The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 20, Number 11, 2014, pp. 823–830 ª Mary Ann Liebert, Inc. DOI: 10.1089/acm.2014.0205
Original Articles
Effects of Weekly One-Hour Hatha Yoga Therapy on Resilience and Stress Levels in Patients with Schizophrenia-Spectrum Disorders: An Eight-Week Randomized Controlled Trial Saeko Ikai, MD,1 Takefumi Suzuki, MD, PhD,1,2 Hiroyuki Uchida, MD, PhD,1,3 Juri Saruta, DDS, PhD,4,5 Keiichi Tsukinoki, DDS, PhD,4,5 Yasuo Fujii, MD, PhD,6 and Masaru Mimura, MD, PhD1
Abstract
Objective: To examine the effects of Hatha yoga therapy on resilience, brain-derived neurotrophic factor (BDNF) levels, and salivary alpha amylase (SAA) activity in patients with schizophrenia-spectrum disorders. Design and participants: Single-blinded, randomized controlled study in which outpatients with schizophrenia or related psychotic disorders (according to International Classification of Diseases, 10th Revision) were randomly assigned to a yoga or a control group. Setting: November 2012–April 2013 at Yamanashi Prefectural Kita Hospital, Japan. Interventions: In the yoga group, patients received weekly 1-hour Hatha yoga sessions, in addition to regular treatment, for 8 weeks. Those in the control group underwent regular treatment, which included a daycare rehabilitation program. Outcome measures: Assessments included the 25-item Resilience Scale (RS), Positive and Negative Syndrome Scale (PANSS), plasma and salivary BDNF level, and SAA activity. Results: Fifty patients participated (25 in each group; mean age – standard deviation, 50.9 – 11.3 years; mean duration of illness, 25.0 – 10.3 years; mean total PANSS score, 78.2 – 17.3). No significant differences in changes in any variable from baseline to week 8 were found between the two groups (changes in the yoga group versus the control group: RS score, - 1.6 – 19.9 versus 0.3 – 17.2; PANSS score, 0.5 – 12.0 versus 5.0 – 15.6; plasma BDNF, 41.6 – 377.0 pg/dl versus 73.4 – 346.0 pg/dl; SAA, - 26.2 – 72.6 kU/l versus - 13.8 – 68.0 kU/l, respectively). Conclusions: Adjunct yoga therapy showed no positive changes in resilience level or stress markers. Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy. oga has been practiced for several millennia1 and includes a variety of movements and poses that are performed in coordination with breath control, meditation, relaxation, and lifestyle. As such, yoga is expected to improve not only physical conditions but also mental wellness.2 For example, recent evidence obtained from randomized controlled trials indicated benefits of yoga therapy for patients with schizophrenia; psychiatric symptoms improved with this intervention in addition to ongoing antipsychotic
Y
treatment,3–6 although the data in this field still remain scarce and inconclusive.7 Moreover, yoga has reduced stress levels,8–10 which is especially relevant for patients with schizophrenia given the close relationship between stress and relapse in this patient population.11 ‘‘Resilience’’ is defined as a positive adaptation and maintenance of competent function even in the face of prolonged stress and adversities.12,13 Some individuals, despite marked negative circumstances and risk factors,
1
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Department of Psychiatry, Inokashira Hospital, Tokyo, Japan. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 4 Department of Oral Sciences, Kanagawa Dental University Graduate School of Dentistry, Kanagawa, Japan. 5 Research Institute of Salivary Gland and Health Medicine, Kanagawa Dental University Graduate School of Dentistry, Kanagawa, Japan. 6 Department of Neuropsychiatry, Yamanashi Prefectural Kita Hospital, Yamanashi, Japan. 2 3
823
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
824
remain healthy or easily recover from adverse events, while others under similar conditions seem vulnerable to disorders.14 Pathoetiology of schizophrenia has conventionally been investigated to seek new treatment approaches that will normalize the aberrant conditions. However, while such a traditional approach is valid, it is also critically important to focus on patients’ resilience in order to understand mechanisms of recovery of this illness. In fact, good resilience increases the chance of long-term recovery in patients with schizophrenia.15 Thus, the concept of resilience has recently gained wide attention. Because practicing yoga could reduce stress levels, it would be beneficial to test the idea that such therapy may have some beneficial effects on resilience levels in patients with schizophrenia. No existing studies appear to have studied this topic. Stress suppresses neurogenesis through a process that involves brain-derived neurotrophic factor (BDNF).16 Salivary alpha amylase activity (SAA) levels increasingly can be used as an accessible measure of sympathetic nervous system reactivity to stressors.17 However, no data are available on yoga’s effects on those measurable biological stress markers. On the basis of this background, the current 8-week, single-site, single-blind, randomized controlled trial evaluated the effects of adjunctive weekly Hatha yoga therapy on resilience level, BDNF, and SAA activity in outpatients with schizophrenia-spectrum disorders. Materials and Methods Study design
In this study, eight weekly sessions of Hatha yoga therapy were added to ongoing regular psychopharmacologic treatment, together with a follow-up visit after an additional 8 weeks. This study was conducted in Yamanashi Prefectural Kita Hospital, Yamanashi, Japan, between November 2012 and April 2013. The hospital’s institutional ethics board approved the study, and all participants provided written informed consent after being given a full description of the study. The study was registered at the University Medical Information Network Clinical Trial Registry (Identifier: UMIN000009305). Participants
Outpatients who were diagnosed with schizophrenia or related psychotic disorders (F20–F25 according to the International Classification of Diseases, 10th edition),18 were age 18 years or older, had been receiving the same medications for the 8 weeks preceding entry, and were registered in the daycare center in the hospital were approached and asked to participate in this study. Patients who were incapable of providing consent or suffered from active alcohol abuse or other psychiatric comorbidities were excluded; to ensure representativeness of the sample, no other exclusion criteria were applied. Medications were kept constant by the patients’ treating psychiatrists throughout the study period unless a change was clinically indicated. Intervention
The patients were randomly assigned to either a yoga therapy group or treated-as-usual group. The randomization was performed by using sealed envelopes prepared by physicians at Yamanashi Prefectural Kita Hospital who were not involved in
IKAI ET AL.
this study. An envelope method was used to randomly divide the patients into two groups. A simple randomization list with no special stratification or blocks was made by using a computer program. One of the four physicians opened the envelopes after the baseline assessment. Patients assigned to the yoga group received a weekly 1-hour session of Hatha yoga therapy between 9:40 and 10:40 a.m. on Mondays in the hospital gymnasium for a total of eight sessions. Participants were asked not to perform selfpractice of yoga therapy at home. The sessions were provided as an adjunct to regular ambulatory treatment by one of the authors, who was an instructor with a master’s degree in Hatha yoga. Each session consisted of gentle yoga stretches and simple movements in coordination with breathing (gentle movements of major muscle groups), asana (twisting poses and standing poses), deep relaxation, and breathing exercises.19 After the completion of the 8-week intervention, patients received treatment as usual but did not receive any yoga therapy until the follow-up assessment was performed. Patients in the control group attended a weekly regular daycare program (which provided social skills and walking) for 8 weeks. After the completion of the 8-week observation period, the patients in this group were allowed to attend Hatha yoga sessions upon request, which was offered outside the present trial. Outcome measures
The primary outcome measure was resilience level at week 8 assessed with the 25-item Resilience Scale.20 This scale measures the degree of individual resilience and is considered to represent a positive personality characteristic that enhances individual adaptation. The scale covers five factors of resilience: purpose, perseverance, self-reliance, equanimity, and existential aloneness. Items are scored on a 7-point scale ranging from 1 = disagree to 7 = agree, with possible scores ranging from 25 to 175; a higher score indicates greater individual resilience. The secondary outcome measures included fasting blood glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, plasma and salivary BDNF, and SAA. These measurements took place between 9:00 a.m. and 12:00 p.m. at baseline and week 8 in both groups. The following assessments were also performed: the Positive and Negative Syndrome Scale (PANSS),21 the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS),22 the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz),23 and the EuroQol-5 dimensions (EQ-5D) classification system.24 Follow-up assessments at week 16 in the yoga group included the RS, fasting blood glucose, total cholesterol chol, HDL cholesterol, LDL cholesterol, triglycerides, BDNF, SAA, and the EQ-5D. All assessments were performed by trained psychiatrists who were blind to the patients’ allocations and were not involved in the yoga therapy. Information collected included sex, age, duration of illness, body–mass index, physical comorbidities, waist circumference, and psychotropic medications. Daily doses of antipsychotics, including depot antipsychotics, were converted to chlorpromazine equivalents.25,26 Venous blood samples were centrifuged at 3000 rpm for 10 minutes. All plasma samples were then stored at - 30
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
YOGA AND RESILIENCE IN SCHIZOPHRENIA
825
until analyzed. Plasma and salivary concentrations of BDNF were measured according to the procedure supplied by the manufacturer (CYT306; Millipore Corp., Bedford, MA). To quantify SAA, a salivary alpha-amylase monitor (NIPRO, Osaka, Japan) was used. This biosensor is composed of a disposable test strip and a hand-held reader. The precision (coefficient of variation) was reported as 8.1%, and its repeatability has measurement reliability.27 The saliva sample was collected by dipping a sampling strip under the tongue for 30 seconds. The level of SAA was used as a proxy of acute stress.17
interest between the yoga and control groups. In addition, repeated-measures analysis of variance was used to compare the variables between baseline and weeks 8 and 16 in the yoga group. When appropriate, post hoc analyses were performed with Bonferroni correction. The Pearson test was used to examine correlations in the changes of the variables. Main analyses were performed by using a last-observationcarried-forward method. Completer analysis was also used. All tests were two tailed, and p < 0.05 was considered to represent a statistically significant difference. Results
Statistical analyses
No formal sample size calculation was performed because there has been no study on which to base sample size estimation. Statistical analyses were carried out using SPSS software, version 20 (IBM Corp., Armonk, NY). Patients’ baseline characteristics were compared between the two groups by using the chi-square test or the independent t-test. The Mann-Whitney U test was used for age, duration of illness, body–mass index, dose of antipsychotics, FACT-Sz score, DIEPSS score, EQ-5D (index), SAA, triglycerides, HDL cholesterol, fasting blood glucose, and plasma and salivary BDNF because these were not distributed normally (according to the Shapiro-Wilk test of normality). Analysis of covariance (ANCOVA) with baseline values as covariates was used to compare changes at week 8 in the variables of
Patient characteristics
Eighty-one outpatients with schizophrenia-spectrum disorders registered in the daycare center were approached for possible participation in this study. Nineteen outpatients declined to participate because of their schedules and 12 had little interest in yoga therapy. Thus, 50 outpatients agreed to participate in this study and were allocated to either the yoga therapy group (n = 25) or the control group (n = 25). Characteristics and disposition of participants are shown in Table 1 and Figure 1, respectively; there were no significant differences at baseline between those two groups. All participants were Japanese. Forty-one patients had schizophrenia and 9 had schizoaffective disorder. Physical comorbidities were as follows: hyperlipidemia (14%; n = 7),
Table 1. Demographic and Clinical Characteristics of Patients Characteristic Age (y) Men, n (%) Duration of illness (y) Body–mass index (kg/m2) Dose of antipsychotics (CPZE mg/d) Waist circumference (cm) PANSS Total score Positive symptom score Negative symptom score General psychopathology score FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score Resilience Scale score SAA (kU/L) Total cholesterol (mg/dL) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL)
Yoga group (n = 25)
Control group (n = 25)
53.5 – 9.9 16 (64.0) 25.3 – 9.6 24.6 – 6.2 659.3 – 386.2 92.3 – 10.7
48.2 – 12.3 17 (68.0) 24.7 – 11.1 24.5 – 3.1 733.5 – 432.5 90.6 – 11.8
NA NA NA NA NA 0.52
0.14 0.77 0.76 0.78 0.71 0.42
76.3 – 18.5 15.6 – 5.1 21.1 – 5.3 39.6 – 12.1 56.7 – 11.8 1.5 – 1.9 0.86 – 0.24 71.3 – 18.7 114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.0
80.2 – 16.1 16.9 – 5.1 21.1 – 4.4 41.7 – 8.5 56.8 – 6.2 2.2 – 2.9 0.80 – 0.23 68.8 – 17.2 109.2 – 30.4 123.9 – 127.7 198.0 – 33.5 159.7 – 74.3 120.7 – 29.4 49.6 – 16.5 123.2 – 34.7 274.1 – 471.0 412.1 – 825.6
- 0.78 - 0.84 0.02 0.16 NA NA NA 0.50 0.61 NA 0.34 NA - 0.81 NA NA NA NA
0.44 0.41 0.98 0.68 0.43 0.46 0.64 0.50 0.91 0.99 0.63 0.69 0.70 0.26 0.61 0.90 0.91
t
p-Value
Unless otherwise noted values are expressed as the mean – standard deviation. Group differences were compared by using chi-square test, independent t-test, or the Mann-Whitney test (see text for details). BDNF, brain-derived neurotrophic factor; CPZE, chlorpromazine equivalent; DIEPSS, Drug Induced Extrapyramidal Symptoms Scale; EQ-5D, EuroQol 5 dimensions; FACT-Sz, Functional Assessment for Comprehensive Treatment of Schizophrenia; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NA, not applicable; PANSS, Positive and Negative Syndrome Scale; SAA, salivary alphaamylase activity; TG, triglyceride; VAS, visual analogue scale.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
826
IKAI ET AL.
FIG. 1. Flow of patients through the study.
hypertension (12%; n = 6), diabetes mellitus (2%; n = 1), hyperuricemia (2%; n = 2), and arrhythmia (2%; n = 2). Antipsychotic medications at baseline were olanzapine (32%; n = 16), risperidone (20%; n = 10), fluphenazine (14%; n = 7), aripiprazole (10%; n = 5), clozapine (8%; n = 4), levomepromazine (4%; n = 2), paliperidone (4%; n = 2), bromperidol (2%; n = 2), chlorpromazine (2%; n = 2), haloperidol (2%; n = 2), and sulpiride (2%; n = 2). Twenty patients (40.0%) were receiving two or more antipsychotics. Medication adherence was acceptable judging from patients’ interview for both groups. Only one participant (in the control group) experienced a change in the medication regimen from paliperidone, 3 mg/d, to risperidone, 4 mg/d, because of worsening delusions. Treatment outcomes
Seven participants (28.0%) in each group prematurely withdrew from the study. The reasons of withdrawal were refusal to continue (6 participants in the yoga group and 5 participants in the control group), relapse (1 participant in the control group), and difficulty matching the schedule (1 each in the yoga and control groups). No significant differences were observed in changes from baseline to week 8 in any of the variables of interest in both groups (Table 2). The ANCOVA with baseline values as covariates also showed no significant differences in changes in any of the variables of interest between the groups (Table 3). Additionally, no clinical gains were observed with this intervention, as indicated in Table 4. In the yoga group, there was a modest correlation between the changes from the baseline to week 8 in the SAA activity and the RS (c = 0.403; p = 0.046), but they were not significantly correlated in the control group (c = 0.203; p = 0.158). As for the follow-up assessment at week 16 in the yoga group, only SAA significantly decreased compared with the baseline according to repeated-measures analysis of
variance (Table 4); however, this difference was no longer seen after Bonferroni correction. Completer analysis
Results of completer analysis are shown in the Supplementary Tables S1–S4 (Supplementary Data are available online at www.liebertpub.com/acm). Briefly, significant group differences were observed only in total PANSS score (mean – standard deviation: yoga group, 73.5 – 18.0 to 73.5 – 15.2; control group, 81.4 – 17.7 to 88.7 – 20.6) and general psychopathology score (yoga group, 38.1 – 13.0 to 36.9 – 8.0; control group, 42.3 – 9.5 to 46.6 – 14.3) with ANCOVA. At the follow-up assessment at week 16 in the yoga group, only SAA showed a significant decrease, which is consistent with the results of the last-observation-carried-forward method. Discussion Main findings
To the authors’ knowledge, this is the first study to assess the effect of Hatha yoga therapy on resilience, plasma and salivary BDNF, and SAA activity in patients with schizophrenia-spectrum disorders. Contrary to expectation, no variables significantly improved after the 8-week yoga intervention. However, these negative findings provide insights into improving the format and design of future yoga therapies, including frequency and duration, to achieve clinical gains in patients with schizophrenia discussed below. Such improvements might be beneficial given the past positive evidence of yoga therapy in improving physical and psychological conditions in other populations.3–6,28 Yoga therapy and resilience
Past evidence on yoga and resilience in healthy people and psychiatric patients is scarce and preliminary. Khalsa
YOGA AND RESILIENCE IN SCHIZOPHRENIA
827
Table 2. Analysis of Covariance for Resilience, Biological Markers, Psychopathology, Extrapyramidal Symptoms, and Quality of Life Yoga group (n = 25)
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dl) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) PANSS Total score Positive symptom Negative symptoms General psychopathology FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score
Control group (n = 25)
Baseline
Week 8
Baseline
Week 8
114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.0
112.7 – 22.6 109.2 – 111.6 199.8 – 32.4 162.8 – 137.2 117.1 – 31.8 54.8 – 17.4 122.0 – 34.4 190.7 – 598.8 208.3 – 342.5
109.2 – 30.4 123.9 – 127.7 198.0 – 33.5 159.7 – 74.3 120.7 – 29.4 49.6 – 16.5 123.2 – 34.7 274.1 – 471.0 412.1 – 825.6
109.5 – 29.2 110.1 – 133.1 199.7 – 35.6 160.1 – 73.2 119.8 – 27.8 49.7 – 13.8 119.6 – 24.4 347.6 – 652.2 383.3 – 561.2
76.3 – 18.5 15.6 – 5.1 21.1 – 5.3 39.6 – 12.1 56.7 – 11.8 1.5 – 1.9 0.86 – 0.24 71.3 – 18.7
76.8 – 16.2 16.0 – 4.6 21.8 – 5.7 39.0 – 16.2 55.8 – 10.4 1.4 – 1.8 0.82 – 0.25 72.8 – 17.1
80.2 – 16.1 16.9 – 5.1 21.1 – 4.4 41.7 – 8.5 56.8 – 6.2 2.2 – 2.9 0.80 – 0.23 68.8 – 17.2
81.8 – 25.5 18.0 – 4.9 22.5 – 5.0 44.7 – 13.3 56.3 – 8.1 2.9 – 2.8 0.67 – 0.31 64.8 – 20.4
F-Value
p-Value
0.004 0.289 0.127 1.420 1.297 0.047 0.996 0.053 0.569
0.948 0.594 0.723 0.240 0.262 0.829 0.324 0.819 0.455
2.256 1.028 0.516 2.558 - 0.348 3.570 3.009 2.172
0.140 0.316 0.476 0.117 0.730 0.065 0.089 0.147
Unless otherwise noted, values are expressed as the mean – standard deviation.
and colleagues reported that the resilience level, measured with the RS, slightly improved with yoga while most outcome measures, inclusive of the RS, exhibited a pattern of worsening in the control group over time among adolescents in secondary school.29 Preventive benefits in psychosocial well-being were also reported when Kripalu yoga (which consists of three stages: willful practice, surrender, and
meditation in motion) was practiced among students in 11th and 12th grades, although the RS scores did not significantly change.30 On the other hand, women with mental distress significantly improved on measures of stress and psychological outcome after a 3-month yoga intervention.31 Further, yoga therapy decreased SAA activity in both elderly and young people,32 in whom a decrease in SAA is
Table 3. Changes in Resilience, Biological Markers, Psychopathology, Extrapyramidal Symptoms, and Quality of Life in Yoga and Control Groups from Baseline to Week Eight Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dl) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) PANSS Total score Positive symptom Negative symptoms General psychopathology FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score
Yoga group (n = 25)
Control group (n = 25)
p-Value
- 1.6 – 19.9 - 26.2 – 72.6 - 1.7 – 33.2 - 41.7 – 178.5 3.9 – 15.0 - 0.1 – 5.7 7.5 – 26.7 41.6 – 377.0 - 7.8 – 108.3
0.3 – 17.2 - 13.8 – 68.0 1.9 – 13.6 0.7 – 56.5 - 2.1 – 14.5 0.1 – 5.7 - 3.6 – 28.9 73.4 – 346.0 - 28.1 – 611.7
0.83 0.35 0.44 0.47 0.19 0.97 0.63 0.23 0.41
0.5 – 12.0 0.4 – 2.0 0.7 – 2.7 - 0.6 – 9.1 - 0.9 – 4.0 - 0.1 – 1.4 - 0.03 – 0.15 1.5 – 16.4
5.0 – 15.6 0.8 – 3.8 1.4 – 4.4 2.7 – 11.3 - 0.4 – 5.7 0.6 – 1.5 - 0.11 – 0.26 - 4.0 – 17.3
0.43 0.82 0.51 0.58 0.29 0.66 0.33 0.63
Unless otherwise noted, values are expressed as the mean – standard deviation. Group differences were compared by using the MannWhitney test.
828
IKAI ET AL.
Table 4. Repeated-Measures Analysis of Variance in Yoga Group (n = 25)
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dL) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) EQ-5D index EQ-5D VAS score
Baseline
Week 8
Week 16
F-Value
p-Value
114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.6 0.86 – 0.24 71.3 – 18.7
112.7 – 22.6 109.2 – 111.6 199.8 – 32.4 162.8 – 137.2 117.1 – 31.8 54.8 – 17.4 122.0 – 34.4 190.7 – 598.8 208.3 – 342.5 0.83 – 0.25 72.8 – 17.1
118.0 – 28.0 96.2 – 86.7 200.6 – 35.7 163.5 – 146.6 117.8 – 31.9 56.9 – 17.1 121.6 – 24.7 69.4 – 83.9 179.3 – 324.7 0.86 – 0.24 71.3 – 20.6
1.420 3.541 0.043 1.214 1.051 1.642 1.044 1.169 1.563 0.929 0.193
0.252 0.037a 0.958 0.306 0.359 0.205 0.360 0.319 0.220 0.402 0.825
Unless otherwise noted, values are expressed as the mean – standard deviation. a Significant difference ( p < 0.05).
considered to represent an attenuated sympathetic tone. Relevant here is a finding that the SAA level was higher in patients with schizophrenia than in healthy people.33 In the present study, the RS scores did not change in either group. The lack of significant changes may be attributable to characteristics of the sample, including their relatively older mean age compared with previous studies. Moreover, the mean duration of illness was as long as approximately 25 years, which represents the chronicity of the illness in the participants and may limit any room for improvements in resilience levels in the present study. SAA activity as an index of acute stress also did not change. However, this study assessed outpatients in the chronic stage of the illness, and any extrapolation of our findings to other patient populations, such as younger patients with acute disease or older patients, should be done with caution. Additionally, we did not evaluate more exhaustive parameters of stress and autonomic functioning, including hypothalamic-pituitary-adrenal axis hormones, heart rate variability, positional blood pressure, and baroreceptor sensitivity. Yoga therapy and BDNF
BDNF is a trophic factor involved in the development of the brain and may influence neuroplasticity in schizophrenia.34 Stress and depression suppress neurogenesis through a process that probably involves this substance.16 Interventions that reportedly increase the BDNF level, such as exercise and antidepressant treatment, may help preserve brain function. In this context, practice of Sudarshan Kriya yoga increased serum levels of BDNF.35 In a study on the effect of yoga on BDNF levels among depressed patients in India, Naveen et al.36 observed that the change in BDNF did not significantly differ across three groups (i.e., yoga only, yoga and antidepressants, and antidepressants only). However, no studies have addressed this topic in patients with schizophrenia to date. In the current study, levels of both plasma and salivary BDNF did not significantly change. The study did not control for dose or type of antipsychotics. In a review, Favalli et al. suggested that typical antipsychotics decrease serum BDNF levels while atypical counterparts maintain or increase the levels.37 As such, use of various antipsychotics may have affected the current results. Additionally, a recent
meta-regression showed the evidence of lowered levels of brain BDNF in patients with schizophrenia as they grow older;34 the current participants were experiencing a relatively chronic course of their illness, with a mean illness duration of 25.0 – 10.3 years. Recommendations for future studies
Several points should be considered in planning future studies. The first concerns duration and intensity of the yoga therapy. In a previous study, the authors focused on the effects of yoga on postural sway in patients with chronic schizophrenia.19 Although the yoga intervention (i.e., a weekly 1-hour yoga session for 8 weeks) improved postural instability, it was insufficient to improve resilience and stress levels in this study. To further optimize yoga therapy, longer duration or greater intensity may be necessary in future trials. Second, intensity of yoga sessions should be considered; a once-a-week session may be insufficient. Third, the content of the yoga therapy may need to be adjusted for an elderly population to accommodate their physical strength and range of joint motion. Fourth, the data from multisite studies of yoga therapy in psychiatric patients are very scarce. Further yoga studies should deal with many participants from multiple institutions with diverse cultural/ethnic backgrounds. Finally, it is impossible to conduct double-blind studies with yoga, thereby necessitating more mechanistic research.2 Limitations
Apart from the issues already discussed above, several other limitations should be noted. First, this study was limited by its small sample size (n = 50) and lack of formal sample size calculation. This may have limited the statistical power to detect any possible differentials in resilience, BDNF, and SAA between the groups and thus makes the work preliminary. Second, the results should be interpreted in the context of type, duration, and intensity of the Hatha yoga intervention in this study. The yoga sequence involved different types of posture in this study. The effect of yoga therapy on psychological or pathological scales might be due to the modified yoga therapy used by one author. Finally, most participants in this study had long been taking various antipsychotics
YOGA AND RESILIENCE IN SCHIZOPHRENIA
that potentially affect metabolic markers in a negative manner, which would make it difficult to capture any positive changes in a short study.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Conclusions
This appears to be the first study to focus on the effect of Hatha yoga therapy on resilience, BDNF, and SAA activity in patients with schizophrenia. The results were negative. However, these results alone should not discourage further critical appraisal of this intervention because of its theoretical benefits and past positive evidence in a variety of settings and populations. In light of the paucity of the available data, these results emphasize the need for further investigations on the potential benefits of yoga therapy in patients with schizophrenia. Acknowledgments
We gratefully acknowledge the assistance of the regular day-care program staff in Yamanashi Prefectural Kita Hospital. The authors thank Drs. Ryoji Miyata, Akiko Kano, Fuminari Misawa, Mihoko Kobayashi, Hirokazu Shida, Waka Nogami, Hideaki Tani, Nobuhiro Nagai, Tatsuichiro Takahashi, Maho Hasebe, Toru Yamashita, Minako Sato, Hisashi Kida, Ryosuke Tarumi, Gentaro Miura, Saiko Ema, and Hodaka Yaegashi; Ms. Ai Otani; Ms. Aki Tozawa; and Ms. Atsuko Ikubo for their continuous support. Author Disclosure Statement
Dr. Ikai has received manuscript fees or speaker’s honoraria from Dainippon Sumitomo, Novartis, and Janssen Pharmaceutical within the past 3 years. Dr. Suzuki has received manuscript or speaker’s fees from Astellas, Dainippon Sumitomo, Eli Lilly, Elsevier Japan, Janssen, Meiji Seika, Novartis, Otsuka, and Weily Japan. Dr. Uchida has received grants from Astellas Pharmaceutical, Eisai, Otsuka Pharmaceutical, GlaxoSmithKline, Shionogi, DainipponSumitomo Pharma, Eli Lilly, Mochida Pharmaceutical, Meiji-Seika Pharma, Janssen Pharmaceutical, and Yoshitomi Yakuhin and speaker’s honoraria from Otsuka Pharmaceutical, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Dainippon-Sumitomo Pharma, Meiji-Seika Pharma, Abbvie, and Janssen Pharmaceutical within the past 3 years. Dr. Fujii has received speaking fees from Janssen Pharmaceutical and Eli Lilly within the past 3 years. Dr. Mimura has received grants and/or speaker’s honoraria from Asahi Kasei Pharma, Astellas Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji-Seika Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi Pharma, and Yoshitomi Yakuhin within the past 3 years. References
1. Iyengar B. Light on Yoga. New York: Schocken Books, 1996. 2. Balasubramaniam M, Telles S, Doraiswamy PM. Yoga on our minds: a systematic review of yoga for neuropsychiatric disorders. Front Psychiatry 2012;3:117.
829
3. Behere RV, Arasappa R, Jagannathan A, et al. Effect of yoga therapy on facial emotion recognition deficits, symptoms and functioning in patients with schizophrenia. Acta Psychiatr Scand 2011;123:147–153. 4. Duraiswamy G, Thirthalli J, Nagendra HR, Gangadhar BN. Yoga therapy as an add-on treatment in the management of patients with schizophrenia—a randomized controlled trial. Acta Psychiatr Scand 2007;116:226–232. 5. Visceglia E, Lewis S. Yoga therapy as an adjunctive treatment for schizophrenia: a randomized, controlled pilot study. J Altern Complement Med 2011;17:601–607. 6. Xie J, Lin Y, Guo C, Chen F. Study of influences of yoga on quality of life of schizophrenic inpatients. J Nursing (China). 2006;13:9–11. 7. Cramer H, Lauche R, Klose P, et al. Yoga for schizophrenia: a systematic review and meta-analysis. BMC Psychiatry. 2013;13:32. 8. Brown RP, Gerbarg PL. Yoga breathing, meditation, and longevity. Ann N Y Acad Sci. 2009;1172:54–62. 9. Chong CS, Tsunaka M, Tsang HW, et al. Effects of yoga on stress management in healthy adults: a systematic review. Altern Ther Health Med 2011;17:32–38. 10. Li AW, Goldsmith CA. The effects of yoga on anxiety and stress. Altern Med Rev 2012;17:21–35. 11. Howes OD, McDonald C, Cannon M, et al. Pathways to schizophrenia: the impact of environmental factors. Int J Neuropsychopharmacol 2004;7 Suppl 1:S7–S13. 12. Lutha SS, Cicchetti D. The construct of resilience: implications for interventions and social policies. Dev Psychopathol 2000;12:857–885. 13. Yagi K. [Resilience in mental disorders—special reference to biological research.] Seishin Shinkeigaku Zasshi 2008; 110:770–775. 14. Schumacher J, Leppert K, Gunzelmann T, et al. The resilience scale—a questionnaire to assess resilience as a personality characteristic. Z Klin Psychol Psychiatr Psychother 2005;53:16–39. 15. Torgalsboen AK. Sustaining full recovery in schizophrenia after 15 years: does resilience matter? Clin Schizophr Relat Psychoses 2012;5:193–200. 16. Malberg JE, Schechter LE. Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs. Curr Pharm Des 2005;11:145–155. 17. Nater UM, Rohleder N. Salivary alpha-amylase as a noninvasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology 2009; 34:486–496. 18. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization, 1992. 19. Ikai S, Uchida H, Suzuki T, et al. Effects of yoga therapy on postural stability in patients with schizophreniaspectrum disorders: a single-blind randomized controlled trial. J Psychiatr Res 2013;47:1744–1750. 20. Ahern NR, Kiehl EM, Sole ML, Byers J. A review of instruments measuring resilience. Issues Compr Pediatr Nurs 2006;29:103–125. 21. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276. 22. Inada T. [Evaluation and Diagnosis of Drug-Induced Extrapyramidal Symptoms: Commentary on the DIEPSS and Guide to Its Usage]. Tokyo: Seiwa Press, 1996.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
830
23. Suzuki T, Uchida H, Nomura K, et al. Novel rating scales for schizophrenia—Targeted Inventory on Problems in Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Schizophr Res 2008;106:328–336. 24. Brooks R. EuroQol: the current state of play. Health Pol 1996;37:53–72. 25. Inagaki A, Inada T, Fujii Y. [Dose Equivalents of Psychotropic Drugs]. Tokyo: Seiwa Press, 1999. 26. Inagaki A, Inada T. [Dose equivalence of psychotropic drugs. Part XXI: dose equivalence of novel antipsychotics.] Jpn J Clin Psychopharmacol 2008;11:887–890. 27. Shetty V, Zigler C, Robles TF, et al. Developmental validation of a point-of-care, salivary alpha-amylase biosensor. Psychoneuroendocrinology 2011;36:193–199. 28. Vancampfort D, De Hert M, Knapen J, et al. State anxiety, psychological stress and positive well-being responses to yoga and aerobic exercise in people with schizophrenia: a pilot study. Disabil Rehabil 2011;33:684–689. 29. Khalsa SB, Hickey-Schultz L, Cohen D, et al. Evaluation of the mental health benefits of yoga in a secondary school: a preliminary randomized controlled trial. J Behav Health Serv Res 2012;39:80–90. 30. Noggle JJ, Steiner NJ, Minami T, Khalsa SB. Benefits of yoga for psychosocial well-being in a US high school curriculum: a preliminary randomized controlled trial. J Dev Behav Pediatr 2012;33:193–201. 31. Michalsen A, Grossman P, Acil A, et al. Rapid stress reduction and anxiolysis among distressed women as a consequence of a three-month intensive yoga program. Med Sci Monit 2005;11:CR555–561. 32. Gururaja D, Harano K, Toyotake I, Kobayashi H. Effect of yoga on mental health: comparative study between
IKAI ET AL.
33.
34.
35.
36.
37.
young and senior subjects in Japan. Int J Yoga 2011;4: 7–12. Ieda M, Miyaoka T, Wake R, et al. Evaluation of autonomic nervous system by salivary alpha-amylase level and heart rate variability in patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 2014;264:83–87. Green MJ, Matheson SL, Shepherd A, et al. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 2011;16:960– 972. Pan NL LC, Jiang MJ, HP Lu, CL Wang, AM Huang. Serum levels of brain derived neurotrophic factor before and after the practice of Sudarshan Kriya. Proceedings World Conference Expanding Paradigms: Science, Consciousness and Spirituality. New Delhi, India: All India Institute of Medical Sciences. 2006:156–160. Naveen GH, Thirthalli J, Rao MG, et al. Positive therapeutic and neurotropic effects of yoga in depression: a comparative study. Ind J Psychiatry 2013;55(Suppl 3): S400–404. Favalli G, Li J, Belmonte-de-Abreu P, et al. The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 2012;46:1–11.
Address correspondence to: Saeko Ikai, MD Department of Neuropsychiatry Keio University School of Medicine 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582 Japan E-mail: [email protected]
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 20, Number 11, 2014, pp. 823–830 ª Mary Ann Liebert, Inc. DOI: 10.1089/acm.2014.0205
Original Articles
Effects of Weekly One-Hour Hatha Yoga Therapy on Resilience and Stress Levels in Patients with Schizophrenia-Spectrum Disorders: An Eight-Week Randomized Controlled Trial Saeko Ikai, MD,1 Takefumi Suzuki, MD, PhD,1,2 Hiroyuki Uchida, MD, PhD,1,3 Juri Saruta, DDS, PhD,4,5 Keiichi Tsukinoki, DDS, PhD,4,5 Yasuo Fujii, MD, PhD,6 and Masaru Mimura, MD, PhD1
Abstract
Objective: To examine the effects of Hatha yoga therapy on resilience, brain-derived neurotrophic factor (BDNF) levels, and salivary alpha amylase (SAA) activity in patients with schizophrenia-spectrum disorders. Design and participants: Single-blinded, randomized controlled study in which outpatients with schizophrenia or related psychotic disorders (according to International Classification of Diseases, 10th Revision) were randomly assigned to a yoga or a control group. Setting: November 2012–April 2013 at Yamanashi Prefectural Kita Hospital, Japan. Interventions: In the yoga group, patients received weekly 1-hour Hatha yoga sessions, in addition to regular treatment, for 8 weeks. Those in the control group underwent regular treatment, which included a daycare rehabilitation program. Outcome measures: Assessments included the 25-item Resilience Scale (RS), Positive and Negative Syndrome Scale (PANSS), plasma and salivary BDNF level, and SAA activity. Results: Fifty patients participated (25 in each group; mean age – standard deviation, 50.9 – 11.3 years; mean duration of illness, 25.0 – 10.3 years; mean total PANSS score, 78.2 – 17.3). No significant differences in changes in any variable from baseline to week 8 were found between the two groups (changes in the yoga group versus the control group: RS score, - 1.6 – 19.9 versus 0.3 – 17.2; PANSS score, 0.5 – 12.0 versus 5.0 – 15.6; plasma BDNF, 41.6 – 377.0 pg/dl versus 73.4 – 346.0 pg/dl; SAA, - 26.2 – 72.6 kU/l versus - 13.8 – 68.0 kU/l, respectively). Conclusions: Adjunct yoga therapy showed no positive changes in resilience level or stress markers. Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy. oga has been practiced for several millennia1 and includes a variety of movements and poses that are performed in coordination with breath control, meditation, relaxation, and lifestyle. As such, yoga is expected to improve not only physical conditions but also mental wellness.2 For example, recent evidence obtained from randomized controlled trials indicated benefits of yoga therapy for patients with schizophrenia; psychiatric symptoms improved with this intervention in addition to ongoing antipsychotic
Y
treatment,3–6 although the data in this field still remain scarce and inconclusive.7 Moreover, yoga has reduced stress levels,8–10 which is especially relevant for patients with schizophrenia given the close relationship between stress and relapse in this patient population.11 ‘‘Resilience’’ is defined as a positive adaptation and maintenance of competent function even in the face of prolonged stress and adversities.12,13 Some individuals, despite marked negative circumstances and risk factors,
1
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Department of Psychiatry, Inokashira Hospital, Tokyo, Japan. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 4 Department of Oral Sciences, Kanagawa Dental University Graduate School of Dentistry, Kanagawa, Japan. 5 Research Institute of Salivary Gland and Health Medicine, Kanagawa Dental University Graduate School of Dentistry, Kanagawa, Japan. 6 Department of Neuropsychiatry, Yamanashi Prefectural Kita Hospital, Yamanashi, Japan. 2 3
823
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
824
remain healthy or easily recover from adverse events, while others under similar conditions seem vulnerable to disorders.14 Pathoetiology of schizophrenia has conventionally been investigated to seek new treatment approaches that will normalize the aberrant conditions. However, while such a traditional approach is valid, it is also critically important to focus on patients’ resilience in order to understand mechanisms of recovery of this illness. In fact, good resilience increases the chance of long-term recovery in patients with schizophrenia.15 Thus, the concept of resilience has recently gained wide attention. Because practicing yoga could reduce stress levels, it would be beneficial to test the idea that such therapy may have some beneficial effects on resilience levels in patients with schizophrenia. No existing studies appear to have studied this topic. Stress suppresses neurogenesis through a process that involves brain-derived neurotrophic factor (BDNF).16 Salivary alpha amylase activity (SAA) levels increasingly can be used as an accessible measure of sympathetic nervous system reactivity to stressors.17 However, no data are available on yoga’s effects on those measurable biological stress markers. On the basis of this background, the current 8-week, single-site, single-blind, randomized controlled trial evaluated the effects of adjunctive weekly Hatha yoga therapy on resilience level, BDNF, and SAA activity in outpatients with schizophrenia-spectrum disorders. Materials and Methods Study design
In this study, eight weekly sessions of Hatha yoga therapy were added to ongoing regular psychopharmacologic treatment, together with a follow-up visit after an additional 8 weeks. This study was conducted in Yamanashi Prefectural Kita Hospital, Yamanashi, Japan, between November 2012 and April 2013. The hospital’s institutional ethics board approved the study, and all participants provided written informed consent after being given a full description of the study. The study was registered at the University Medical Information Network Clinical Trial Registry (Identifier: UMIN000009305). Participants
Outpatients who were diagnosed with schizophrenia or related psychotic disorders (F20–F25 according to the International Classification of Diseases, 10th edition),18 were age 18 years or older, had been receiving the same medications for the 8 weeks preceding entry, and were registered in the daycare center in the hospital were approached and asked to participate in this study. Patients who were incapable of providing consent or suffered from active alcohol abuse or other psychiatric comorbidities were excluded; to ensure representativeness of the sample, no other exclusion criteria were applied. Medications were kept constant by the patients’ treating psychiatrists throughout the study period unless a change was clinically indicated. Intervention
The patients were randomly assigned to either a yoga therapy group or treated-as-usual group. The randomization was performed by using sealed envelopes prepared by physicians at Yamanashi Prefectural Kita Hospital who were not involved in
IKAI ET AL.
this study. An envelope method was used to randomly divide the patients into two groups. A simple randomization list with no special stratification or blocks was made by using a computer program. One of the four physicians opened the envelopes after the baseline assessment. Patients assigned to the yoga group received a weekly 1-hour session of Hatha yoga therapy between 9:40 and 10:40 a.m. on Mondays in the hospital gymnasium for a total of eight sessions. Participants were asked not to perform selfpractice of yoga therapy at home. The sessions were provided as an adjunct to regular ambulatory treatment by one of the authors, who was an instructor with a master’s degree in Hatha yoga. Each session consisted of gentle yoga stretches and simple movements in coordination with breathing (gentle movements of major muscle groups), asana (twisting poses and standing poses), deep relaxation, and breathing exercises.19 After the completion of the 8-week intervention, patients received treatment as usual but did not receive any yoga therapy until the follow-up assessment was performed. Patients in the control group attended a weekly regular daycare program (which provided social skills and walking) for 8 weeks. After the completion of the 8-week observation period, the patients in this group were allowed to attend Hatha yoga sessions upon request, which was offered outside the present trial. Outcome measures
The primary outcome measure was resilience level at week 8 assessed with the 25-item Resilience Scale.20 This scale measures the degree of individual resilience and is considered to represent a positive personality characteristic that enhances individual adaptation. The scale covers five factors of resilience: purpose, perseverance, self-reliance, equanimity, and existential aloneness. Items are scored on a 7-point scale ranging from 1 = disagree to 7 = agree, with possible scores ranging from 25 to 175; a higher score indicates greater individual resilience. The secondary outcome measures included fasting blood glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, plasma and salivary BDNF, and SAA. These measurements took place between 9:00 a.m. and 12:00 p.m. at baseline and week 8 in both groups. The following assessments were also performed: the Positive and Negative Syndrome Scale (PANSS),21 the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS),22 the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz),23 and the EuroQol-5 dimensions (EQ-5D) classification system.24 Follow-up assessments at week 16 in the yoga group included the RS, fasting blood glucose, total cholesterol chol, HDL cholesterol, LDL cholesterol, triglycerides, BDNF, SAA, and the EQ-5D. All assessments were performed by trained psychiatrists who were blind to the patients’ allocations and were not involved in the yoga therapy. Information collected included sex, age, duration of illness, body–mass index, physical comorbidities, waist circumference, and psychotropic medications. Daily doses of antipsychotics, including depot antipsychotics, were converted to chlorpromazine equivalents.25,26 Venous blood samples were centrifuged at 3000 rpm for 10 minutes. All plasma samples were then stored at - 30
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
YOGA AND RESILIENCE IN SCHIZOPHRENIA
825
until analyzed. Plasma and salivary concentrations of BDNF were measured according to the procedure supplied by the manufacturer (CYT306; Millipore Corp., Bedford, MA). To quantify SAA, a salivary alpha-amylase monitor (NIPRO, Osaka, Japan) was used. This biosensor is composed of a disposable test strip and a hand-held reader. The precision (coefficient of variation) was reported as 8.1%, and its repeatability has measurement reliability.27 The saliva sample was collected by dipping a sampling strip under the tongue for 30 seconds. The level of SAA was used as a proxy of acute stress.17
interest between the yoga and control groups. In addition, repeated-measures analysis of variance was used to compare the variables between baseline and weeks 8 and 16 in the yoga group. When appropriate, post hoc analyses were performed with Bonferroni correction. The Pearson test was used to examine correlations in the changes of the variables. Main analyses were performed by using a last-observationcarried-forward method. Completer analysis was also used. All tests were two tailed, and p < 0.05 was considered to represent a statistically significant difference. Results
Statistical analyses
No formal sample size calculation was performed because there has been no study on which to base sample size estimation. Statistical analyses were carried out using SPSS software, version 20 (IBM Corp., Armonk, NY). Patients’ baseline characteristics were compared between the two groups by using the chi-square test or the independent t-test. The Mann-Whitney U test was used for age, duration of illness, body–mass index, dose of antipsychotics, FACT-Sz score, DIEPSS score, EQ-5D (index), SAA, triglycerides, HDL cholesterol, fasting blood glucose, and plasma and salivary BDNF because these were not distributed normally (according to the Shapiro-Wilk test of normality). Analysis of covariance (ANCOVA) with baseline values as covariates was used to compare changes at week 8 in the variables of
Patient characteristics
Eighty-one outpatients with schizophrenia-spectrum disorders registered in the daycare center were approached for possible participation in this study. Nineteen outpatients declined to participate because of their schedules and 12 had little interest in yoga therapy. Thus, 50 outpatients agreed to participate in this study and were allocated to either the yoga therapy group (n = 25) or the control group (n = 25). Characteristics and disposition of participants are shown in Table 1 and Figure 1, respectively; there were no significant differences at baseline between those two groups. All participants were Japanese. Forty-one patients had schizophrenia and 9 had schizoaffective disorder. Physical comorbidities were as follows: hyperlipidemia (14%; n = 7),
Table 1. Demographic and Clinical Characteristics of Patients Characteristic Age (y) Men, n (%) Duration of illness (y) Body–mass index (kg/m2) Dose of antipsychotics (CPZE mg/d) Waist circumference (cm) PANSS Total score Positive symptom score Negative symptom score General psychopathology score FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score Resilience Scale score SAA (kU/L) Total cholesterol (mg/dL) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL)
Yoga group (n = 25)
Control group (n = 25)
53.5 – 9.9 16 (64.0) 25.3 – 9.6 24.6 – 6.2 659.3 – 386.2 92.3 – 10.7
48.2 – 12.3 17 (68.0) 24.7 – 11.1 24.5 – 3.1 733.5 – 432.5 90.6 – 11.8
NA NA NA NA NA 0.52
0.14 0.77 0.76 0.78 0.71 0.42
76.3 – 18.5 15.6 – 5.1 21.1 – 5.3 39.6 – 12.1 56.7 – 11.8 1.5 – 1.9 0.86 – 0.24 71.3 – 18.7 114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.0
80.2 – 16.1 16.9 – 5.1 21.1 – 4.4 41.7 – 8.5 56.8 – 6.2 2.2 – 2.9 0.80 – 0.23 68.8 – 17.2 109.2 – 30.4 123.9 – 127.7 198.0 – 33.5 159.7 – 74.3 120.7 – 29.4 49.6 – 16.5 123.2 – 34.7 274.1 – 471.0 412.1 – 825.6
- 0.78 - 0.84 0.02 0.16 NA NA NA 0.50 0.61 NA 0.34 NA - 0.81 NA NA NA NA
0.44 0.41 0.98 0.68 0.43 0.46 0.64 0.50 0.91 0.99 0.63 0.69 0.70 0.26 0.61 0.90 0.91
t
p-Value
Unless otherwise noted values are expressed as the mean – standard deviation. Group differences were compared by using chi-square test, independent t-test, or the Mann-Whitney test (see text for details). BDNF, brain-derived neurotrophic factor; CPZE, chlorpromazine equivalent; DIEPSS, Drug Induced Extrapyramidal Symptoms Scale; EQ-5D, EuroQol 5 dimensions; FACT-Sz, Functional Assessment for Comprehensive Treatment of Schizophrenia; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NA, not applicable; PANSS, Positive and Negative Syndrome Scale; SAA, salivary alphaamylase activity; TG, triglyceride; VAS, visual analogue scale.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
826
IKAI ET AL.
FIG. 1. Flow of patients through the study.
hypertension (12%; n = 6), diabetes mellitus (2%; n = 1), hyperuricemia (2%; n = 2), and arrhythmia (2%; n = 2). Antipsychotic medications at baseline were olanzapine (32%; n = 16), risperidone (20%; n = 10), fluphenazine (14%; n = 7), aripiprazole (10%; n = 5), clozapine (8%; n = 4), levomepromazine (4%; n = 2), paliperidone (4%; n = 2), bromperidol (2%; n = 2), chlorpromazine (2%; n = 2), haloperidol (2%; n = 2), and sulpiride (2%; n = 2). Twenty patients (40.0%) were receiving two or more antipsychotics. Medication adherence was acceptable judging from patients’ interview for both groups. Only one participant (in the control group) experienced a change in the medication regimen from paliperidone, 3 mg/d, to risperidone, 4 mg/d, because of worsening delusions. Treatment outcomes
Seven participants (28.0%) in each group prematurely withdrew from the study. The reasons of withdrawal were refusal to continue (6 participants in the yoga group and 5 participants in the control group), relapse (1 participant in the control group), and difficulty matching the schedule (1 each in the yoga and control groups). No significant differences were observed in changes from baseline to week 8 in any of the variables of interest in both groups (Table 2). The ANCOVA with baseline values as covariates also showed no significant differences in changes in any of the variables of interest between the groups (Table 3). Additionally, no clinical gains were observed with this intervention, as indicated in Table 4. In the yoga group, there was a modest correlation between the changes from the baseline to week 8 in the SAA activity and the RS (c = 0.403; p = 0.046), but they were not significantly correlated in the control group (c = 0.203; p = 0.158). As for the follow-up assessment at week 16 in the yoga group, only SAA significantly decreased compared with the baseline according to repeated-measures analysis of
variance (Table 4); however, this difference was no longer seen after Bonferroni correction. Completer analysis
Results of completer analysis are shown in the Supplementary Tables S1–S4 (Supplementary Data are available online at www.liebertpub.com/acm). Briefly, significant group differences were observed only in total PANSS score (mean – standard deviation: yoga group, 73.5 – 18.0 to 73.5 – 15.2; control group, 81.4 – 17.7 to 88.7 – 20.6) and general psychopathology score (yoga group, 38.1 – 13.0 to 36.9 – 8.0; control group, 42.3 – 9.5 to 46.6 – 14.3) with ANCOVA. At the follow-up assessment at week 16 in the yoga group, only SAA showed a significant decrease, which is consistent with the results of the last-observation-carried-forward method. Discussion Main findings
To the authors’ knowledge, this is the first study to assess the effect of Hatha yoga therapy on resilience, plasma and salivary BDNF, and SAA activity in patients with schizophrenia-spectrum disorders. Contrary to expectation, no variables significantly improved after the 8-week yoga intervention. However, these negative findings provide insights into improving the format and design of future yoga therapies, including frequency and duration, to achieve clinical gains in patients with schizophrenia discussed below. Such improvements might be beneficial given the past positive evidence of yoga therapy in improving physical and psychological conditions in other populations.3–6,28 Yoga therapy and resilience
Past evidence on yoga and resilience in healthy people and psychiatric patients is scarce and preliminary. Khalsa
YOGA AND RESILIENCE IN SCHIZOPHRENIA
827
Table 2. Analysis of Covariance for Resilience, Biological Markers, Psychopathology, Extrapyramidal Symptoms, and Quality of Life Yoga group (n = 25)
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dl) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) PANSS Total score Positive symptom Negative symptoms General psychopathology FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score
Control group (n = 25)
Baseline
Week 8
Baseline
Week 8
114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.0
112.7 – 22.6 109.2 – 111.6 199.8 – 32.4 162.8 – 137.2 117.1 – 31.8 54.8 – 17.4 122.0 – 34.4 190.7 – 598.8 208.3 – 342.5
109.2 – 30.4 123.9 – 127.7 198.0 – 33.5 159.7 – 74.3 120.7 – 29.4 49.6 – 16.5 123.2 – 34.7 274.1 – 471.0 412.1 – 825.6
109.5 – 29.2 110.1 – 133.1 199.7 – 35.6 160.1 – 73.2 119.8 – 27.8 49.7 – 13.8 119.6 – 24.4 347.6 – 652.2 383.3 – 561.2
76.3 – 18.5 15.6 – 5.1 21.1 – 5.3 39.6 – 12.1 56.7 – 11.8 1.5 – 1.9 0.86 – 0.24 71.3 – 18.7
76.8 – 16.2 16.0 – 4.6 21.8 – 5.7 39.0 – 16.2 55.8 – 10.4 1.4 – 1.8 0.82 – 0.25 72.8 – 17.1
80.2 – 16.1 16.9 – 5.1 21.1 – 4.4 41.7 – 8.5 56.8 – 6.2 2.2 – 2.9 0.80 – 0.23 68.8 – 17.2
81.8 – 25.5 18.0 – 4.9 22.5 – 5.0 44.7 – 13.3 56.3 – 8.1 2.9 – 2.8 0.67 – 0.31 64.8 – 20.4
F-Value
p-Value
0.004 0.289 0.127 1.420 1.297 0.047 0.996 0.053 0.569
0.948 0.594 0.723 0.240 0.262 0.829 0.324 0.819 0.455
2.256 1.028 0.516 2.558 - 0.348 3.570 3.009 2.172
0.140 0.316 0.476 0.117 0.730 0.065 0.089 0.147
Unless otherwise noted, values are expressed as the mean – standard deviation.
and colleagues reported that the resilience level, measured with the RS, slightly improved with yoga while most outcome measures, inclusive of the RS, exhibited a pattern of worsening in the control group over time among adolescents in secondary school.29 Preventive benefits in psychosocial well-being were also reported when Kripalu yoga (which consists of three stages: willful practice, surrender, and
meditation in motion) was practiced among students in 11th and 12th grades, although the RS scores did not significantly change.30 On the other hand, women with mental distress significantly improved on measures of stress and psychological outcome after a 3-month yoga intervention.31 Further, yoga therapy decreased SAA activity in both elderly and young people,32 in whom a decrease in SAA is
Table 3. Changes in Resilience, Biological Markers, Psychopathology, Extrapyramidal Symptoms, and Quality of Life in Yoga and Control Groups from Baseline to Week Eight Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dl) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) PANSS Total score Positive symptom Negative symptoms General psychopathology FACT-Sz score DIEPSS total score EQ-5D index EQ-5D VAS score
Yoga group (n = 25)
Control group (n = 25)
p-Value
- 1.6 – 19.9 - 26.2 – 72.6 - 1.7 – 33.2 - 41.7 – 178.5 3.9 – 15.0 - 0.1 – 5.7 7.5 – 26.7 41.6 – 377.0 - 7.8 – 108.3
0.3 – 17.2 - 13.8 – 68.0 1.9 – 13.6 0.7 – 56.5 - 2.1 – 14.5 0.1 – 5.7 - 3.6 – 28.9 73.4 – 346.0 - 28.1 – 611.7
0.83 0.35 0.44 0.47 0.19 0.97 0.63 0.23 0.41
0.5 – 12.0 0.4 – 2.0 0.7 – 2.7 - 0.6 – 9.1 - 0.9 – 4.0 - 0.1 – 1.4 - 0.03 – 0.15 1.5 – 16.4
5.0 – 15.6 0.8 – 3.8 1.4 – 4.4 2.7 – 11.3 - 0.4 – 5.7 0.6 – 1.5 - 0.11 – 0.26 - 4.0 – 17.3
0.43 0.82 0.51 0.58 0.29 0.66 0.33 0.63
Unless otherwise noted, values are expressed as the mean – standard deviation. Group differences were compared by using the MannWhitney test.
828
IKAI ET AL.
Table 4. Repeated-Measures Analysis of Variance in Yoga Group (n = 25)
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Variable Resilience Scale score SAA (kU/L) Total cholesterol (mg/dL) TG (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Fasting blood glucose (mg/dL) Plasma BDNF (pg/dL) Salivary BDNF (pg/dL) EQ-5D index EQ-5D VAS score
Baseline
Week 8
Week 16
F-Value
p-Value
114.3 – 29.7 135.3 – 133.1 201.5 – 38.1 206.8 – 30.0 112.7 – 33.6 54.7 – 17.7 114.5 – 21.3 149.1 – 258.6 216.1 – 384.6 0.86 – 0.24 71.3 – 18.7
112.7 – 22.6 109.2 – 111.6 199.8 – 32.4 162.8 – 137.2 117.1 – 31.8 54.8 – 17.4 122.0 – 34.4 190.7 – 598.8 208.3 – 342.5 0.83 – 0.25 72.8 – 17.1
118.0 – 28.0 96.2 – 86.7 200.6 – 35.7 163.5 – 146.6 117.8 – 31.9 56.9 – 17.1 121.6 – 24.7 69.4 – 83.9 179.3 – 324.7 0.86 – 0.24 71.3 – 20.6
1.420 3.541 0.043 1.214 1.051 1.642 1.044 1.169 1.563 0.929 0.193
0.252 0.037a 0.958 0.306 0.359 0.205 0.360 0.319 0.220 0.402 0.825
Unless otherwise noted, values are expressed as the mean – standard deviation. a Significant difference ( p < 0.05).
considered to represent an attenuated sympathetic tone. Relevant here is a finding that the SAA level was higher in patients with schizophrenia than in healthy people.33 In the present study, the RS scores did not change in either group. The lack of significant changes may be attributable to characteristics of the sample, including their relatively older mean age compared with previous studies. Moreover, the mean duration of illness was as long as approximately 25 years, which represents the chronicity of the illness in the participants and may limit any room for improvements in resilience levels in the present study. SAA activity as an index of acute stress also did not change. However, this study assessed outpatients in the chronic stage of the illness, and any extrapolation of our findings to other patient populations, such as younger patients with acute disease or older patients, should be done with caution. Additionally, we did not evaluate more exhaustive parameters of stress and autonomic functioning, including hypothalamic-pituitary-adrenal axis hormones, heart rate variability, positional blood pressure, and baroreceptor sensitivity. Yoga therapy and BDNF
BDNF is a trophic factor involved in the development of the brain and may influence neuroplasticity in schizophrenia.34 Stress and depression suppress neurogenesis through a process that probably involves this substance.16 Interventions that reportedly increase the BDNF level, such as exercise and antidepressant treatment, may help preserve brain function. In this context, practice of Sudarshan Kriya yoga increased serum levels of BDNF.35 In a study on the effect of yoga on BDNF levels among depressed patients in India, Naveen et al.36 observed that the change in BDNF did not significantly differ across three groups (i.e., yoga only, yoga and antidepressants, and antidepressants only). However, no studies have addressed this topic in patients with schizophrenia to date. In the current study, levels of both plasma and salivary BDNF did not significantly change. The study did not control for dose or type of antipsychotics. In a review, Favalli et al. suggested that typical antipsychotics decrease serum BDNF levels while atypical counterparts maintain or increase the levels.37 As such, use of various antipsychotics may have affected the current results. Additionally, a recent
meta-regression showed the evidence of lowered levels of brain BDNF in patients with schizophrenia as they grow older;34 the current participants were experiencing a relatively chronic course of their illness, with a mean illness duration of 25.0 – 10.3 years. Recommendations for future studies
Several points should be considered in planning future studies. The first concerns duration and intensity of the yoga therapy. In a previous study, the authors focused on the effects of yoga on postural sway in patients with chronic schizophrenia.19 Although the yoga intervention (i.e., a weekly 1-hour yoga session for 8 weeks) improved postural instability, it was insufficient to improve resilience and stress levels in this study. To further optimize yoga therapy, longer duration or greater intensity may be necessary in future trials. Second, intensity of yoga sessions should be considered; a once-a-week session may be insufficient. Third, the content of the yoga therapy may need to be adjusted for an elderly population to accommodate their physical strength and range of joint motion. Fourth, the data from multisite studies of yoga therapy in psychiatric patients are very scarce. Further yoga studies should deal with many participants from multiple institutions with diverse cultural/ethnic backgrounds. Finally, it is impossible to conduct double-blind studies with yoga, thereby necessitating more mechanistic research.2 Limitations
Apart from the issues already discussed above, several other limitations should be noted. First, this study was limited by its small sample size (n = 50) and lack of formal sample size calculation. This may have limited the statistical power to detect any possible differentials in resilience, BDNF, and SAA between the groups and thus makes the work preliminary. Second, the results should be interpreted in the context of type, duration, and intensity of the Hatha yoga intervention in this study. The yoga sequence involved different types of posture in this study. The effect of yoga therapy on psychological or pathological scales might be due to the modified yoga therapy used by one author. Finally, most participants in this study had long been taking various antipsychotics
YOGA AND RESILIENCE IN SCHIZOPHRENIA
that potentially affect metabolic markers in a negative manner, which would make it difficult to capture any positive changes in a short study.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
Conclusions
This appears to be the first study to focus on the effect of Hatha yoga therapy on resilience, BDNF, and SAA activity in patients with schizophrenia. The results were negative. However, these results alone should not discourage further critical appraisal of this intervention because of its theoretical benefits and past positive evidence in a variety of settings and populations. In light of the paucity of the available data, these results emphasize the need for further investigations on the potential benefits of yoga therapy in patients with schizophrenia. Acknowledgments
We gratefully acknowledge the assistance of the regular day-care program staff in Yamanashi Prefectural Kita Hospital. The authors thank Drs. Ryoji Miyata, Akiko Kano, Fuminari Misawa, Mihoko Kobayashi, Hirokazu Shida, Waka Nogami, Hideaki Tani, Nobuhiro Nagai, Tatsuichiro Takahashi, Maho Hasebe, Toru Yamashita, Minako Sato, Hisashi Kida, Ryosuke Tarumi, Gentaro Miura, Saiko Ema, and Hodaka Yaegashi; Ms. Ai Otani; Ms. Aki Tozawa; and Ms. Atsuko Ikubo for their continuous support. Author Disclosure Statement
Dr. Ikai has received manuscript fees or speaker’s honoraria from Dainippon Sumitomo, Novartis, and Janssen Pharmaceutical within the past 3 years. Dr. Suzuki has received manuscript or speaker’s fees from Astellas, Dainippon Sumitomo, Eli Lilly, Elsevier Japan, Janssen, Meiji Seika, Novartis, Otsuka, and Weily Japan. Dr. Uchida has received grants from Astellas Pharmaceutical, Eisai, Otsuka Pharmaceutical, GlaxoSmithKline, Shionogi, DainipponSumitomo Pharma, Eli Lilly, Mochida Pharmaceutical, Meiji-Seika Pharma, Janssen Pharmaceutical, and Yoshitomi Yakuhin and speaker’s honoraria from Otsuka Pharmaceutical, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Dainippon-Sumitomo Pharma, Meiji-Seika Pharma, Abbvie, and Janssen Pharmaceutical within the past 3 years. Dr. Fujii has received speaking fees from Janssen Pharmaceutical and Eli Lilly within the past 3 years. Dr. Mimura has received grants and/or speaker’s honoraria from Asahi Kasei Pharma, Astellas Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji-Seika Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi Pharma, and Yoshitomi Yakuhin within the past 3 years. References
1. Iyengar B. Light on Yoga. New York: Schocken Books, 1996. 2. Balasubramaniam M, Telles S, Doraiswamy PM. Yoga on our minds: a systematic review of yoga for neuropsychiatric disorders. Front Psychiatry 2012;3:117.
829
3. Behere RV, Arasappa R, Jagannathan A, et al. Effect of yoga therapy on facial emotion recognition deficits, symptoms and functioning in patients with schizophrenia. Acta Psychiatr Scand 2011;123:147–153. 4. Duraiswamy G, Thirthalli J, Nagendra HR, Gangadhar BN. Yoga therapy as an add-on treatment in the management of patients with schizophrenia—a randomized controlled trial. Acta Psychiatr Scand 2007;116:226–232. 5. Visceglia E, Lewis S. Yoga therapy as an adjunctive treatment for schizophrenia: a randomized, controlled pilot study. J Altern Complement Med 2011;17:601–607. 6. Xie J, Lin Y, Guo C, Chen F. Study of influences of yoga on quality of life of schizophrenic inpatients. J Nursing (China). 2006;13:9–11. 7. Cramer H, Lauche R, Klose P, et al. Yoga for schizophrenia: a systematic review and meta-analysis. BMC Psychiatry. 2013;13:32. 8. Brown RP, Gerbarg PL. Yoga breathing, meditation, and longevity. Ann N Y Acad Sci. 2009;1172:54–62. 9. Chong CS, Tsunaka M, Tsang HW, et al. Effects of yoga on stress management in healthy adults: a systematic review. Altern Ther Health Med 2011;17:32–38. 10. Li AW, Goldsmith CA. The effects of yoga on anxiety and stress. Altern Med Rev 2012;17:21–35. 11. Howes OD, McDonald C, Cannon M, et al. Pathways to schizophrenia: the impact of environmental factors. Int J Neuropsychopharmacol 2004;7 Suppl 1:S7–S13. 12. Lutha SS, Cicchetti D. The construct of resilience: implications for interventions and social policies. Dev Psychopathol 2000;12:857–885. 13. Yagi K. [Resilience in mental disorders—special reference to biological research.] Seishin Shinkeigaku Zasshi 2008; 110:770–775. 14. Schumacher J, Leppert K, Gunzelmann T, et al. The resilience scale—a questionnaire to assess resilience as a personality characteristic. Z Klin Psychol Psychiatr Psychother 2005;53:16–39. 15. Torgalsboen AK. Sustaining full recovery in schizophrenia after 15 years: does resilience matter? Clin Schizophr Relat Psychoses 2012;5:193–200. 16. Malberg JE, Schechter LE. Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs. Curr Pharm Des 2005;11:145–155. 17. Nater UM, Rohleder N. Salivary alpha-amylase as a noninvasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology 2009; 34:486–496. 18. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization, 1992. 19. Ikai S, Uchida H, Suzuki T, et al. Effects of yoga therapy on postural stability in patients with schizophreniaspectrum disorders: a single-blind randomized controlled trial. J Psychiatr Res 2013;47:1744–1750. 20. Ahern NR, Kiehl EM, Sole ML, Byers J. A review of instruments measuring resilience. Issues Compr Pediatr Nurs 2006;29:103–125. 21. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276. 22. Inada T. [Evaluation and Diagnosis of Drug-Induced Extrapyramidal Symptoms: Commentary on the DIEPSS and Guide to Its Usage]. Tokyo: Seiwa Press, 1996.
The Journal of Alternative and Complementary Medicine 2014.20:823-830. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 01/10/15. For personal use only.
830
23. Suzuki T, Uchida H, Nomura K, et al. Novel rating scales for schizophrenia—Targeted Inventory on Problems in Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Schizophr Res 2008;106:328–336. 24. Brooks R. EuroQol: the current state of play. Health Pol 1996;37:53–72. 25. Inagaki A, Inada T, Fujii Y. [Dose Equivalents of Psychotropic Drugs]. Tokyo: Seiwa Press, 1999. 26. Inagaki A, Inada T. [Dose equivalence of psychotropic drugs. Part XXI: dose equivalence of novel antipsychotics.] Jpn J Clin Psychopharmacol 2008;11:887–890. 27. Shetty V, Zigler C, Robles TF, et al. Developmental validation of a point-of-care, salivary alpha-amylase biosensor. Psychoneuroendocrinology 2011;36:193–199. 28. Vancampfort D, De Hert M, Knapen J, et al. State anxiety, psychological stress and positive well-being responses to yoga and aerobic exercise in people with schizophrenia: a pilot study. Disabil Rehabil 2011;33:684–689. 29. Khalsa SB, Hickey-Schultz L, Cohen D, et al. Evaluation of the mental health benefits of yoga in a secondary school: a preliminary randomized controlled trial. J Behav Health Serv Res 2012;39:80–90. 30. Noggle JJ, Steiner NJ, Minami T, Khalsa SB. Benefits of yoga for psychosocial well-being in a US high school curriculum: a preliminary randomized controlled trial. J Dev Behav Pediatr 2012;33:193–201. 31. Michalsen A, Grossman P, Acil A, et al. Rapid stress reduction and anxiolysis among distressed women as a consequence of a three-month intensive yoga program. Med Sci Monit 2005;11:CR555–561. 32. Gururaja D, Harano K, Toyotake I, Kobayashi H. Effect of yoga on mental health: comparative study between
IKAI ET AL.
33.
34.
35.
36.
37.
young and senior subjects in Japan. Int J Yoga 2011;4: 7–12. Ieda M, Miyaoka T, Wake R, et al. Evaluation of autonomic nervous system by salivary alpha-amylase level and heart rate variability in patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 2014;264:83–87. Green MJ, Matheson SL, Shepherd A, et al. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 2011;16:960– 972. Pan NL LC, Jiang MJ, HP Lu, CL Wang, AM Huang. Serum levels of brain derived neurotrophic factor before and after the practice of Sudarshan Kriya. Proceedings World Conference Expanding Paradigms: Science, Consciousness and Spirituality. New Delhi, India: All India Institute of Medical Sciences. 2006:156–160. Naveen GH, Thirthalli J, Rao MG, et al. Positive therapeutic and neurotropic effects of yoga in depression: a comparative study. Ind J Psychiatry 2013;55(Suppl 3): S400–404. Favalli G, Li J, Belmonte-de-Abreu P, et al. The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 2012;46:1–11.
Address correspondence to: Saeko Ikai, MD Department of Neuropsychiatry Keio University School of Medicine 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582 Japan E-mail: [email protected]
