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Keywords:

  • bipolar disorder;
  • calorimetry;
  • energy expenditure;
  • manic state

Abstract

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

Objective:  We aimed to assess the resting energy expenditure in bipolar I disorder, manic episode patients.

Method:  Forty-two bipolar I disorder, manic episode patients that were treated in the inpatient psychiatry clinic of Trakya University Hospital and had met the necessary study criteria were included along with 27 controls. DSM-IV criteria and the Bech-Rafaelsen Mania Rating Scale were used to evaluate patients’ diagnosis and severity of the manic episodes. The indirect calorimetry device was used to measure resting energy expenditure values.

Results:  Resting energy expenditure values of manic patients were found to be higher than those of the controls. Controls showed significant correlations between body mass index and resting energy expenditure, but manic patients did not exhibit similar correlations. There was also no relation between Bech-Rafaelsen Mania Rating Scale scores and resting energy expenditure values in manic patients.

Conclusions:  We found significantly increased resting energy expenditure values in bipolar I disorder, manic episode patients. These findings suggest a possible clinical use of resting energy expenditure for evaluation of bipolar I disorder manic episode and also suggest resting energy expenditure as a possible biological marker.

Bipolar disorder (BD) is a mood disorder that affects approximately 1% of the population (1, 2) and is characterized by extreme variations in mood, from mania and/or irritability to depression. Manic episodes are characterized by a predominantly elevated, expansive, or irritable mood, and manic patients classically have abundant resources of energy and engage in multiple activities and ventures (3).

Total energy expenditure (TEE) has three major components that when added together provide an accurate measurement of an individual’s daily caloric requirement. These include: (i) resting energy expenditure (REE), accounting for approximately 70% of TEE; (ii) energy expended in physical activity, accounting for approximately 20% of TEE; and (iii) the thermic effect of food (TEF), accounting for approximately 10% of TEE (4).

A manic episode is characterized by an inflated sense of self-importance, decreased need for sleep, extreme talkativeness, racing thoughts, and excessive participation in pleasure-seeking activities (5). Increased physical activity is correlated with increased energy expenditure in patients with manic episode. Physical activity has a profound effect on human energy expenditure and contributes to 20–30% to the body’s total energy output (6). Alternately, REE in a manic episode can be increased as REE represents the energy expended for normal cellular or organ function under post-absorptive resting conditions and defines the amount of calories required for a 24-hour period by the body during an inactive period.

One of the most valuable clinical tools used to measure REE is indirect calorimetry. Indirect calorimetry measures oxygen consumption and carbon dioxide production to calculate REE and respiratory quotient (7). It is referred to as ‘indirect’ because the caloric burn rate is calculated from a measurement of oxygen uptake. For optimal results, subjects are required to fast for 10–12 hours prior to a test, and to lie quietly during the duration of the test.

REE correlates closely with fat-free mass in lean and obese men and women. Although energy expenditure of metabolically active organs is responsible for a large component of REE, fat-free mass, which is composed primarily of skeletal muscle, accounts for most of the variability in energy expenditure between individuals (8). Researchers have reported that, for healthy adult humans, the relationship between REE and fat-free mass can be defined by a linear function model (9). Fat-free mass, fat mass, and age were also reported to be significant, independent predictors of REE in both men and women (10).

The aim of the present study was to assess the REE of bipolar I disorder (BD-I) manic episode patients and compare it with that of healthy controls.

Methods

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

Between June 2005 and June 2007, we conducted a prospective study on 135 hospitalized patients having the diagnosis of BD-I that were being treated in the Trakya University Hospital, Edirne, Turkey. From this group, 42 BD-I patients with single manic episode or most recent episode manic and 27 controls were examined. DSM-IV diagnoses for BD-I were verified by a staff psychiatrist (OC) and the Bech-Rafaelsen Mania Rating Scale (BRMAS) was also used to evaluate the patients’ diagnosis and severity of the manic episodes (11, 12). Since bipolar II disorder patients experience hypomanic episodes and this may have a possible impact on REE, they were not included in the study. Patients with concomitant medical diseases or patients using any medication for medical conditions other than BD were also not included in the study.

Thorough laboratory workup, including thyroid hormone levels, was provided to rule out metabolic and organic disorders. Informed consent was obtained from all the patients and their first-degree relatives. The control group consisted of volunteers recruited from among interns, hospital workers, resident doctors, and some patient relatives with no history of mental illness, or current medical conditions or medication use. Controls did not receive laboratory workups but were completely informed about the procedure and provided written consent. No payment or compensation was given to patients or controls.

REE of the manic patients was measured at the first reasonable opportunity following hospitalization. Due to the severity of the manic symptoms in some patients, the manic episode was stabilized prior to the REE measurement process, with all manic patients being measured during the first week of hospitalization. Measurements were made in the morning at 9:00 a.m. and food was withheld at 9:00 p.m. the prior evening. Subjects were awake, in the supine position, following eight hours of rest in an ambient environmental temperature that did not induce shivering or sweating.

REE was measured by breath-by-breath respiratory gas exchange with the VMax 29c (SensorMedics, Yorba Linda, CA, USA) indirect calorimetry device, using a mouthpiece and nose clip, following a 30-minute resting period. Gas analyzers were calibrated prior to each measurement against standard mixed reference gases. The mass flow sensor was also calibrated prior to each measurement. Measurements were carried out for at least 20 minutes. The steady state period was determined by the software and was defined as a five-minute period in which the average minute oxygen consumption (VO2) changed by less than 10% and the respiratory quotient (RQ) changed by less than 5%. REE was determined from VO2 and carbon dioxide production (VCO2) using the abbreviated Weir equation.

Statistical analysis was performed using the SPSS software package (version 10.0) and results were expressed as mean ± standard deviation. Student’s t-test was used to compare continuous variables and chi-square analyses for comparison of differences between the categorical variables. Pearson correlation analysis and regression analysis were used to determine the relationship between variables.

Results

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

The sex distribution, mean age, body mass index (BMI), REE, respiratory gas exchange measurements, and BRMAS of the groups are shown in Table 1. Because gender is a determining factor for REE, all the values are listed for both sexes. The mean ages of the groups were similar (= 0.13, p = 0.89). Sex distribution of the manic and control groups was also comparable (χ2 = 0.89, p = 0.34). One of the important factors that affect REE is body weight. Comparison of patients and controls in terms of BMI indicated no significant difference (= −0.71, p = 0.47).

Table 1.   Age, BMI, REE, respiratory gas exchange measurements, and BRMAS mean values of manic patients and controls
 Manic patientsControlsStatisticsa
MaleFemaleTotalMaleFemaleTotalMaleFemaleTotal
  1. Values are indicated as mean (SD).

  2. aChi-square test and Student’s t-test comparison of the groups and subgroups of male and females.

  3. BMI = body mass index (kg/m2); REE = resting energy expenditure (kcal/24 h); BRMAS = Bech-Rafaelsen Mania Rating Scale; VO2 = oxygen consumption; VCO2 = carbon dioxide production; VE = volume expired (minute ventilation).

n  22  20  42  11  16  27χ2 = 0.89, p = 0.34
Age36.45 (11.23)32.00 (9.51)34.33 (10.56)30.18 (8.48)36.63 (9.34)34.00 (9.41)= 1.63, p = 0.11t = −1.46, p = 0.15= 0.13, p = 0.89
BMI25.29 (4.00)25.36 (4.92)25.33 (4.40)24.06 (3.15)27.66 (6.60)26.19 (5.67)= 0.88, p = 0.38t = −1.19, p = 0.23t = −0.71, p = 0.47
REE1789.59 (499.92)1471.80 (352.15)1638.26 (459.65)1486.64 (471.44)1287.81 (454.17)1368.81 (463.02)= 1.67, p = 0.10= 1.37, p = 0.18= 2.37, p = 0.02
VO2 (ml/kg/min)3.27 (0.91)3.29 (0.97)3.28 (0.93)2.78 (0.66)2.57 (0.55)2.66 (0.59)= 1.57, p = 0.12= 2.64, p = 0.01= 3.39, p = 0.00
VO2 (l/min)0.25 (0.07)0.20 (0.05)0.23 (0.06)0.21 (0.07)0.18 (0.07)0.19 (0.07)= 1.53, p = 0.13= 1.18, p = 0.24= 2.15, p = 0.03
VCO2 (l/min)0.25 (0.08)0.19 (0.06)0.22 (0.07)0.19 (0.07)0.16 (0.06)0.17 (0.07)= 2.04, p = 0.05= 1.46, p = 0.15= 2.69, p = 0.01
VE (l/min)15.08 (3.89)13.79 (4.78)14.47 (4.33)11.59 (2.95)10.26 (3.04)10.80 (3.02)= 2.61, p = 0.01= 2.56, p = 0.01= 3.83, p = 0.00
BRMAS27.11 (4.54)28.84 (6.16)27.97 (5.41)

All of the patients were receiving medication, including lithium, antipsychotics, antiepileptics, or combinations of more than one, during the investigational period. The distribution of the medication groups was: 24 patients taking lithium, 17 chlorpromazine, 16 olanzapine, 13 valproic acid, 4 clonazepam, 4 quetiapine, 3 risperidone, one clozapine, one carbamazepine, one sulpiride, and one oxcarbazepine. No statistically significant difference between BRMAS scores of male and female patients was observed (= −0.98, p = 0.32).

Significant differences were observed in REE values between the manic group and controls (= 2.37, p = 0.02). Both male and female patients had higher REE values when compared with male and female controls independently. However, these differences did not reach significance (= 1.67, p = 0.10 and = 1.37, p = 0.18 for males and females, respectively).

There was a higher number of females in the control group. As females are known to exhibit lower REE than males, and as this fact carries a potential confounding impact on interpreting the results, we performed a further logistic regression analysis to exclude gender as a possible confound and observed that differences of REE values between manic and control groups remained (odds ratio = 1.02; 95 confidence interval: 1.01–1.03; p = 0.002).

No significant correlation between BMI and REE was found in the manic patient group. Subgroups of male manic and female manic patients also showed no statistically significant correlation between the same parameters. Alternately, significant correlations between BMI and REE were found in the full control group and subgroups of male and female controls (= 0.61, p = 0.001; = 0.75, p = 0.008; = 0.78, p = 0.000, respectively). There was no statistically significant correlation between BRMAS scores and REE values in either the full manic group or the subgroups of male and female patients.

Discussion

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

Mania is characterized by a period of intense activity and energy. Increased activity level is associated with increased energy need. The average physical activity level of healthy, well-nourished adults is a major determinant of their total energy requirement. Energy requirements are highly dependent on habitual physical activity. Physical activity level can be measured or estimated from the average 24-hour TEE and REE. Multiplying the physical activity level by the REE gives the actual energy requirement (13). In this context, increased levels of REE in manic patients were revealed in this study. REE levels in these patients could be interpreted as disproportionate to the TEE related to the physical activity levels of the patients, suggesting that REE may be a possible biological marker in BD-I manic episode.

The literature includes studies investigating energy expenditure changes in some psychiatric disorders. Nilsson et al. (14) reported patients with schizophrenia showing lower REE. Two studies using olanzapine therapy in psychosis suggest an increase in central body fat deposition and insulin and triglyceride levels but no effect on REE (15, 16). Though anorexia nervosa patients were shown to expend more energy by increasing their physical activity levels, basal metabolic rates were found to be lower than in those of the controls (17). Mochado-Vieira et al. (18) describe a case report of an acute manic episode associated with an energy drink.

Although patients with mania experience decreased sleep durations, absence of resultant fatigue is a typical feature (19, 20). Increased REE was reported in totally sleep-deprived rats (21), and the results indicate that sleep plays an important role in energy balance (22). According to our results, it can be inferred that increased REE of the patients may be partially related to sleep loss.

Gender, age, and body weight are the main determinants of TEE (23). In general, there exists a strong correlation between BMI and percentage of body fat. The positive relationship between energy expenditure and BMI has been previously reported in the literature (24). In our study this relationship was shown in control subjects, but BD-I manic episode patients showed no correlation between BMI and REE.

There are some limitations to this study: (i) all the patients included in the study were inpatients, meaning that more severe rather than mild or moderate cases were studied; (ii) patients could not always be evaluated for REE immediately after diagnosis was made, as some patients had to wait until they were stabilized with medication, which may have affected their energy expenditure; (iii) because the BMI measurements were similar between groups, no body composition assessments were conducted in the study.

As the increase in goal-directed activity or physical agitation is common in manic episode, increased REE may be related to the physical activity during the investigational period, and our results should also be interpreted with this in mind.

Since REE makes up the largest portion of human energy expenditure, any change in REE will have a significant impact on total energy. REE studies in manic patients can provide new opportunities for clinicians. With the accumulation of data from future studies, REE measurements may help psychiatrists to monitor their patients in remission and detect the development of mania earlier. Soreca et al. (25) have reported that patients with BD on long-term maintenance treatment may have reduced basal energy expenditure, which can result in weight gain. This finding, along with our results, suggests that REE could have an impact on the course of BD, assisting in the differential diagnosis of acute psychotic and manic episodes.

However, there are other medical and psychiatric conditions [e.g., cystic fibrosis (26), chronic obstructive pulmonary disease (27), and schizophrenia (28)] that may alter or increase REE and thus complicate its clinical use as a diagnostic tool. There are also some difficulties related to the implementation of indirect calorimetry on manic patients. The patients must remain stable during the investigation, and the requirement of 12 hours of fasting and delaying drug therapy until the end of the procedure are unwarranted complications. The accuracy of the test results depends on patient stability, test conditions, and lack of interruptions, all of which could be compromised in manic patients.

References

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