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Keywords:

  • hypocholesterolemia;
  • obesity;
  • overweight;
  • schizophrenia;
  • underweight

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Aims

In Europe and North America, schizophrenia patients treated with antipsychotic agents have a higher prevalence of obesity and metabolic syndrome compared with healthy individuals. In Japan, the prevalence of overweight/obesity in the general population is considerably lower than that in Europe and North America. The purpose of this study was to investigate the prevalence of underweight and overweight/obesity as well as laboratory data in Japanese inpatients with schizophrenia.

Methods

The subjects were 333 inpatients with schizophrenia and 191 age- and sex-matched healthy volunteers. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2, standard weight was defined as BMI ≥ 18.5 to <25 kg/m2 and underweight was defined as BMI < 18.5 kg/m2.

Results

A significant difference in the prevalence of the three BMI levels was observed between schizophrenia patients and controls (P < 0.001). The prevalence of underweight was significantly higher in schizophrenia patients than that in controls (P < 0.001). The prevalence of hypoproteinemia (P < 0.001) and of hypocholesterolemia (P < 0.001) were significantly higher in schizophrenia patients than in controls. In schizophrenia patients, the prevalence of hypotriglyceridemia was significantly higher in the underweight group than in the standard weight group (P = 0.003) and in the overweight/obesity group (P < 0.001).

Conclusions

The prevalence of underweight in Japanese inpatients with schizophrenia may be higher compared with that in the general population. Therefore, the physical health of inpatients should be more carefully taken into account in clinical practice.

THE LIFE EXPECTANCY of schizophrenia patients is 15 years shorter than that of the general population. In schizophrenia patients, 50–75% of deaths are caused by ischemic heart disease.[1] Studies in Europe and North America have shown that schizophrenia patients treated with antipsychotic agents have a higher prevalence of obesity and metabolic syndrome (MetS) – risk factors for arteriosclerotic disease – compared with healthy individuals.[2, 3] In Japan, the prevalence of overweight/obesity in the general population is considerably lower than that in Europe and North America.[4] In Japan, it has been reported that the percentage of underweight schizophrenia inpatients is substantially higher compared with that in the general population.[5] A study on the relation between bodyweight and the risk of death in the general population showed that the risk of death due to overweight/obesity is lower in East Asia, including Japan, compared with that in Europe and North America, and an increased risk of death is prominent in the underweight group.[6, 7] Taking into account these ethnic differences, it is important to examine the prevalence of underweight and overweight/obesity in Japanese schizophrenia patients. Few large-scale studies, however, have examined these issues in Japan.

Another notable difference between Japan and other countries is that the mean duration of hospitalization for schizophrenia or delusional disorders is much longer in Japan than that in Europe and North America.[8] A total of 66.7% of all inpatients in psychiatric hospitals in Japan had been hospitalized for >1 year at the time of investigation, with schizophrenia or delusional disorder patients accounting for 59.1% of all inpatients.[8] Therefore, differences in health-care systems might affect the nutritional status of inpatients with schizophrenia.

The purpose of this study was to investigate the prevalence of underweight and overweight/obesity, as well as laboratory data, regarding nutritional status in Japanese inpatients with schizophrenia.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Participants

This study was conducted between January 2007 and December 2011. The subjects were 333 inpatients with schizophrenia aged 18–60 years (DSM-IV-TR) at nine psychiatric hospitals in Niigata Prefecture in Japan. One hundred and ninety-one age- and sex-matched healthy volunteers were also included as a control group. We excluded participants with the following conditions: overt physical illness; changes in drug therapy within the previous 4 weeks; or concurrent treatment with any drugs other than benzodiazepines and mood stabilizers. All subjects participated in this study after giving their written informed consent.

Procedure

Height and bodyweight were measured, and body mass index (BMI: weight in kilograms divided by the square of the height in meters) was calculated. To examine total protein (TP), total cholesterol (TC), triglyceride (TG), and fasting plasma glucose (FPG) levels, fasting blood samples were drawn after an overnight fast of ≥9 h. Plasma samples were centrifuged at 4°C and frozen at −80°C. Serum analysis was performed using the standard methods (SRL, Shinjuku-ku, Tokyo, Japan). Hypoproteinemia, hypoglycemia, hypocholesterolemia and hypotriglyceridemia were defined as TP < 6.7 g/dL, FPG < 70 mg/dL, TC < 150 mg/dL and TG < 50 mg/dL, respectively. Overweight/obesity was defined as BMI ≥ 25 kg/m2, standard weight was defined as BMI ≥ 18.5 to <25 kg/m2 and underweight was defined as BMI < 18.5 kg/m2. The study was approved by the Ethics Committee at Niigata University Graduate School of Medical and Dental Sciences. All data were treated anonymously, and private information was protected.

Statistical analysis

Clinical and demographic characteristics were compared between schizophrenia patients and controls or among categories of underweight, standard weight and overweight/obesity using the χ2 test, unpaired t-test, one-way analysis of variance and the Kruskal–Wallis test. The threshold for significance was set at P < 0.05. SPSS 19.0 (IBM Japan, Tokyo, Japan) was used for statistical calculations.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Table 1 compares BMI and nutritional status between schizophrenia patients and controls. A significant difference in the prevalence of the three BMI levels was observed between schizophrenia patients and controls. On post-hoc analysis, the prevalence of underweight was significantly higher in schizophrenia patients than that in controls (P < 0.001). TP (P < 0.001), FPG (P < 0.001) and TC (P < 0.001) were significantly lower in schizophrenia patients than in controls. The prevalence of hypoproteinemia (P < 0.001) and of hypocholesterolemia (P < 0.001) were significantly higher in schizophrenia patients than in controls (Table 1).

Table 1. BMI and nutrition status vs presence of schizophrenia
 Schizophrenia patientsControlsP
  1. Data given as %, mean ± SD or median (range). Unpaired t-test; χ2 test. Hypoproteinemia, TP < 6.7 g/dL; hypoglycemia, FPG < 70 mg/dL; hypocholesterolemia, TC < 150 mg/dL; hypotriglyceridemia, TG < 50 mg/dL. BMI, body mass index; BPRS, Brief Psychiatric Rating Scale; FPG, fasting plasma glucose; TC, total cholesterol; TG, triglycerides; TP, total protein.

Age (years)39.1 ± 11.937.5 ± 10.3n.s.
Male52.959.2n.s.
Smoker35.438.2n.s.
BPRS score30.5 ± 11.6 
Duration of hospitalization (months)2.9 (0.03–464.4) 
BMI (kg/m2)22.8 ± 4.122.9 ± 3.2n.s.
Underweight and overweight/obesity   
Overweight/obesity (BMI ≥ 25)26.722.0<0.001
Standard weight (BMI ≥ 18.5 to <25)59.273.8
Underweight (BMI < 18.5)14.14.2
TP (g/dL)7.0 ± 0.57.5 ± 0.4<0.001
Hypoproteinemia22.32.1<0.001
FPG (mg/dL)89.7 ± 9.194.4 ± 13.9<0.001
Hypoglycemia0.60n.s.
TC (mg/dL)181.5 ± 31.9201.8 ± 33.5<0.001
Hypocholesterolemia14.71.6<0.001
TG (mg/dL)105.5 ± 57.7118.9 ± 101.0n.s.
Hypotriglyceridemia7.513.60.031

Table 2 compares nutritional status between the BMI categories of underweight, standard weight and overweight/obese. The prevalence of smoking was significantly different between the three BMI levels (P = 0.007), as was the prevalence of hypotriglyceridemia (P < 0.001). On post-hoc analysis, in schizophrenia patients the prevalence of hypotriglyceridemia was significantly higher in the underweight group than in the standard weight group (P = 0.003) and the overweight/obesity group (P < 0.001).

Table 2. Demographic and nutrition status vs BMI in schizophrenia patients
 UnderweightStandard weightOverweight/obeseP
  1. Data given as %, mean ± SD or median (range). One-way ANOVA; χ2 test; §Kruskal–Wallis test. Overweight/obese, BMI ≥ 25 kg/m2; standard weight, BMI ≥ 18.5 to <25 kg/m2; underweight, BMI < 18.5 kg/m2. BMI, body mass index.

Age (years)40.5 ± 14.038.7 ± 11.938.2 ± 9.8n.s.
Male48.952.855.1n.s.
Smoker19.134.546.10.007
Duration of hospitalization (months)3.7 (0.23–424.8)2.8 (0.03–464.4)3.0 (0.1–407.0)n.s.§
Antipsychotics monotherapy76.679.269.7n.s.
Most used antipsychotics as monotherapy (%)Aripiprazole (33.3)Olanzapine (34.2)Olanzapine (30.6) 
Hypoproteinemia23.925.015.3n.s.
Hypoglycemia2.20.50.0n.s.
Hypocholesterolemia10.915.415.1n.s.
Hypotriglyceridemia21.76.42.3<0.001

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

We found that there was a higher prevalence of underweight in schizophrenia patients, while the prevalence of overweight/obesity in schizophrenia patients was not different from those in controls. Furthermore, higher prevalences of hypoproteinemia and hypocholesterolemia were observed in schizophrenia patients compared with controls (Table 1). In addition, in schizophrenia patients, a higher prevalence of hypotriglyceridemia was observed in underweight patients compared with standard weight and overweight/obese patients (Table 2). To the best of our knowledge, this is the first study to show that nutritional status in inpatients with schizophrenia is poorer than that of the general population using age–sex–BMI-matched healthy controls. Because hypocholesterolemia is associated with cerebral hemorrhage in the Japanese general population,[9] a high prevalence of hypocholesterolemia is a considerable problem for Japanese inpatients with schizophrenia. Kitabayashi et al. reported that the prevalences of obesity (BMI ≤ 25 kg/m2), normal weight, and underweight in 273 Japanese inpatients with schizophrenia was 30.8%, 53.1%, and 16.1%, respectively,[5] and this indicated that there is a high prevalence of underweight in Japanese inpatients with schizophrenia. The present results are consistent with the Kitabayashi et al. results.[5] The prevalence of underweight in the general population of Japan is only 8.1%,[10] while the percentage of underweight schizophrenia patients in the present study and in the Kitabayashi et al. study is clearly higher than that in the general population.[5] It is unknown whether problems of being underweight and undernourishment increase risk of death in schizophrenia patients in Japan. In the general population, however, the effect of being underweight on the risk of death has been reported.[6, 7] As a result of a pooled analysis on 19 cohort studies carried out with a total of 1.46 million non-Hispanic Caucasian subjects, the risk of death was found to increase more when a BMI of 25 was exceeded compared with a BMI of 22.5–24.9. Additionally, that pooled analysis found that the hazard ratio of the low-bodyweight group with BMI < 18.5 was 1.47 in men and 1.37 in women, with a significant increase in the risk of death.[6] Follow up was conducted on 1.10 million people for an average of 9.2 years in a similar pooled analysis carried out with Asian subjects, and it was found that the increased risk of death in the underweight group was prominent compared with that in European and US subjects. In East Asia, including Japan, the hazard ratio was found to be 1.23 for BMI 17.6–20.0, 1.72 for BMI 15.1–17.5, and 2.43 for BMI < 15, with a significant difference observed between the BMI levels.[7] With regard to being overweight/obese, a significant increase in the risk of death was observed for a BMI of 27.6 in East Asian subjects. The prevalence of obesity is lower in the Japanese general population than in Europe and the USA. Therefore, being underweight appears to be more strongly correlated with risk of death than obesity regarding the general population in Japan. These results suggest that the prevalence of underweight in schizophrenia inpatients is higher compared with that in the general public, and this may be increasing the risk of death in Japanese inpatients with schizophrenia.

It remains unknown, however, why there are many underweight schizophrenia inpatients. In this study, although it was not statistically significant, underweight had the longest duration of hospitalization (Table 2). This indicates that long hospitalization may have a bad influence on physical health in schizophrenia patients. Bone density is lower in schizophrenia patients undergoing antipsychotic drug treatment compared with that in the general public, and low bodyweight is related to low bone density.[11] Furthermore, inpatients often tend to have a lack of exercise and, according to a proposal by the World Health Organization, lack of exercise and smoking in addition to low bodyweight are factors causing a decline in bone density.[12] These may be the reasons for the high prevalence of underweight in schizophrenia inpatients who had the longest duration of hospitalization.

In the present study, there was no difference in the prevalence of overweight/obesity between schizophrenia patients and controls. The prevalence of overweight/obesity in the general population of Japan is 25.3%,[10] which is similar to the present results. In a cross-sectional study conducted in Japan, the prevalence of MetS was 15.8% in inpatients with schizophrenia and 14.1% in healthy volunteers,[13] with no difference found between groups. Health hazards due to being overweight/obese in inpatients with schizophrenia might not be different from the general population.

There were several limitations in this study. First, this study had a relatively small sample size, and therefore, may have been susceptible to yielding false-negative results. Second, the duration of hospitalization varied and many patients hospitalized for only a short time were included. The effect of the duration of hospitalization on BMI should be investigated in the future. Third, eating behaviors and the amount of exercise were not examined during hospitalization. Therefore, it is unknown what effects, if any, these factors may have on BMI.

Conclusions

The prevalence of underweight in Japanese inpatients with schizophrenia is higher compared with that in the general population. Therefore, it seems that the physical health of inpatients should be more carefully taken into account in clinical practice.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

We are grateful to the study participants. We thank Hiroshi Kusano and Nanako Yamazaki for excellent technical assistance. Dr Someya has received research support and honoraria from Asahi Kasei, Astellas Pharma, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, Takeda Pharmaceutical, and Yoshitomiyakuhin. Dr Suzuki has received research support and honoraria from Janssen Pharmaceutical, Otsuka Pharmaceutical and Mitsubishi Tanabe Pharma Corporation. The other authors have no conflicts of interest to disclose.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
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