Efficacy of Spectrally Optimized Light on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms

Efficacy of Spectrally Optimized Light on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms Study

This study aims to validate the therapeutic efficacy and safety of spectrally optimized light (SOL) 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 patients with cognitive impairment and examine the mediating effect of the HPC-dlPFC neural circuit on the cognitive improvements induced by SOL treatment in MDD-CI patients. Patients with MDD-CI are required to only receive selective serotonin reuptake inhibitors (SSRIs) as primary medication for at least one week or not do anything treatment before. SOL is a kind of Bright Light Therapy(BLT). Qualified 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 (placebo). The intervention will last for four weeks. The participants will be followed once in a week during intervention and in 4th week after intervention. Demographic information will be collected at baseline, cognitive function will be evaluated at baseline, 2nd, ,4th and 8th weekends after intervention beginning. and other symptoms such as depression, anxiety and sleep were assessed at baseline, 1st, 2nd, 3rd ,4th and 8th weekends after intervention beginning.Moreover, structural and functional MRI scans will be made at baseline and after four weeks intervention. During intervention, patients with MDD-CI will keep a record of daily light exposure duration, complete the daily sleep diary as well.

Study Overview

• Status: Not yet recruiting
• Conditions: Cognitive Impairment; Major Depressive Disorder (MDD); Neuroimaging; Bright Light Treatment
• Intervention / Treatment: Device: dim red light(placebo); Device: bright light

Detailed Description

This study was designed as a randomized controlled study. It focuses on patients with MDD-CI, with an experimental group and a control group established. The experimental group was treated with one of six SSRIs, including Fluoxetine, Paroxetine, Sertraline, Citalopram, Fluvoxamine, and Escitalopram. The medication maintained 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 (placebo). The intervention lasts for four weeks (six days per week, 45 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 the Chinese version of Measurement Consensus Cognitive Battery (MCCB),The Chinese Biref Cognitive Test(C-BCT),and Perceived Deficits Questionnaire(PDQ)at baseline, 2nd, 4th and 8th weekend after intervention beginning. Other clinical symptoms will be assessed by The 17-item Hamilton Depression Rating Scale (HAMD-17),Hamilton Anxiety Rating Scale (HAMA), Clinical Global Impression (CGI), Young Mania Rating Scale, (YMRS), Quick Self Rating Depression Symptoms Scale (QIDS), 7-item Generalized Anxiety Disorder Scale (GAD-7) ,Pittsburgh sleep quality index (PSQI),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, 1st, 2nd, 3rd, 4th and 8th weekends after intervention beginning. At the same time, the Safety and Applicability of the intervention during the treatment process were investigated using the Side Effects Rating Scale for Serotonin Specific Reuptake Inhibitors (SERS-SSRIs) and the Treatment Compliance Record Form.

• 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
      • Peking University Sixth Hospital
      • Contact: Xiaozhen Lv, Ph.D; Phone Number: +8601062723705; Email: lxz120300@163.com
  • Shanxi
    • Yanan, Shanxi, China
      • 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. current Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnosis of Major Depressive Disorder, first episode or recurrence;
2. age 18-60 years; gender no-limited;
3. the severity of MDD symptoms must be >14 scores on the Hamilton Depression Rating Scale-17 (HAMD-17);
4. with cognitive dysfunction currently,defined as a total score of ≤ 70 on the Digit Symbol Substitution Test (DSST);
5. eligible patients have received Selective Serotonin Reuptake Inhibitors(SSRIs) at stable dosages for at least 1 week or not;
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 major depressive disorder according to DSM-5 criteria;
2. the scores on YMRS are >8;
3. Individuals who have undergone other intervention in addition to SSRIs whinin the past six month or now, or who plan to do that in one month;
4. Individuals with strong self-blame, self-harm, or suicidal tendencies(HDRS-17 suicide item score ≥ 3)
5. Individuals 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. Individuals with any degree of retinal pathology, including retinal dystrophy, age-related macular degeneration, diabetic retinopathy, cataracts, glaucoma, or other ocular diseases;
7. Individuals 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. Individuals with contraindications to magnetic resonance imaging (MRI), such as the presence of non-MRI-safe metallic implants or claustrophobia.
10. Individuals deem unsuitable for inclusion in this study by the investigator for other reasons.

Withdrawal and Termination Criteria：

1. Participants meet one of the exclusion criteria above after enrollment
2. current individuals' treatment regimen need change;
3. Participants who fail to cooperate or voluntarily withdraw from the study;
4. Due to severe adverse events, participants are unable to tolerate phototherapy.
5. 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 18-60 years; gender no-limited; and right-handed;
2. without cognitive dysfunction currently,defined as a total score of ≤ 70 on the Digit Symbol Substitution Test (DSST)
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 lifetime diagnosis of any psychiatric disorders, or history of substance/drug abuse or dependence;
2. Currently or previously diagnosed with 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. Individuals with contraindications to magnetic resonance imaging (MRI), such as the presence of non-MRI-safe metallic implants or claustrophobia.
6. Individuals 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: Dim red light control intervention; Patients with selective serotonin reuptake inhibitors (SSRIs) or not will be subjected to red light (placebo) therapy. The light source intensity was set at <200 lux and placed 0.5 meters away from the patient. Patients were exposed to the light source, staring at it for 2 seconds every 5 minutes. The red light therapy was administered for 40 minutes each day between 7:00 AM and 10:00 AM, lasting for four weeks.	Device: dim red light(placebo); Using a dim red light box as the placebo, with an intensity of <200lux and a main wavelength of 690.4nm
Experimental: Bright Light Therapy(BLT) with Spectrally Optimized Light(SOL); In addition to administering dose-stable antidepressant medication (Selective Serotonin Reuptake Inhibitors, SSRIs) to patients with MDD-CI, they also received Bright Light Therapy(BLT) with Spectrally Optimized Light(SOL). The bright light source intensity is set at 10000 lux and placed 0.5 meters away from the patient. Every 5 minutes, patients are exposed to the light source, staring at it for 2 seconds each time. The bright light therapy was administered for 40 minutes each day between 7:00 AM and 10:00 AM, 6 days per week, lasting for four weeks.	Device: bright light; 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
Stroop Color-Word Test	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,the 2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention.
Hopkins Verbal Learning Test-Revised	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,the 2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention.
The Chinese Brief Cognitive Test（CBCT）	Cognitive functioning was assessed using the C-BCT, which is based on the MATRICS Consensus Cognitive Battery (MCCB) . It 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 depression population provide further evidence of its reliability and validity supporting the robustness of this scale for assessing cognitive function in these clinical groups.	baseline,the 2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention.
The Perceived Deficits Questionnaire for Depression（PDQ-D）	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,2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention.

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.	baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
Quick Inventory of Depressive Symptomatology-Self-Report（QIDS-SR）	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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
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.	baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
Asberg Side-Effect Rating Scale for Antidepressants	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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
Morningness-Eveningness Questionnaire-Self-Assessment（MEQ-SA）	The Morningness-Eveningness Questionnaire-Self-Assessment (MEQ-SA) is a widely-used self-rating tool designed to measure individual differences in circadian rhythm types, specifically distinguishing between "morning types" (also known as "larks") and "evening types" (also known as "owls").Each item on the MEQ-SA is scored on a specific scale, with the total score being the sum of all individual item scores. The scoring range typically varies from 16 to 86, with lower scores indicating a stronger tendency towards eveningness and higher scores suggesting a morningness predisposition. Specifically, scores of 41 or below are classified as "evening type," scores between 42 and 58 are considered "intermediate," and scores of 59 or above are categorized as "morning type."	baseline,2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention.
The Seasonal Pattern Assessment Questionnaire（SPAQ）	The Seasonal Pattern Assessment Questionnaire (SPAQ) is a comprehensive evaluation tool designed to assess the seasonal variations in various aspects of an individual's life, including sleep, social interactions, mood, weight, appetite, and energy levels.Each item on the SPAQ is scored on a specific scale, reflecting the degree to which the individual experiences seasonal variations in the respective domain. The total score, derived from the summation of individual item scores, provides an overall measure of seasonal pattern intensity. The scoring principles are designed to ensure that higher scores indicate more pronounced seasonal variations.	baseline
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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
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,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention.
Childhood Trauma Questionnaire (CTQ)	The Childhood Trauma Questionnaire (CTQ) was originally developed by American psychologist D. P. Bernstein et al. in 1994, initially comprising 70 items. In 1998, the developers abbreviated the instrument into a 28-item short form (CTQ-SF). [4] It was translated, revised, and introduced to the Chinese context by Zhao Xingfu, Zhang Yalin, Li Longfei, et al. in 2005. [6] [9] The revised CTQ-SF consists of 28 items encompassing five subscales: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. [1] [3] The scale employs a 5-point Likert scoring system, with higher scores indicating a greater severity of experienced abuse.	baseline
Life Event Scale (LES)	The Life Event Scale (LES) was developed by Yang Desen and Zhang Yalin in 1986, having been adapted from the Social Readjustment Rating Scale (SRRS) to suit the sociocultural context of China. The scale emphasizes individuals' subjective perceptions of life events, categorizing them into positive and negative events. The inventory comprises 48 life events commonly experienced in China, encompassing domains such as family life, work and study, and social interactions. Research indicates that negative life events are closely associated with various psychiatric disorders and psychosomatic diseases.	baseline
Clinical Global Impression（CGI）	The Clinical Global Impression Scale (CGI) usually is used to assess the performance of general psychopathology. CGI-S is used to estimate symptom severity and CGI-I for improvement .The CGI is a 7-point scale that requires a rating of illness severity at the time of assessment. Because severity estimation in the CGI is performed in relation to other patients, it is a subjective assessment tool.	baseline, 4th weekend after the start of the 4-week intervention

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 (Estimated): April 1, 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): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: January 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