.68) of schizophrenia group were higher as compared to control group (SBP - 120.32 ± 14.09; DBP - 76.32 ± 9.11). Statistically significant difference was not observed.
Study conducted by Thakore et al.  in 2002 in which they found that patients of schizophrenia have higher BMI (26.7 + 1.1 kg/m 2 ) as compared to controls (23.5 + 0.8 kg/m 2 ). Study conducted by De Hert et al.  has also shown that BMI was higher in patients having MetS and its prevalence increased with increasing DOI. This study also showed that mean values of BMI were found higher in schizophrenia group (22.55 + 4.19) as compared to control group (22.30 + 3.35). Statistically significant differences were not observed.
Geographical and ethnic variation can also account for lower rate of prevalence. Statistically significant difference was observed in domicile and education of schizophrenic group. Patients having MetS belong more in rural area than in urban area and were more educated as compared to patient group. Statistically significant differences were not observed in other socio-demographic variables such as gender, religion, and socio-economic status of both the patient groups. The possible reasons for this finding may be small sample size.
Although studies have not mentioned directly about relationship of age with MetS, but it has been postulated that prevalence of MetS varies directly with the DOI,  therefore, the prevalence of MetS was found in higher age group. In one study, the prevalence of MetS was found 37% in long-term schizophrenics, with a mean age of 45 years.  Also in this study, the mean age of patients having MetS was higher (36.92 years) as compared to the patients without MetS (34.75 years). The lower prevalence (28%) of MetS found in this study may partly due to younger age group.
In one study,  mean values of SBP, DBP, waist circumference, S. HDL, S. TG, and BMI were found significantly higher in patients having MetS as compared to patients without MetS. Our study also shows similar results. Waist circumference, fasting blood sugar, triglycerides, and BMI were found significantly higher in patients having MetS as compared to patients without MetS. Both SBP and DBP were found higher and HDL was lower in patients with MetS as compared to patients without MetS. However, the differences were not statistically significant.
Although the mean DOI was longer in patients with MetS as compared to the patients without MetS, the difference did not reach to the statistically significant level. The above-mentioned finding is similar to the conclusions of the study conducted by Ford et al.,  where the prevalence of MetS was higher in patients with longer DOI.
Thirty-eight patients (76%) were taking antipsychotics for more than 6 months of duration, in which 14 patients (28%) were found to have MetS. No patient has MetS who had taken antipsychotics for <6 months of duration. These findings are more or less similar to one group of investigators who found that people with schizophrenia (both those with first episodes and those chronically exposed to conventional medications) have more than three times as much intra-abdominal fat as controls matched for age, gender, and lifestyle and that 6 months of treatment with either olanzapine or risperidone, although increasing BMI does not significantly increase visceral fat stores. ,
Recent studies suggest that the syndrome is increased in people with schizophrenia and in particular in those taking the SGA drugs such as olanzapine and clozapine. , Our study also shows similar results. All the patients having MetS were taking SGAs (clozapine and olanzapine). This was statistically significant (P < 0.05). Statistically significant differences were not observed among the majority of socio-demographic parameters between patient and control group. Maximum numbers of subjects were in the age group of 21-30 years in all the groups and males were more than females in schizophrenia group. Statistically significant difference (P < 0.05) was found in domicile and education of the patient group. Control group was more significantly (P < 0.05) belongs to urban area when compared with the patient group. Subjects in control group were more educated as compared with patient group. The possible reason for this difference may be because of illness, the subjects of patient group were not able to study or have stopped their studies. There was no significant difference observed in religion, marital status, and socio-economic status of patient group and control group. The reason behind this may be because all the subjects of patient as well as control group belong to the same geographical area.
These patients have further increased the risk of MetS due to unhealthy lifestyle issues, e.g., poor diet, lack of exercise, and cigarette smoking, which are known to have higher prevalence in these patients than in the general population.
Findings of this study could not be corroborated because the studies on this category of patients are deficient in India.
| Conclusions|| |
The awareness of metabolic complications in schizophrenia should encourage clinicians and psychiatrists to screen first episode of psychosis for the predisposing factors of MetS. Once they have been prescribed medication, patients should be monitored on a regular basis. The blood tests and oral glucose tolerance, practical anthropometric measures of intra-abdominal fat such as waist circumference and waist-to-hip ratio should be taken. Psychiatrists should screen for such metabolic disturbances if patients have no access to primary care. Finally, simple lifestyle advice on the virtues of a balanced diet and regular exercise should be routinely given to all patients, as these are still the most effective ways of preventing diabetes and its related complications.
These values should be recorded and tracked for the duration of treatment. Clinicians should also encourage patients to monitor and chart their own weight. It is particularly important to monitor any alteration in weight following a medication change. The patients' psychiatric illness should not discourage clinicians from addressing the metabolic complications for which these patients are at increased risk.
| Limitations|| |
Due to the constraints of a time bound study and because of the stringent selection criteria, the sample size was small and hence the results are subjected to type II error and they cannot be generalized. The study is a cross-sectional study and to further assess the effect of psychotropic medication on MetS, longitudinal studies are needed.
| References|| |
|1.||Allebeck P. Schizophrenia: A life-shortening disease. Schizophr Bull 1989;15:81-9. |
|2.||Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: Findings from the third national health and nutrition examination survey. JAMA 2002;287:356-9. |
|3.||Chwastiak LA, Rosenheck RA, McEvoy JP, Keefe RS, Swartz MS, Lieberman JA. Interrelationships of psychiatric symptom severity, medical comorbidity, and functioning in schizophrenia. Psychiatr Serv 2006;57:1102-9. |
|4.||McIntyre RS, Konarski JZ. Tolerability profiles of atypical antipsychotics in the treatment of bipolar disorder. J Clin Psychiatry 2005;66:28-36. |
|5.||Marder SR, Essock SM, Miller AL, Buchanan RW, Casey DE, Davis JM, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004;161:1334-49. |
|6.||Mackin P, Bishop D, Watkinson H, Gallagher P, Ferrier IN. Metabolic disease and cardiovascular risk in people treated with antipsychotics in the community. Br J Psychiatry 2007;191:23-9. |
|7.||Mattoo SK, Singh SM. Prevalence of metabolic syndrome in psychiatric inpatients in a tertiary care centre in north India. Indian J Med Res 2010;131:46-52. |
|8.||Wander GS, Khurana SB, Gulati R, Sachar RK, Gupta RK, Khurana S, et al. Epidemiology of coronary heart disease in a rural Punjab population: Prevalence and correlation with various risk factors. Indian Heart J 1994;46:319-23. |
|9.||Zargar AH, Masoodi SR, Laway BA, Khan AK, Wani AI, Bashir MI, et al. Prevalence of obesity in adults: An epidemiological study from Kashmir Valley of Indian Subcontinent. J Assoc Physicians India 2000;48:1170-4. |
|10.||Thakore JH, Mann JN, Vlahos I, Martin A, Reznek R. Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. Int J Obes Relat Metab Disord 2002;26:137-41. |
|11.||De Hert M, van Eyck D, De Nayer A. Metabolic abnormalities associated with second generation antipsychotics: Fact or fiction? Development of guidelines for screening and monitoring. Int Clin Psychopharmacol 2006;21:S11-5. |
|12.||De Hert M, Hanssens L, van Winkel R, Van Eyck D, Wampers M, Scheen et al. Reversibility of antipsychotic treatment-related diabetes in patients with schizophrenia. Diabetes Care 2000;29:2329-30. |
|13.||D J Raina, DS Jamwal, Prevalance study of overweight/obesity and hypertension among rural adults IJCM 1997; 22:155-59. 17 |
|14.||Heiskanen T, Niskanen L, Lyytikäinen R, Saarinen PI, Hintikka J. Metabolic syndrome in patients with schizophrenia. J Clin Psychiatry 2003;64:575-9. |
|15.||Kato MM, Currier MB, Gomez CM, Hall L, Gonzalez-Blanco M. Prevalence of metabolic syndrome in hispanic and non-hispanic patients with schizophrenia. Prim Care Companion J Clin Psychiatry 2004;6:74-7. |
|16.||Ryan MC, Flanagan S, Kinsella U, Keeling F, Thakore JH. The effects of atypical antipsychotics on visceral fat distribution in first episode, drug-naive patients with schizophrenia. Life Sci 2004;74:1999-2008. |
|17.||American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes consensus statement. Diabetes Care 2004;27:596-601. |
|18.||Jin H, Meyer JM, Jeste DV. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: An analysis of 45 published cases. Ann Clin Psychiatry 2002;14:59-6 4. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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