Yoga and Aerobic Exercise in Psychosis
Condition: Psychotic Disorder
MeSH terms: Psychotic Disorders; Mental Disorders
Study type: Interventional

Summary: 
      The current study aims to evaluate the impacts of yoga and aerobic exercise on
      neuro-cognitive function, symptoms and brain changes in early psychosis. A total of 120
      female subjects who aging from 18-55 years old, and diagnosed with psychotic disorders within
      the past 5 years, will be randomized into 3 groups: 1) yoga therapy, 2) aerobic exercise, and
      3) waitlist group as the control. All groups will try to be kept consistent with their
      medication with no more than 25% change in their entry level dosage for at least six weeks.
      The primary outcomes of the present study will be neuro-cognitive changes; the secondary
      outcomes will be changes of brain structure and function.
    

Detailed description: 
      STUDY OBJECTIVES AND PURPOSE

      The present study aims to:

        1. Compare the effects of a 12-week integrated yoga therapy and 12-week aerobic exercise
           program (walking and cycling) on cognitive functions, brain structures and function in
           female psychosis patients.

        2. Compare the changes in physical fitness, clinical symptoms, body-perception, drug
           adherence, quality of life, and medicational side-effects.

      Descriptive data acquired from this study will contribute to a better understanding of the
      research implications and clinical applications of yoga and aerobic exercise.

      SUBJECTS This is a single-blinded, randomized, prospective study using psychopathological
      assessments, self-rating scales and imaging techniques. In this study, only female psychosis
      patients will be recruited from the Early Assessment Service for Young People with Psychosis
      Program (EASY) in Hong Kong, aiming to examine if there is any gender difference in
      comparison to the study by Pajonk et al. (2007), which selected only male subjects.

      Ideally, patients taking Benzodiazepine and anti-depressants will be excluded because of the
      influence of these drugs on the cognitive test results and hippocampal volume. If it is
      deemed impractical to completely exclude these patients, all subjects will at least be tried
      to keep consistent with their antipsychotic dosages, by not permitting more than a 25% change
      in dose in the first 6 weeks after commencement of the intervention.

      According to the data presented in the previous study (F. G. Pajonk et al., 2010), and using
      the statistical significant level 0.05 and the power 0.80, we calculated the sample size for
      cognitive assessment is 96 (32 each arm) and for brain imaging the sample required will be 48
      (16 each arm) (Noordzij et al., 2010). Considering the drop-out rate will be around 30%, we
      aim to recruit 120 patients (40 each arm) with half of them (20 each arm) undergoing MRI
      scanning.

      PROCEDURES Subjects will be screened by the clinicians in outpatient units in Hong Kong. They
      will be asked to sign the consent form when they agree to attend the study. Afterwards, they
      will be randomly divided into their respective intervention group. Each subject will be given
      a subject number, which will correspond to the group assignment. There will be two sessions
      of assessments. In the first session, all 120 subjects will be assessed by an investigator
      for their cognitive function, severity of symptoms, physical fitness, body-perception, drug
      adherence, quality of life, and medication side-effects. In the second session, the first 20
      subjects recruited into each group will undergo a structural MRI and functional MRI (resting)
      scan at baseline.

      Following the 12-week intervention, the subjects will repeat the same assessments and MRI
      scan as in the pre-intervention. Patients in waitlist will be provided another 3-month yoga
      or exercise course according to their willing after the waiting period. All the patients will
      be followed up for 18 months to assess the long-term effects of both interventions in
      cognition and symptoms.

      For the nature of the study, it is difficult to keep patients blind to group allocation, so
      that the study can hardly be a double-blinded trial but a single-blinded one. Two
      investigators will do the yoga training and aerobic exercise without knowing the assessment
      results. Two research assistants will be well-trained and recruited to do the assessment, and
      remains blind to treatment allocation.

      INTERVENTION PROGRAMS Yoga therapy: The yoga therapy consists of breathing control (10
      minutes), body postures (40-45 minutes), and relaxation (5 minutes). The yoga therapy will be
      carried out three times per week for around 60 minutes at each session. The yoga class will
      be operated with a size of about 5-10 participants according to the general small-group size
      with one instructor in the commercial yoga studios in Hong Kong. The body postures used in
      the present study are designed to cover all body parts to give the body an overall strength
      and stretching.

      Aerobic exercise: The aerobic exercise program will include walking on a treadmill (15-20
      minutes), and stationary cycling (25-30 minutes), followed by cool-down stretching afterwards
      (5 minutes). The aerobic exercise program will also take place three times per week for
      around 45-55 minutes at each session. The heart rate will be continuously monitored during
      exercise by a portable recorder aiming to maintain the heart rate in the range of 50-60% of
      the maximum VO2 value, yielding an exercise exertion level which is considered as a moderate
      intensity. The aerobic training session will be operated with a size of no more than 10
      participants.

      Discontiuation: yoga and aerobic exercise will be terminated if the subject reports any
      uncomfortable symptoms or loses interests in continuing. Discontinuation or non-participation
      will not affect the usual medical treatment and care, which they receive in the clinical
      settings.

      MEASURES The primary outcomes will be the cognitive tests (memory and attention). Severity of
      symptoms, physical fitness, and imaging data will be the secondary outcomes. For those
      patients who drop out during the study will be arranged to an additional assessment session
      at the withdrawal according to the willingness of the participants. Data of these drop-out
      patients will be used in the final analysis with the intention-to-treat (ITT) method.

      All measurements will be taken at baseline, 12 weeks (upon completion of intervention
      program) and at 18 months for all 120 subjects. MRI will be carried out at baseline and at 12
      weeks for the first 60 subjects recruited.

      I. Cognitive Functioning

        1. Wechsler Adult Intelligence Scale (WAIS): The current study uses Information sub-test
           and Digit-Symbol-Coding sub-test.

        2. Hong Kong List Learning Test (HKLLT): is a validated Chinese list-learning test (Chan et
           al., 2000). It provides assessments of the processes and organizational strategies
           involved in verbal learning.

        3. Digit Span Test: is a subtest of the Wechsler Adult Intelligence Scale-Revised.
           (Wechsler, 1981) It includes digit-span forwards (DF) and digit-span backwards (DB)
           tests.

      3. Letter Cancellation Test: subjects are asked to cancel the letter C and E as quickly as
      possible. Time, number of error and omission items will be recorded (Lezak, Howieson, &
      Loring, 1995).

      4. Stroop Color and Word Test: Assessment of cognitive flexibility, resistance to
      interference from outside stimuli, and the ability to suppress a prepotent verbal response.
      (Stroop, 1935) 5. Subjective Cognitive Impairment Scale (SCIS): A 31-item self-reported
      questionnaire designed to assess the subjective daily life cognitive impairments in patients
      with schizophrenia.

      II. Magnetic Resonance Imaging (MRI) The first 20 subjects recruited into each group will be
      scanned using a 3T scanner (Philips Achieva 3-Tesla Quasar). A T1-weighted, MPRAGE sequence
      (TE=3.2ms, TR=7.5ms, flip angle=7°, FOV 240mm×240 mm) of 155 consecutive slices will be
      acquired at sagittal view with a voxel size of 1mm×1mm×1 mm. A T2*-weighted EPI sequence will
      be used for functional magnetic resonance (fMRI) resting (TR/TE=2000/32ms, 32 slices) with a
      voxel size of 3x3x4mm.

      III. Physical Fitness:

        1. VO2 max (oxygen consumption): is the maximum capacity of an individual's body to
           transport and utilize oxygen during incremental exercise, which reflects the physical
           fitness of the individual.

        2. Body Mass Index (BMI).

        3. Dual-energy X-Ray Absorptiometry (DXA): assesses the body composition and bone density
           by passing a very low-level x-ray signal through the body.

        4. Sit-and-Reach test: is a common measure of flexibility, and specifically measures the
           flexibility of the lower back and hamstring muscles.

        5. Standing Balance Test: ask the person to stand on one foot for as long as possible. The
           test will be conducted with the person having their arms on their waist. Repeat the test
           on the other leg.

        6. Star Excursion Balance Test (SEBT) (Olmsted, Carcia, Hertel, & Shultz, 2002): The SEBT
           is performed with the subject standing at the center of a grid placed on the floor, with
           8 lines extending at 45。 increment from the center of the grid. The subject is asked to
           maintain a single-leg stance while reaching with the contralateral leg (reach leg) as
           far as possible along the appropriate vector. The distance from the center of the grid
           to the touch point is measured in centimeters.

      IV. Clinical Assessment

        1. Positive and Negative Syndrome Scale (PANSS).

        2. Calgary Depression Scale (CDS).

      V. Quality of Life The Short Form (36) Health Survey (SF-36).

      VI. Body-perception and Drug adherence measure

        1. Figure Rating Scale (FRS): there are seven male/female contour drawings, numbered "1" to
           "7", in increasing body size from left to right. Subjects are asked to choose one figure
           drawing that most accurately represents the size of their own bodies and then one that
           represents their desired figure.

        2. Cognitive Attitude towards Body Size: subjects are asked whether they think they are: 1)
           underweight; 2) of normal weight; or 3) overweight.

        3. Compliance Rating Scale (CRS): is used to assess medication adherence.

        4. Drug Attitude Inventory (DAI-30): assesses the subjects' attitude to the current
           medication they are taking.

      VII. Adverse event No current studies reported any physical or mental artifacts of yoga and
      aerobic exercise. There is some inherent potential risk of injury in any kind of physical
      activity. All exercises, both yoga and aerobic exercise, will be increased in a progressive
      manner to minimize this risk.

      The adverse event of the antipsychotics will be assessed by UKU, which is a new comprehensive
      rating scale for psychotropic drugs and a cross-sectional study of side effects in
      neuroleptic-treated patients.

      STATISTICS The Statistical Package for Social Sciences version 17.0 (SPSS 17.0 statistical
      package) will be used for the data analysis. Primary outcome variables will be cognition
      (Hong Kong List Learning Test), and structural imaging data (hippocampal and cingulate cortex
      volume).

      A mixed effects model of repeated measure will be used to compare the changes in cognition
      and clinical symptoms among the three groups. With mixed effects model, all available data of
      each subject at each time point will be used (R. Gueorguieva & J. H. Krystal, 2004). This
      strategy was based on the assumption that data were missing at random (Ralitza Gueorguieva &
      John H Krystal, 2004).With the unstructured covariance structure (Joe et al., 2009),
      differences between the three intervention groups over time were assessed with a Group x Time
      interaction term. Primary outcome measures (HKLLT, Digit Span test, Letter Cancellation test)
      will be first analyzed by including all three groups. For analyses meeting this criterion of
      statistical significance, follow-up, the priori comparisons of the active intervention groups
      with the waitlist group were carried out with the same strategy. All tests will be based on
      two-sided probabilities set at a significance level of 0.05. The Bonferroni correction
      procedure will be conducted to adjust for the multiple comparisons among groups.The effect
      size (Cohen's d) will be calculated as well to compare the therapeutic effects of yoga and
      aerobic exercise among the three groups.

      Image processing and analysis will be carried out with the software packages FSL4.1,
      Freesurfer 5.1 and SPM8. The primary outcomes of structural MRI data will be the changes of
      grey matter in hippocampus and prefrontal cortex. The primary outcomes of functional MRI data
      will be the activity changes in prefrontal cortex and cingulate cortex.
    

Intervention name(s): Yoga therapy; Aerobic exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 3 sessions per week for 12 weeks, total 36 sessions. Each session lasts around one hour.; 3 session per week for 12 weeks, total 36 sessions. Each session lasts around one hour.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: psychosis; yoga; aerobic exercise; memory; attention; neuro cognition