Subthreshold DepressionNCT04816617
The Effect of Exercise on Cognition and Preventing Depression in Young People
A study testing Aerobic exercise intervention and Psycho-education in people with Subthreshold Depression and Exercise, run by Guangzhou Psychiatric Hospital at 1 site in China.
Trial summary
It is estimated that approximately 30% of child and adolescents manifest subthreshold depression (including other specified depressive disorder and unspecified depressive disorder), which can further develop into major depression with as high as 25%-50% within one year. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Subthreshold Depression, Exercise, Clinically-well
- What is being tested?
- Aerobic exercise intervention and Psycho-education
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 628 participants
- Where
- 1 siteChina
- Study dates
- 21 Oct 2021to 31 Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- PHQ-9 ≥5
- 12~17 years old.
Who cannot join
- Current or past DSM-5 criteria for major depressive disorder,Bipolar disorder, Schizophrenia.
- Musculoskeletal problems such as arthritis, gout, osteoporosis, or back, hip or knee pain that may interfere with exercising
- A history of organic brain disease or brain trauma
- Alcohol, drug or other psychoactive substance abuse or dependence
- Currently enrolled in another exercise study
- Any conditions that would make exercise unsafe or unwise
- Taking medication that interferes with heart rate response to exercise such as beta blockers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A 12-month，Parallel-group, Randomised Controlled Exercise Trial in Young People With and Without Subthreshold Depression
It is estimated that approximately 30% of child and adolescents manifest subthreshold depression (including other specified depressive disorder and unspecified depressive disorder), which can further develop into major depression with as high as 25%-50% within one year. The cognitive development of adolescents is a critical area of research, given its significant implications for academic performance, mental health, and overall well-being. During adolescence, the brain undergoes substantial structural and functional changes, particularly in regions associated with executive function, memory, and processing speed. These changes provide a unique opportunity to explore interventions that can support and enhance cognitive development. One such promising intervention is physical exercise. Adolescence is characterized by rapid cognitive growth, including improvements in executive functions such as planning, decision-making, and inhibitory control. These cognitive abilities are essential for academic success and social interactions. However, this period also presents risks for cognitive and emotional disturbances, making it vital to identify effective strategies to promote healthy cognitive development. Despite the promising evidence, there is a need for more rigorous research, particularly long-term randomized controlled trials (RCTs), to establish the causal relationship between exercise and cognitive function in adolescents, including those with sub-threshold depression. Most existing studies have focused on short-term interventions or specific cognitive tasks, leaving a gap in our understanding of the sustained effects of exercise over an extended period. Additionally, the transition from supervised to unsupervised exercise and its impact on adherence and cognitive outcomes is underexplored. There is also a need to evaluate the potential of exercise as a preventive strategy against the development of major depressive disorder in this vulnerable population. Additionally, evidence suggests that participants with lower baseline levels of physical activity may experience more significant cognitive improvements from exercise interventions than those with higher baseline activity levels. This highlights the importance of considering baseline physical activity levels when assessing the effectiveness of exercise on cognitive outcomes.
This study will particularly focus on the cognitive domains of attention, memory, and processing speed. These domains are critical for academic success and daily functioning and are often impacted in adolescents with sub-threshold depression. Previous research has shown that these domains are particularly responsive to physical exercise interventions.
Read the detailed description
This is multi-center, psycho-education randomized controlled trial, consisting of two periods with each of 6 months (i.e supervised and maintenance period). In the exercise intervention arm, during the first 6 months, participants will be asked to do moderate-intensity aerobic exercise 3-4 times a week, which will be supervised in person by physical educators/professionals. In the next 6-month maintenance period, participants will be asked to continue doing aerobic exercise at the same intensity and frequency, which will not be supervised in person by educators/professionals, but they will be sent reminders and report adherence monthly. All of the physical activity will be recorded by accelerometer at scheduled time points (e.g. the first week, 6 week, 3 month, 6 month, 9 month, 12 month). Psycho-education group will be given 6 sections of general psycho-education onsite and/or virtually dependent on the surroundings with regards to the impact of the COVID-19 pandemic. The main aim of this trial is to investigate the effect of long-term aerobic exercise on cognition and prevention depression in young people with or without subthreshold depression.
- Conditions
- Subthreshold Depression, Exercise, Clinically-well, Cognitive Change
- Being tested
- Aerobic exercise intervention, Psycho-education
- Keywords
- Subthreshold depression, aerobic exercise, Major depression, Intervention; Cognition
- Medical subject headings
- Motor Activity, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic exercise interventionBehavioural
The whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc.
Psycho-educationBehavioural
It consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months.
| Study group | Role | What they receive |
|---|---|---|
| Aerobic Exercise | Experimental | The whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc. Receives: Behavioral: Aerobic exercise intervention |
| Psycho-education | Placebo comparator | It consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months. Receives: Behavioral: Psycho-education |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in Attention measure by Choice Reaction Time task (CRT) incorporated into THINC-it®
Attention will be measured by the Choice Reaction Time task (CRT).
Measured: month 12
Secondary outcomes (11)
The rate of occurrence of MDD
Kiddie-Sads-Present and Lifetime Version (K-SADS-PL)
Measured: Month 6 and month 12
Levels of inflammatory biomarkers from baseline
inflammatory biomarkers (IL-6, CRP etc) will be analyzed using ELISA
Measured: Month 6 and month 12
Occurrence of Non-suicidal self-injury and suicidal behavior
Measured: Month 6 and month 12
Physical activity level
The International Physical Activity Questionnaire - Short Form (IPAQ - SF) will be used to assess physical activity level
Measured: Month 6 and 12
P Wave changes over time
Brain activity will be detected by Electroencephalograph (EEG)
Measured: Month 6 and 12
New onset of subthreshold depression in healthy volunteers
subthreshold depression is defined by DSM-5 Other specified Depressive Disorder and Unspecified Depressive Disorder
Measured: Month 6 and 12
Changes from baseline in memory measured N-back memory task (N-BACK)
N-back memory task (N-BACK) was used to measure short-term memory.
Measured: month 6 and month 12
Changes from baseline in subjective cognition measured by Perceived Deficits Questionnaire 5 (PDQ-5)
Perceived Deficits Questionnaire 5 (PDQ-5) is a subjective measure, which broadly evaluates attention/concentration, planning/organisation, as well as retrospective and prospective memory.
Measured: Month 6 and 12
Changes from baseline in Processing Speed.
Digit Symbol Substitution Test (DSST) was used to measure Processing Speed.
Measured: Month 6 and 12
Changes from baseline in executive function.
Trail Making Test-B (TMT-B) was used to measure Executive function.
Measured: Month 6 and 12
Changes from baseline in Attention measure by Choice Reaction Time task (CRT)
Attention measure by Choice Reaction Time task (CRT)
Measured: month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start21 Oct 2021
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Subthreshold DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 628 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guangzhou Psychiatric Hospital
- Sponsor type
- Other government
- Collaborators
- Shanghai Mental Health Center
- Responsible party
- Principal investigator, Kangguang Lin, Guangzhou Psychiatric Hospital
- Investigators
- Kangguang Lin, MD,PhD, Study director, The Affiliated Brain Hospital of Guangzhou Medical UniversityTifei Yuan, PhD, Principal investigator, Shanghai Mental Health CenterKwok-Fai So, PhD, Study chair, Jinan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04816617
- Sponsor's protocol ID
- Exercise, Cogntion and MDD
- Status last verified
- Aug 2024
- First submitted
- 23 Mar 2021
- Last updated
- 28 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Yan X, Shao R, Jin J, Lu W, Jiang Z, Zhang G, Zhang Q, Li X, Tian X, Stubbs B, Vancampfort D, Solmi M, Fornaro M, Carvalho AF, Yau SS, Cong F, So KF, Lin K. Aerobic Exercise and Subthreshold Depressive Symptoms in Adolescents: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Jul 1;9(7):e2621568. doi: 10.1001/jamanetworkopen.2026.21568.
PubMed 42406403Werneck AO, Tian X, Lu W, Li D, Liu T, Wu S, Li X, Wang R, Gao Y, Li X, Chen J, Vancampfort D, Solmi M, Fabiano N, Schuch F, Plener PL, McIntyre RS, So KF, Stubbs B, Lin K. Can exercise reduce the risk of suicidal ideation and behaviors in youth at school? A 12-month cluster randomized control trial. J Psychiatr Res. 2026 Mar;194:71-78. doi: 10.1016/j.jpsychires.2025.12.025. Epub 2025 Dec 11.
PubMed 41448028
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-month，Parallel-group, Randomised Controlled Exercise Trial in Young People With and Without Subthreshold Depression
- ClinicalTrials.gov ID
- NCT04816617
- Acronym / sponsor ID
- Exercise, Cogntion and MDD
- Conditions
- Subthreshold Depression, Exercise, Clinically-well, Cognitive Change
- Keywords
- Subthreshold depression, aerobic exercise, Major depression, Intervention; Cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 628 participants (actual)
- Lead sponsor
- Guangzhou Psychiatric HospitalOther government
- Collaborators
- Shanghai Mental Health Center
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 25 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is estimated that approximately 30% of child and adolescents manifest subthreshold depression (including other specified depressive disorder and unspecified depressive disorder), which can further develop into major depression with as high as 25%-50% within one year. The cognitive development of adolescents is a critical area of research, given its significant implications for academic performance, mental health, and overall well-being. During adolescence, the brain undergoes substantial structural and functional changes, particularly in regions associated with executive function, memory, and processing speed. These changes provide a unique opportunity to explore interventions that can support and enhance cognitive development. One such promising intervention is physical exercise. Adolescence is characterized by rapid cognitive growth, including improvements in executive functions such as planning, decision-making, and inhibitory control. These cognitive abilities are essential for academic success and social interactions. However, this period also presents risks for cognitive and emotional disturbances, making it vital to identify effective strategies to promote healthy cognitive development. Despite the promising evidence, there is a need for more rigorous research, particularly long-term randomized controlled trials (RCTs), to establish the causal relationship between exercise and cognitive function in adolescents, including those with sub-threshold depression. Most existing studies have focused on short-term interventions or specific cognitive tasks, leaving a gap in our understanding of the sustained effects of exercise over an extended period. Additionally, the transition from supervised to unsupervised exercise and its impact on adherence and cognitive outcomes is underexplored. There is also a need to evaluate the potential of exercise as a preventive strategy against the development of major depressive disorder in this vulnerable population. Additionally, evidence suggests that participants with lower baseline levels of physical activity may experience more significant cognitive improvements from exercise interventions than those with higher baseline activity levels. This highlights the importance of considering baseline physical activity levels when assessing the effectiveness of exercise on cognitive outcomes.
This study will particularly focus on the cognitive domains of attention, memory, and processing speed. These domains are critical for academic success and daily functioning and are often impacted in adolescents with sub-threshold depression. Previous research has shown that these domains are particularly responsive to physical exercise interventions.
Detailed description
This is multi-center, psycho-education randomized controlled trial, consisting of two periods with each of 6 months (i.e supervised and maintenance period). In the exercise intervention arm, during the first 6 months, participants will be asked to do moderate-intensity aerobic exercise 3-4 times a week, which will be supervised in person by physical educators/professionals. In the next 6-month maintenance period, participants will be asked to continue doing aerobic exercise at the same intensity and frequency, which will not be supervised in person by educators/professionals, but they will be sent reminders and report adherence monthly. All of the physical activity will be recorded by accelerometer at scheduled time points (e.g. the first week, 6 week, 3 month, 6 month, 9 month, 12 month). Psycho-education group will be given 6 sections of general psycho-education onsite and/or virtually dependent on the surroundings with regards to the impact of the COVID-19 pandemic. The main aim of this trial is to investigate the effect of long-term aerobic exercise on cognition and prevention depression in young people with or without subthreshold depression.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aerobic Exercise | Experimental | Behavioral: Aerobic exercise interventionThe whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc. |
| Psycho-education | Placebo comparator | Behavioral: Psycho-educationIt consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months. |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- PHQ-9 ≥5
- 12~17 years old.
Key exclusion criteria (7 listed)
- Current or past DSM-5 criteria for major depressive disorder,Bipolar disorder, Schizophrenia.
- Musculoskeletal problems such as arthritis, gout, osteoporosis, or back, hip or knee pain that may interfere with exercising
- A history of organic brain disease or brain trauma
- Alcohol, drug or other psychoactive substance abuse or dependence
- Currently enrolled in another exercise study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic exercise interventionThe whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc. | Behavioural | Aerobic Exercise |
| Psycho-educationIt consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months. | Behavioural | Psycho-education |
Primary outcome
Changes from baseline in Attention measure by Choice Reaction Time task (CRT) incorporated into THINC-it®
Time frame: month 12
Attention will be measured by the Choice Reaction Time task (CRT).
11 secondary outcomes
The rate of occurrence of MDD
Time frame: Month 6 and month 12
Levels of inflammatory biomarkers from baseline
Time frame: Month 6 and month 12
Occurrence of Non-suicidal self-injury and suicidal behavior
Time frame: Month 6 and month 12
Physical activity level
Time frame: Month 6 and 12
P Wave changes over time
Time frame: Month 6 and 12
New onset of subthreshold depression in healthy volunteers
Time frame: Month 6 and 12
Changes from baseline in memory measured N-back memory task (N-BACK)
Time frame: month 6 and month 12
Changes from baseline in subjective cognition measured by Perceived Deficits Questionnaire 5 (PDQ-5)
Time frame: Month 6 and 12
Changes from baseline in Processing Speed.
Time frame: Month 6 and 12
Changes from baseline in executive function.
Time frame: Month 6 and 12
Changes from baseline in Attention measure by Choice Reaction Time task (CRT)
Time frame: month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Derived from this study: PubMed 42406403Yan X, Shao R, Jin J, Lu W, Jiang Z, Zhang G, Zhang Q, Li X, Tian X, Stubbs B, Vancampfort D, Solmi M, Fornaro M, Carvalho AF, Yau SS, Cong F, So KF, Lin K. Aerobic Exercise and Subthreshold Depressive Symptoms in Adolescents: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Jul 1;9(7):e2621568. doi: 10.1001/jamanetworkopen.2026.21568.
- Derived from this study: PubMed 41448028Werneck AO, Tian X, Lu W, Li D, Liu T, Wu S, Li X, Wang R, Gao Y, Li X, Chen J, Vancampfort D, Solmi M, Fabiano N, Schuch F, Plener PL, McIntyre RS, So KF, Stubbs B, Lin K. Can exercise reduce the risk of suicidal ideation and behaviors in youth at school? A 12-month cluster randomized control trial. J Psychiatr Res. 2026 Mar;194:71-78. doi: 10.1016/j.jpsychires.2025.12.025. Epub 2025 Dec 11.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kangguang Lin, MD,PhD study director
The Affiliated Brain Hospital of Guangzhou Medical University
Tifei Yuan, PhD principal investigator
Shanghai Mental Health Center
Kwok-Fai So, PhD study chair
Jinan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic exercise intervention and Psycho-education in people with Subthreshold Depression and Exercise, run by Guangzhou Psychiatric Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline in Attention measure by Choice Reaction Time task (CRT) incorporated into THINC-it® (time frame: month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04816617, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.