Efficacy of Bright Light Therapy on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms: Protocol for a Randomised Controlled Trial

This study aims to validate the therapeutic efficacy and safety of bright light therapy (BLT) in ameliorating cognitive impairment (CI) in major depressive disorder (MDD), characterize the functional and structural features of the hippocampus (HPC)-dorsolateral prefrontal cortex (dlPFC) neural circuitry in MDD participants with CI and examine the mediating effect of the HPC-dlPFC neural circuit on CI induced by BLT treatment in MDD participants. MDD participants will be required to only receive selective serotonin reuptake inhibitors (SSRIs) as monotherapy for at least four weeks, or medication-free status before enrollment. Eligible participants will be randomly assigned to the experimental group and the control group. The experimental group will receive the intervention of BLT, and the control group will receive the intervention of dim red light (DRL). The intervention will last for four weeks, 6 days per week, with 40 minutes each day between 7 am and 10 am. The MDD participants will be followed once in the end of each week during the 4-week intervention and in the end of the 4th week after intervention. Demographic information will be collected at baseline; cognitive function will be evaluated at baseline, weeks 2, 4, and 8 after intervention beginning; and other symptoms such as depression, anxiety and sleep were assessed at baseline, weeks 1, 2, 3, 4, and 8 after intervention beginning. Moreover, structural and functional MRI scans will be made at baseline and post-intervention. During the intervention, MDD participants will be required to keep a record of daily light exposure duration and complete the daily sleep diary as well.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Major Depressive Disorder (MDD); Neuroimaging; Bright Light Treatment
• Intervention / Treatment: Device: DRL; Device: BLT

Detailed Description

This study is mainly designed as a randomized controlled study. It focuses on CI in MDD participants, with an experimental group and a control group established. MDD participants will be required to only receive selective serotonin reuptake inhibitors (SSRIs) as monotherapy for at least four weeks, or medication-free status before enrollment. The medication dosage need to maintain unchanged throughout the entire intervention. The experimental group received the intervention of BLT, and the control group additionally received the intervention of dim red light (DRL). The intervention lasts for four weeks (six days per week, with 40 min per day between 7am and 10 am). Follow-up will be conducted once at the 4th weekends after intervention. Cognitive appraisal will be conducted using a composite battery derived from the Chinese version of Measurement Consensus Cognitive Battery (MCCB), the Chinese Biref Cognitive Test(C-BCT), and Perceived Deficits Questionnaire(PDQ)at baseline, weeks 2, 4 and 8 after intervention beginning. Other clinical symptoms will be assessed by The 17-item Hamilton Depression Rating Scale (HAMD-17), the 16-item Quick Self Rating Depression Symptoms Scale (QIDS), Hamilton Anxiety Rating Scale (HAMA), the 7-item Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh sleep quality index (PSQI), Insomnia Severity Index (ISI), Chinese version of the Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire(Q-LES-Q-SF) and Sheehan Disability Scale(SDS) at baseline, weeks 1, 2, 3, 4 and 8 after intervention beginning. At the same time, the Safety and Applicability of the intervention during the treatment process will be investigated using Young Mania Rating Scale (YMRS), the Side Effects Rating Scale for Serotonin Specific Reuptake Inhibitors (SERS) and a self-made scale.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaozhen Lv, Ph.D; Phone Number: +8601062723705; Email: lxz120300@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100191
      • Recruiting
      • Peking University Sixth Hospital
      • Contact: Xiaozhen Lv, Ph.D; Phone Number: +8601062723705; Email: lxz120300@163.com
  • Shanxi
    • Yanan, Shanxi, China
      • Recruiting
      • Yan'an Third People's Hospital
      • Contact: Jun Yuan; Email: 337559650@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

The inclusion and exclusion criteria for MDD patients. 1、Inclusion Criteria:

1. MDD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-Ⅳ), first episode or recurrence, confirmed by an experienced psychiatrist using the Mini International Neuropsychiatric Interview.
2. Age between 18 and 60 years; and gender no-limited;
3. The severity of MDD symptoms must be ≥14 scores on the HAMD-17;
4. With CI currently, defined as a total score of <70 on the SC;
5. A SSRI monotherapy at stable dosages for at least 4 weeks; or medication-free status;
6. Education level above primary school, able to understand and cooperate in completing the study procedures;
7. Voluntarily participating in this study and sign the informed consent before enrollment.

2、Exclusion Criteria:

1. Current or past diagnosis of any disorder other than MDD according to DSM-Ⅳ criteria;
2. The scores on the Young Mania Rating Scale (YMRS) are>8;
3. The participants who have undergone other intervention in addition to SSRIs whinin the past 6 months or now, or who plan to do that in 1 month;
4. The participants with strong self-blame, self-harm, or suicidal risks (the HAMD-17 suicide item score of ≥3);
5. The participants with severe physical illnesses, including heart failure, renal failure, severe liver dysfunction, hyperthyroidism, or hypothyroidism; Or a history of severe brain trauma or organic brain pathology (e.g., intracerebral hemorrhage, large-area cerebral infarction, encephalitis, epilepsy), as well as neurological diseases;
6. The participants with any degree of retinal pathology, including retinal dystrophy, age-related macular degeneration, diabetic retinopathy, cataracts, glaucoma, or other ocular diseases;
7. The participants with photosensitive conditions, such as systemic lupus erythematosus, porphyria, chronic photodermatitis, solar urticaria, or those currently receiving medications that may increase photosensitivity (e.g., phenothiazines, antimalarials, propranolol, hypericin, stimulants, or chronic treatment with nonsteroidal anti-inflammatory drugs);
8. Pregnant or lactating women;
9. The participants with contraindications to MRI, such as the presence of non-MRI-safe metallic implants or claustrophobia;
10. The participants deem unsuitable for inclusion in this study by the investigator for other reasons.

Withdrawal and Termination Criteria：

1. The participants meet one of the exclusion criteria above after enrollment;
2. When the participants' treatment regimen need change;
3. The participants who fail to cooperate or voluntarily withdraw from the study;
4. Due to severe adverse events, the patients are unable to tolerate phototherapy;
5. The participants who fail to adhere to the study protocol intervention for three consecutive days or for a cumulative duration exceeding seven days;
6. Cancellation of the study.

The inclusion and exclusion criteria for Health controls

1. Inclusion criteria

1. Age between 18 and 60 years; and gender no-limited;
2. Without CI currently, defined as a total score of ≤ 70 on the SC;
3. Education level above primary school, able to understand and cooperate in completing the study procedures;
4. Voluntarily participating in this study and sign the informed consent before enrollment.

2.Exclusion criteria

1. Current or past diagnosis of any psychiatric disorders, or history of substance/drug abuse or dependence;
2. Current or past diagnosis of severe somatic diseases, such as heart failure, renal failure, severe liver dysfunction, or hyperthyroidism/hypothyroidism;
3. History of severe traumatic brain injury or organic brain lesions;
4. Pregnant or lactating women;
5. The participants with contraindications to MRI, such as the presence of non-MRI-safe metallic implants or claustrophobia.
6. The participants deem unsuitable for inclusion in this study by the investigator for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: healthy control
Placebo Comparator: DRL control group; Eligible MDD participants will be randomly subjected to the DRL control group. The light source intensity will be set at <100 lux and placed 0.6 meters away from the MDD participant. They will be required to staring at the light source for 2 seconds every 5 minutes. The DRL control group will be administered for 40 minutes each day between 7:00 AM and 10:00 AM, lasting for four weeks, 6 days per week.	Device: DRL; Using a dim red light box as the placebo, with an intensity of <100lux and a main wavelength of 690.4nm
Experimental: BLT experimental group; Eligible MDD participants will be randomly subjected to the BLT experimental group. The source intensity of BLT experimental group will be set at 10000 lux and placed 0.45 meters away from the MDD participant. They will be required to staring at the light source for 2 seconds every 5 minutes. The BLT experimental group will be administered for 40 minutes each day between 7:00 AM and 10:00 AM, lasting for 4 weeks, 6 days per week.	Device: BLT; Using a hybrid white light box with independent intellectual property rights, with an intensity of 10000lux and a main wavelength of 476.4nm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symbol Coding (SC)	The Symbol Coding (SC) is a coding paradigm adapted from the Digit Symbol Substitution Test (DSST), both of which use essentially the same method, except in reverse; instead of drawing symbols that match digits, the SC requires to write the matching digit in the blank. The task has been included as a subtest in the Brief Assessment of Cognition in Schizophrenia; in this task, subjects are required to write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 s, as based on a key provided to them, with higher scores reflecting better performance.	screen, baseline, weeks2, 4, and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale-17（HDRS-17）	The Hamilton Depression Rating Scale-17 (HAMD-17), developed by Hamilton in 1960, is a widely used clinical rating scale consisting of 17 items that evaluate various depressive symptoms, including mood, suicidal thoughts, sleep disturbances, loss of interest, psychomotor changes, anxiety, gastrointestinal and somatic symptoms, sexual dysfunction, and weight loss. Scored on a scale of 0 to 4 (with some items possibly using a 0 to 2 scale), the total score reflects the severity of depressive symptoms and is used for diagnosing depression, planning tailored treatment, monitoring treatment effectiveness, and conducting research on depression treatment efficacy.	screen, baseline, weeks1, 2, 3, 4, and 8
The 20-item Perceived Deficits Questionnaire for Depression（PDQ-D-20）	The Chinese version of the Perceived Deficits Questionnaire for Depression (PDQ-D) has been validated for reliability and validity among patients with depression in China. The PDQ-D comprises 20 items, yielding a total score that ranges from 0 to 80. Higher scores indicate a greater severity of self-perceived cognitive symptoms. Demonstrating good reliability and validity, the questionnaire assesses patients' cognitive function across four dimensions: attention/concentration, prospective memory, retrospective memory, and planning and organization.	baseline, weeks 2, 4, and 8
The Chinese Brief Cognitive Test（CBCT）	Cognitive function will be also assessed using the CBCT, which has been validated in a large-scale study of schizophrenia patients and has shown good internal consistency and test-retest reliability. Also, additional studies in MDD population provide further evidence of its reliability and validity supporting the robustness of this scale for assessing cognitive function in these clinical groups.	baseline, weeks 2, 4, and 8
Stroop Color-Word Test (SCWT)	The Stroop Color Word Test (SCWT) was developed by Professor Stroop in 1935 to evaluate subjects' executive functions. The test is a measure of selective attention and the degree of inhibition of irrelevant information in executive functioning. It consists of three main parts: reading words (Stroop-w), color naming (Stroop-c), and color-word interference (Stroop-cw), which require subjects to accurately and quickly read the words or the colors, respectively, as required.	baseline, weeks 2, 4, and 8
Hopkins Verbal Learning Test-Revised (HVLT-R)	Hopkins Verbal Learning Test-Revised (HVLT-R) is a widely used neuropsychological assessment tool designed to evaluate verbal memory and cognitive function. Developed by J. Brandt and Benedict in 2001, the HVLT-R consists of a list of 12 nouns divided into three semantic categories (e.g., dwelling places, four-legged animals, and precious stones), with four words per category. The assessment involves three learning trials, where participants are presented with the list of words and are asked to recall as many words as possible immediately after each presentation. Additionally, there is a delayed recall trial, where participants are asked to recall the words after a delay of 20-25 minutes. The scoring principle is based on the number of correctly recalled words during each learning trial and the delayed recall trial. The total score for the three learning trials and the delayed recall trial is calculated as well.	baseline, weeks 2, 4, and 8
Generalized Anxiety Disorder-7（GAD-7）	The Generalized Anxiety Disorder-7 is a standardized assessment tool developed by Spitzer et al. in 2006. It is a 7-item questionnaire designed to evaluate the severity of anxiety symptoms over the past two weeks. The scale covers various aspects of anxiety, including feelings of tension, worry, irritability, and difficulty relaxing. Each item is rated on a 4-point scale, ranging from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 to 21. Higher scores indicate more severe anxiety symptoms. The GAD-7 is primarily used as a screening and assessment tool in clinical and research settings, aiding clinicians in identifying and quantifying anxiety symptoms, monitoring changes over time, and evaluating treatment effectiveness. It is a simple, reliable, and valid instrument that can be easily administered and scored, making it a valuable addition to the clinical assessment of anxiety disorders.	baseline, weeks1, 2, 3, 4, and 8
Quick Inventory of Depressive Symptomatology-Self-Report（QIDS-SR-16）	The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16), a rigorous and systematic self-assessment scale developed by Rush et al. in 2003 with subsequent refinements, is a widely recognized tool for quickly gauging depressive symptoms over the past week. It comprises 16 items covering various dimensions of depression, including mood, sleep, appetite, energy levels, concentration, self-esteem, suicidal ideation, and daily functioning, each rated on a 4-point scale (0-3). The scale assesses the severity and frequency of symptoms, with higher scores indicating more severe depression. The QIDS-SR16 serves multiple purposes: it aids in screening and assessing depressive symptoms in clinical settings, allows individuals to monitor their depressive state over time, serves as a research tool in clinical studies evaluating treatment effectiveness, and provides valuable information that can support the diagnostic process when combined with clinical interviews.	baseline, weeks1, 2, 3, 4, and 8
Pittsburgh Sleep Quality Inventory（PSQI）	The PSQI, or Pittsburgh Sleep Quality Inventory, was developed by Buysse et al. in 1989. It is a widely used and standardized self-report questionnaire designed to assess sleep quality over the past month. The PSQI consists of 19 self-rated items and 5 additional items for bed partner or roommate ratings (though only 18 of the self-rated items are scored). The assessment covers seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component is scored on a 0-to-3 scale, with the total PSQI score ranging from 0 to 21. Higher scores indicate poorer sleep quality, with a total score of 5 or less indicating good sleep quality, 6-10 indicating fair sleep quality, 11-15 indicating poor sleep quality, and 16 or more indicating very poor sleep quality. The PSQI serves multiple purposes, including clinical diagnosis of sleep disorders, research on sleep quality, and eval	baseline, weeks1, 2, 3, 4, and 8
Young Mania Rating Scale（YMRS）	The Young Mania Rating Scale (YMRS), developed by R.C. Young and colleagues in 1978, is a clinician-administered rating scale designed to assess the severity of manic symptoms over the past week. It comprises 11 items that evaluate various aspects of mania, including elevated mood, increased activity and energy, sexual interest, sleep pattern, irritability, speech, language-thought disorders, content of thought, aggressive or destructive behavior, appearance, and insight. The scoring system varies across items, with some rated on a 0-4 scale and others on a 0-8 scale. The total score is obtained by summing the ratings of all items, providing a quantitative measure of manic severity. Higher scores indicate more severe manic symptoms. The YMRS is primarily used in clinical and research settings for the assessment of manic states.	screen, baseline, weeks1, 2, 3, 4, and 8
Asberg Side-Effect Rating Scale for Antidepressants (SERS)	Asberg Side-Effect Rating Scale for Antidepressants (SERS) is a rating scale developed by Swedish psychiatrist M. Asberg in 1970. It is specifically designed to evaluate the adverse effects experienced by individuals following the administration of antidepressant medications. The scale contains 14 items that assess a wide range of symptoms, including physical fatigue, dizziness, headache, sleep disturbance, orthostatic hypotension, palpitations, tremors, sweating, dry mouth, constipation, urinary difficulties, somnolence, sexual dysfunction, and other symptoms. Each item is rated on a 4-point scale ranging from 0 (absent) to 3 (severe), allowing for a comprehensive quantification of the severity of side effects. The total score, calculated by summing the ratings of all items, provides an overall measure of antidepressant-related adverse effects. The SERS is primarily used in clinical and research settings to aid in the identification, monitoring, and documentation of side effects.	baseline, weeks1, 2, 3, 4, and 8
Quality of Life Enjoyment and Satisfaction Questionnaire,Short Form（Q-LES-Q-SF）	The Q-LES-Q-SF, developed by Endicott et al. in 1995, consists of 16 items that assess an individual's subjective satisfaction with their quality of life over the past 7 days. The first 14 items reflect various aspects of quality of life, including physical and mental health, mood, work, household responsibilities, social relationships, family relationships, leisure activities, daily living skills, sexual functioning, financial status, living environment, mobility, hobbies, and overall subjective satisfaction with physical and mental health. Items 15 and 16 assess daily medical care and overall life satisfaction. Each item is rated on a scale from 1 to 5, with higher scores indicating better quality of life. The overall score for the Q-LES-Q-SF is derived from the sum of the scores from items 1 to 14.	baseline, weeks1, 2, 3, 4, and 8
Sheehan disability scale (SDS)	The SDS evaluates the impact of depression on a patient's work, social life, and family responsibilities. The total score ranges from 0 to 30, with higher scores indicating greater functional impairment . The SDS has demonstrated strong reliability and validity in depressed populations.	baseline, weeks1, 2, 3, 4, and 8
Hamilton Anxiety Scale (HAMA）	Originally developed by Hamilton in 1959, the HAMA is a classic clinician-administered questionnaire assessing both somatic and psychic anxiety severity. The 14-item instrument captures psychic anxiety (items 1-6, 14) and somatic anxiety (items 7-13). Each item is rated on a 5-point Likert scale from 0 (absent) to 4 (very severe), with higher total scores indicating more severe clinical anxiety. The construct validity and reliability of the Chinese HAMA adaptation have been rigorously established in domestic psychometric studies.	Baseline, week 1, 2, 3, 4 and 8
Insomnia Severity Index (ISI）	The Insomnia Severity Index (ISI) is a standardized tool used to assess the severity of insomnia symptoms and their impact on daily life. It consists of 7 items that encompass difficulties in falling asleep, sleep maintenance, early awakening, satisfaction with sleep, distress caused by symptoms, impairment of daily functioning, and concern about insomnia. Each item is rated on a scale from 0 to 4, with a total score ranging from 0 to 28. A higher score indicates more severe insomnia issues.	Baseline, week 1, 2, 3, 4 and 8
Color Trails Test （CTT）	The Color Trails Test (CTT) (Maj, D'Elia, Satz, Janssen, Zaudig, Uchiyama et al., 1993; D'Elia, Satz, Uchiyama & White, 1996) is a language-free version of the Trail Making Test (TMT) that was developed to allow for broader cross-cultural application to measure sustained attention and divided attention in adults.The CTT is comprised of two tasks: CTT-1 must be administered first and requires the respondent to connect circles in an ascending numbered sequence (1-25). CTT-2 must follow the CTT1 and requires the respondent to connect numbers in an ascending sequence while alternating between pink and yellow colors. Numbers are presented twice, once in pink and once in yellow, so the client must ignore the distracter item (e.g. start at pink 1, avoid pink 2 to select yellow 2, avoid yellow 3 to select pink 3, etc.).	Baseline, week 2, 4 and 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digit Symbol Substitution Test (DSST)	The Digit Symbol Substitution Test (DSST), a coding task in which digits are substituted with a simple symbol. The task involves attention, processing speed, and executive functioning, and has shown sensitivity-to -change in MDD populations.22 DSST score is calculated as the total number of correct symbols within a 90-s period (possible score range 0-133), with higher scores reflecting better performance.	screen

Collaborators and Investigators

• Sponsor: Peking University Sixth Hospital
• Investigators: Principal Investigator: Xiaozhen Lv, Ph.D, Peking University Sixth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Cognitive Impairment; Randomized Controlled Trial; Major Depressive Disorder; Neuroimaging; Bright Light Therapy; Magnetic Response Imaging
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Mood Disorders; Depressive Disorder; Cognitive Dysfunction; Depressive Disorder, Major
• Other Study ID Numbers: 7262156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No