Effects of aerobic exercise on adolescents with subthreshold mood symptoms: a randomized psycho-education controlled trial
Gui-Yun Xu1, Kangguang Lin2
1 Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
2 Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University; Academician Workstation of Mood and Brain Sciences, Guangzhou Medical University, Guangzhou, Guangdong Province, China
|Date of Submission||04-Jul-2019|
|Date of Decision||08-Jul-2019|
|Date of Acceptance||23-Sep-2019|
|Date of Web Publication||12-Dec-2019|
Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University; Academician Workstation of Mood and Brain Sciences, Guangzhou Medical University, Guangzhou, Guangdong Province
Source of Support: None, Conflict of Interest: None
Background and objective: Adolescents often suffer from mood disorders and behavioral problems. Studies have shown that aerobic exercise can improve cognitive function, relieve depression, alleviate anxiety, and improve sleep. However, there have been few randomized controlled trials (RCT) evaluating the effects of aerobic exercise on cognition and mood symptoms in adolescents with subthreshold mood symptoms.
Participants and methods: This RCT will include 224 adolescents with subthreshold mood symptoms from a middle school in Guangzhou, Guangdong Province, China. Participants will be randomly allocated to exercise intervention or psycho-education controlled group (n = 112/group). Participants in the exercise intervention group will undergo aerobic exercise at an intensity of 50–70% of the maximum heart rate for 30 minutes per day, 4 days per week for 3 successive months. Participants in the psycho-education controlled group will perform activities including three sections of general psychological education (one section of group game, one section of poetry reading, and one section of singing entertainment). Protocol version: 1.0. The study protocol was approved by the Institutional Review Board of Guizhou Brain Hospital (Guangzhou Huiai Hospital) on October 26, 2016 (approval No. 2016-048).
Outcome measures: The primary outcome measure of this study is changes in depressive symptoms and neurocognitive function relative to baseline at the end of 12 weeks of intervention. Secondary outcome measures are anxiety symptoms, hypomanic symptoms, and change in brain connectivity relative to baseline at the end of 12 weeks of intervention.
Discussion: The effects of aerobic exercise in adolescents with subthreshold mood symptoms will be evaluated.
Registeration: This study was registered with ClinicalTrials.gov (identifier: NCT03300778) on October 3, 2017.
Keywords: adolescent; aerobic exercise; cognitive function; randomized controlled clinical trial; subthreshold mood symptoms
|How to cite this article:|
Xu GY, Lin K. Effects of aerobic exercise on adolescents with subthreshold mood symptoms: a randomized psycho-education controlled trial. Asia Pac J Clin Trials Nerv Syst Dis 2019;4:84-9
|How to cite this URL:|
Xu GY, Lin K. Effects of aerobic exercise on adolescents with subthreshold mood symptoms: a randomized psycho-education controlled trial. Asia Pac J Clin Trials Nerv Syst Dis [serial online] 2019 [cited 2020 Nov 25];4:84-9. Available from: https://www.actnjournal.com/text.asp?2019/4/4/84/271803
Funding: This study was financially supported by the National Key Special Subproject of "Research on Prevention and Control of Major
Chronic Non-infectious Disease" (No. 2016YFC1306702; to GYX).
| Introduction|| |
Teenagers face a variety of challenges such as campus bullying, traumatic experiences (e.g., sexual assault, physical abuse, death of a family member, and parental divorce), and internet addiction, which can lead to emotional and behavioral problems. About 30 million Chinese adolescents are thought to suffer from various emotional disorders and behavioral problems, and 30% of this population has experienced depression (Yang et al., 2015b; Zhuang and Chen, 2016; Shi et al., 2017; Liu et al., 2018). Depression associated with genetic or environmental risk factors in adolescents is believed to be associated with mild mania and bipolar disorder in subsequent years (Benarous et al., 2016). Emotional disorders refer to a group of diseases with various causes, characterized by significant and lasting emotional or mood changes. Patients with bipolar disorder generally have manic and depressive symptoms, and also exhibit abnormalities in emotion, cognition, and behavior. The prevalence of bipolar disorder in adolescents has increased dramatically over the past 20 years (Moreno et al., 2007; Ryles et al., 2017). Further, studies have shown that the risk of subthreshold depression and mania is higher in adolescents compared with other populations due to the instability of psychological state, the incompleteness of cognitive structure, and the asynchrony of physiological maturity and psychological development in this population (Piccinni et al., 2011; Rodríguez et al., 2012; Vandeleur et al., 2015).
Aerobic exercise has been found to lower blood pressure, control blood sugar, activate the immune system, improve blood circulation, and enhance the strength of cardiopulmonary tissues, bones, and muscles, as well as to reduce the risk of obesity, heart disease, hypertension, type 2 diabetes, osteoporosis, metabolic syndrome, stroke, and some types of cancer (Konopka and Harber, 2014; Yang et al., 2015a; Young et al., 2015; de Oliveira et al., 2017; Hashida et al., 2017; Miele and Headley, 2017; Pagonas et al., 2017) [Table 1]. However, few studies have examined whether aerobic exercise can benefit adolescents with subthreshold mood symptoms. In this randomized parallel controlled clinical trial, we will investigate the effects of 3 months of aerobic exercise on cognition and clinical symptoms in adolescents.
|Table 1: Clinical trials investigating the effects of aerobic exercise on adolescent’s psychological problems|
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| Participants and Methods|| |
This study is a randomized parallel controlled clinical trial.
This study will be performed at a middle school in Guangzhou, Guangdong Province, China. The study protocol was approved by the Institutional Review Board of Guizhou Brain Hospital (Guangzhou Huiai Hospital) on October 26, 2016 (approval No. 2016-048).
We recruited adolescents aged 12–14 years from a middle school in Guangzhou, China.
Both clinically-well adolescents and adolescents with subthreshold mood symptoms will be eligible.
- Participants have subthreshold mood symptoms defined as: Having two or more Diagnostic and Statistical Manual of Mental Disorders. 4th edtion (DSM-4; American Psychiatric Association, 1994). defined depressive symptoms lasting for at least 1 week but do not meet the criteria, one of which is a core symptom (such as loss of interest/happy activities, depression, etc.) that lasts at least 1 week; having two or more DSM-4 defined manic symptoms for at least 4 days but fall short of the criteria for hypomania or, having hypomanic syndrome that only last for 2–3 days;
- Aged 12–14 years, of either sex;
- Provision of written informed consent by the participants and their legal guardians.
Participants who meet one or more of the following conditions will be excluded from this study:
- Severe depression as defined by the DSM-4;
- History of an axis I psychiatric disorder;
- Neurological or musculoskeletal diseases/injuries;
- Uncontrollable cardiovascular or metabolic diseases that would interfere with the ability to run;
- Severe diseases that would interfere with the ability to run;
- Serious suicidal thoughts;
- Mental retardation;
- Participation in physical exercise or activities for 30 minutes per day, 4–5 times per week;
- Participation in another clinical trial.
Exercise intervention group: Participants will undergo 3 months of aerobic exercise at an intensity of 50–70% of the maximum heart rate (220 – patient age) for 30 minutes per day, 4 days per week.
Psycho-education controlled group: Adolescents will attend three sections of general psychological education (one section of group game, one section of poetry reading, and one section of singing).
Primary outcome measures
- Change in depressive symptoms relative to the baseline at the end of 12 weeks of treatment. Depressive symptoms will be evaluated using the Patient Health Questionnaire-9 items (PHQ-9). The PHQ-9 is a depression self-assessment scale with a full score of 27. A higher PHQ-9 score indicates more severe depression (Kroenke et al., 2001);
- Change in neurocognitive function relative to the baseline at the end of 12 weeks of treatment. Neurocognitive function will be evaluated using the MATRICS Consensus Cognitive Battery (MCCB). The MCCB is a 60-point cognitive assessment approved by the US Food and Drug Administration (FDA) for assessing schizophrenia, bipolar disorder, and other neuropsychiatric disorders. It is one of the designated tests for clinical trials of neuropsychiatric drugs. A lower MCCB score indicates more severe cognitive impairment (Shi et al., 2015).
Secondary outcome measures
- Change in anxiety symptoms relative to the baseline at 12 weeks of treatment. Anxiety symptoms will be evaluated using the Symptom Checklist-90 item (SCL-90). The SCL-90 is one of the most well-known mental health tests, and it is widely used to measure symptoms associated with mental and physiological disorders. A higher SCL-90 score indicates more severe symptoms, and a total score more than 160 suggests the presence of a physiological disorder (Chen et al., 2017);
- Change in hypomanic symptoms relative to the baseline at the end of 12 weeks of treatment. Hypomanic symptoms will be evaluated using the Hypomania Checklist-15 item (HCL-15). The HCL-15 is a 15-point scale, with a higher score indicating more severe hypomanic symptoms (He et al., 2014);
- Change in brain connectivity relative to the baseline at the end of 12 weeks of treatment. Brain connectivity will be measured using functional magnetic resonance imaging;
- The proportion of adolescents with subthreshold emotional disorders at the end of 18 months of treatment;
Study flow chart is shown in [Figure 1].
Schedule of outcome measures is shown in [Table 2].
We assumed 80% power to detect a significant improvement of effect size of 0.4 in PHQ scores, with a two-sided significant level of 0.05. To this end, a sample size of 198 will be needed. A dropout rate of approximately 10% is anticipated and then 224 participants will be recruited.
First, the participants will be numbered according to the order of enrollment, starting with a random number selected from the random number table. Participants who are assigned an odd number will be included in the trial group, and those who are assigned an even number will be included in the control group.
Because of obvious differences in the treatment methods received by the subjects, only outcome evaluators will be blinded to the study protocol.
This study will be performed in strict accordance with the regulations of Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Guizhou Brain Hospital (Guangzhou Huiai Hospital) on October 26, 2016 (approval No. 2016-048) [Additional file 1] [Additional file 1]. This study was registered with ClinicalTrials.gov (identifier: NCT03300778) on October 3, 2017. Protocol version: 1.0. Before participant enrollment, the investigators should completely and comprehensively introduce the objectives, procedures, possible benefits and risks of the study to the participants’ legal guardians. A written informed consent will be obtained from the participants’ legal guardians [Additional file 2] [Additional file 2]. The subjects and their legal guardians will know that they have the right to withdraw from the study at any time. Written informed consent will be kept as clinical research document for future use. Personal privacy and data confidentiality will be protected during the study. Writing and editing of the manuscript will be performed in accordance with the statement of Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) [Additional file 3] [Additional file 3].
According to the intention-to-treat principle, all subjects who receive one intervention and complete the baseline evaluation will be included in the final analysis. For patients who drop out of the study before it ends, their last observed data will be used for all subsequent observation times, i.e., last observation carried forward will be used for imputing missing data. SPSS 23.0 software (IBM Corp., Armonk, NY, USA) will be used for statistical analysis. Measurement data will be compared between groups using the parameter or non-parametric test according to data distribution. Count data will be compared between groups using chi-square test or Fisher exact probability test. A level of P < 0.05 will be considered statistically significant.
Data collection and management
All data will be recorded in case report forms by trained personnel and recorded in electronic database immediately. To ensure the accuracy and reliability of the data, the study monitor will verify and cross check the case report forms based on the investigator’s original documentation. Missing information or specific errors in the data will be detected by the program and the results will be sent to the investigator for resolution. After study completion, the original case report forms will be kept in the researcher center for 5 years.
Data quality control
The clinical research associate will be responsible for quality control and supervision of the study in terms of data collection and analysis, investigator training, subject compliance, and study conduction to ensure that the investigators strictly follow the study protocol, relevant standard operating procedure, guiding principle and regulation requirement in the study process.
During the research process, clinical research associate should visit the research site regularly to know the research process and the compliance of investigators with the study protocol, process, applicable laws and regulations to ensure that the data obtained is objective, true and legal. At the end of the study, clinical research associate should check all documents and archive them.
Modification of study protocol
After discussed and confirmed by investigators and approved by the institute ethics committee, the study protocol will not be altered. However, if new information has been obtained or relevant institutes require changing the contents of the study protocol, approval by institute ethics committee should be obtained again.
The inspection committee will be composed of those who do not participate in the trial to check whether trial imple-mentation, data recording and analysis will be in conformity with the requirements of the study protocol and applicable laws and regulations. The inspection report should be attached to the application materials submitted to the management authority. Inspection will be performed once every other 2 months. Trial progression will be reported to institute ethics committee and trial status will be updated in the registration database.
The name of each subject will be kept strictly confidential. Investigators should report the results in scientific research conference, academic journals and various government agencies. Subject’s name will not be mentioned in these reports.
| Discussion|| |
A 12-week exercise intervention is relatively short, and future study would evaluate longer-time intervention.
An investigation of the effects of aerobic exercise on adolescents with subthreshold mood symptoms will provide new perspective regarding the treatment of these conditions.
A large number of studies have confirmed that aerobic exercise can promote sympathetic nerve stimulation, increase the level of blood adrenaline, improve mood, and significantly improve negative emotions such as anxiety, mania, and depression (Konopka and Harber, 2014; Yang et al., 2015a; Young et al., 2015; de Oliveira et al., 2017; Hashida et al., 2017; LeBouthillier and Asmundson, 2017; MacIntosh et al., 2017; Miele and Headley, 2017; Moreau et al., 2017; Pagonas et al., 2017; Turner et al., 2017). However, no large-sample-sized clinical studies have examined whether aerobic exercise can improve symptoms in adolescents with subthreshold mood symptoms and cognition in clinically-well adolescents. Exercise is likely to be more acceptable by children and adolescent patients compared with other treatments such as medication.
Study status: Data analysis is ongoing.
Date of registration: October 3, 2017.
Anticipated recruitment duration: November 2017 to July 2018.
Anticipated study completion: December 2020.
Additional file 1: Hospital ethics approval (Chinese).
Additional file 2: Informed consent template (Chinese).
Additional file 3: SPIRIT checklist.
Study concept and design: KL; study details and manuscript writing: GYX, KL. Both authors approved the final version of this manuscript for publication.
Conflicts of interest
The authors have no conflicts of interest to declare.
This study is financially supported by the National Key Special Subproject of “Research on Prevention and Control of Major Chronic Non-infectious Disease” (No. 2016YFC1306702; to GYX).
Institutional review board statement
The study protocol was approved by the Institutional Review Board of Guizhou Brain Hospital (Guangzhou Huiai Hospital) on October 26, 2016 (approval No. 2016-048). This study will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association.
Declaration of participant consent
The authors certify that they will obtain all appropriate consent forms from the legal guardians of participants. In the forms, the legal guardians will give their consent for participants’ images and other clinical information to be reported in the journal. The legal guardians understand that the participants’ names and initials will not be published and due efforts will be made to conceal their identity.
This study followed the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement.
The statistical methods of this study were reviewed by the biostatistician of Guangzhou Psychiatric Hospital, China.
Copyright license agreement
The Copyright License Agreement has been signed by both authors before publication.
Data sharing statement
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). Data will be available immediately following publication, with no end date. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Anonymized trial data will be available indefinitely at www.figshare.com.
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Externally peer reviewed.
Open access statement
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribu-tion-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
P-Reviewers: Wu HS, Zhang XY; C-Editor: Zhao M; S-Editors: Yu J, Li CH; L-Editors: Song LP, Wang L; T-Editor: Jia Y
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[Table 1], [Table 2]