Participants
Between July 2008 and July 2009, 39 outpatients at the Department of Neuropsychiatry in the National Hospital Organization Takasaki General Medical Center who met the DSM-IV-TR criteria for major depressive disorder (MDD) [20] were asked to participate in this study. The purpose and procedures were explained by the patient’s psychiatrist. Exclusion criteria were comorbid conditions, including substance abuse, current medical conditions that might lead to global cognitive impairment or cerebrovascular risk factors, pregnancy that might cause alteration in adrenocortical activity, and specific medical contraindications for exercise.
Of the 39 who met the inclusion criteria, 18 agreed to participate.
Study protocol
The eighteen participants were invited to an exercise session at our hospital. After one month, they were also invited to a control session that involved sitting quietly. If the participant had been given antidepressants before entry, the dosage was fixed for the duration of the study.
At both sessions, we assessed the change in the saliva free cortisol level of each participant and the change in subjective depressive symptom scores before and after the sessions in order to examine the effect of the exercise on the participants’ depressive symptoms.
All participants provided written informed consent after a full explanation of the study purpose and procedures. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics council of the National Hospital Organization Takasaki General Medical Center.
Exercise session
The exercise that we chose was pedaling a bicycle ergometer (Aerobike 2000U, COMBI, Japan) by oneself.
Before participants’ routine consultation, they were invited to practice pedaling the bicycle ergometer for 15 minutes at the same time of day (between 13:00 and 14:00). The exercise load was unified with the Borg Rating of Perceived Exertion Scale (Borg RPE Scale), which is very popular in health sciences for quantifying exertion. It has been translated into many languages, including Japanese [21]. The scale values range from 6 (exertion: very, very light) to 20 (very, very hard), which denote heart rates ranging from 60-200 beats per minute. The participants were instructed to regulate their speed of pedaling the bicycle ergometer within the range from 11 (exertion: fairly light) to 13 (somewhat hard) on the Borg RPE Scale. In addition, the participant’s heart rate was recorded to show the actual exercise load that was done and the change in autonomic nerve system function related to the exercise.
To insure that the discomfort caused by the unfamiliar environment would not affect the participant’s saliva free cortisol level, the bicycle ergometer was set up in the room next to the consulting room, and their doctor was with the participant during the exercise session.
Control session
Within one month after the exercise session, the participants were asked to attend a control session. Of the 18 participants, three did not participate in the control session because they could not come to the hospital. Case 1 and 7 had reached complete remission and Case 8 had changed hospitals. As a result, the data of fifteen participants was available.
Also, before the routine consultation the participants were asked to sit quietly in a waiting room for 15 minutes. The control session took place at the same time of day (13:00-14:00) as the exercise session in order to exclude a change in the saliva free cortisol level based on the circadian rhythm.
Assessment and outcome measures
Severity of depressive symptoms
Before the exercise session, the level of depressive severity was assessed with the 17-item Hamilton Rating Scale for Depression (HRSD-17) [22]. This is a widely used semi-structured interview that covers a range of affective, behavioral, and physical symptoms of depression. The scores range from 0 to 52, with a score of 0-7 considered to be within the normal range or clinical remission, a score of 8-19 indicating mild severity, and a score of 20 or higher indicating at least moderate severity. An experienced psychiatrist, the attending doctor of the participant, administered the HRSD-17.
Health related quality of life
Before the exercise session, we examined psychosocial disability by measuring the health related quality of life (HRQOL) of each participant with the Medical Outcome Study Short-Form 36-Item Health Survey (SF-36) [23]. SF-36 is based on multi-dimensional health concepts and consists of the subscales of eight dimensions and the two summary scales shown below that measure the full range of health states. It has proved to be a useful HRQOL survey for many patient populations, including depressive patients [24–26]. We adopted version 2.0 of the SF-36 Japanese edition (SF-36v2™), which has been validated for the Japanese population [27–29]. SF-36v2™ uses norm-based scoring, so that we can calculate each score compared to the national-norm of 50. A higher score than 50 indicates better HRQOL than the national standard.
The eight SF-36 subscales and two summary scales are:
-
Physical functioning (PF): physical ability to do daily activities
-
Physical role functioning (RP): physical ability to fulfill a daily role, such as work or housework
-
Bodily pain (BP): perceived bodily pain
-
Social functioning (SF): ability to socialize with family and friends
-
General health (GH): subjective assessment of general health
-
Vitality (VT): perceived physical energy
-
Emotional role functioning (RE): ability to emotionally fulfill daily roles
-
Mental health (MH): feelings of depression and nervousness, or relaxation and fun. From the aggregation of these subscales, two distinct higher-level summary scores are available.
-
Physical component summary (PCS): general physical health state
-
Mental component summary (MCS): general mental health state
Participants’ preferences for physical exercise and their physical activity habits
Before the exercise session, the participants’ preferences for physical exercise, their daily exercise habits, and their reasons for exercising were asked via written inquiries and interviews. The questions were a) “Do you like exercise?” with answers “yes”, “no” or “uncertain”, b) “What kind of exercise do you actually do?” and c) “Why do you exercise?”.
Saliva free cortisol level
A saliva sample was collected from each participant three times during the exercise and control sessions: just before the session, immediately after the session, and 10 minutes later.
The reason for selecting 10 minutes after as the end point of saliva sampling is that it took 10 minutes for the heart rate at the end of the exercise period to return to the pre-exercise rate in our preliminary examination (Data not shown). At each saliva sampling, the participant was asked to bite a small cotton roll for 90 seconds, after which the cotton roll, including the participant’s saliva, was placed into a container (Salivette™, SARSTEDT AG & Co., Germany) designed to be able to remove the saliva from the cotton by centrifugation. During both sessions, the participant was instructed to refrain from gargling in order to prevent a change in the saliva free cortisol level.
The container was centrifuged at 1,000 g for 2 minutes and stored at -20°C until biochemical analysis. The saliva free cortisol level was measured by radioimmunoassay at the SRL Corporation (Tokyo, Japan) using a radioimmunoassay kit with 125I, (GammaCoat™ Cortisol, DiaSorin, Inc., Stillwater, MN). The saliva free cortisol level detection range of this kit is 0.06–9990 μg/dL.
Subjective depressive symptom score
To evaluate the change in subjective depressive symptoms before and immediately after the exercise and control sessions, eight depressive symptoms were self-rated.
Six of these symptoms, which we expected to be improved by a single session of exercise and that were easy for the participants to understand were excerpted from HRSD-17, a widely used semi-structured interview for the diagnosis of the severity of depression that has proven validity as a psychometric measure [22]. Moreover, it has been used as the outcome measure for assessing the effect of exercise in depressive patients [11–13]. The six symptoms we selected are depressed mood, disability of concentration (retardation is included in HRSD-17), agitation, anxiety, fatiguability (included in the somatic symptoms of HRSD-17), and hypochondriasis. In addition, we added two symptoms to the subjective depressive symptom score for this study. Perceived stress level and confidence about self-ability were not included in HRSD-17, but were expected to be improved by a single session of exercise.
Each symptom was scored on a four-point scale, ranging from 0 to 3. A score of 0 represents the absence of that subjective symptom, and the scores of 1, 2, and 3 indicate mild, moderate, or severe symptom respectively, except for confidence about self-ability. For this symptom, a higher score represents the lower confidence; the score was reversed when calculating the total subjective depressive symptom score.
Statistical analysis
All statistical analyses were performed using R version 2.9.0, a free software program for statistical computing [30]. The changes in the saliva free cortisol levels before, immediately after, and 10 minutes after the exercise and control sessions were evaluated with the Friedman-rank-sum-test. The changes in the subjective depressive symptom scores before and immediately after the sessions were evaluated with the Wilcoxon-signed-rank-test. These tests were adopted because the results of the Shapiro-Wilk test for saliva free cortisol level and the subjective depressive symptom scores before the exercise session suggested that these two variables were non-parametric.
The correlation between the changes in saliva free cortisol level and the changes in subjective depressive symptom scores before and immediately after the sessions were evaluated with the Spearman's-rank-correlation-coefficient. The correlation between the pre-exercise saliva free cortisol level and, HRSD-17 scores and SF-36v2™ scores were evaluated likewise.