Major Depressive Disorder (MDD), Neuroimaging, Bright Light Treatment, Cognitive Impairment
Conditions
Keywords
Major Depressive Disorder, Neuroimaging, Magnetic Response Imaging, Bright Light Therapy, Cognitive Impairment, Randomized Controlled Trial
Brief summary
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.
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.
Interventions
DEVICEbright light
Using a hybrid white light box with independent intellectual property rights, with an intensity of 10000lux and a main wavelength of 476.4nm
DEVICEdim red light(placebo)
Using a dim red light box as the placebo, with an intensity of \<200lux and a main wavelength of 690.4nm
Sponsors
Peking University Sixth Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
Patients will be coded according to the order of enrollment and randomly assigned to the experimental group or the control group by the random number method.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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、
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroop Color-Word Test | baseline,the 2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention. | 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. |
| Hopkins Verbal Learning Test-Revised | 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 (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. |
| The Chinese Brief Cognitive Test（CBCT） | baseline,the 2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention. | 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. |
| The Perceived Deficits Questionnaire for Depression（PDQ-D） | baseline,2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale-17（HDRS-17） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Generalized Anxiety Disorder-7（GAD-7） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Quick Inventory of Depressive Symptomatology-Self-Report（QIDS-SR） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Pittsburgh Sleep Quality Inventory（PSQI） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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 |
| Young Mania Rating Scale（YMRS） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Asberg Side-Effect Rating Scale for Antidepressants | 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 (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. |
| Morningness-Eveningness Questionnaire-Self-Assessment（MEQ-SA） | baseline,2nd and 4th weekends after the start of the 4-week intervention,and the 4th weekend after the 4-week intervention. | 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." |
| The Seasonal Pattern Assessment Questionnaire（SPAQ） | baseline | 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. |
| Quality of Life Enjoyment and Satisfaction Questionnaire,Short Form（Q-LES-Q-SF） | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Sheehan disability scale (SDS) | baseline,1st,2nd,3rd and 4th weekends after the start of the 4-week intervention,the 4th weekend after the 4-week intervention. | 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. |
| Childhood Trauma Questionnaire (CTQ) | baseline | 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. |
| Life Event Scale (LES) | baseline | 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. |
| Clinical Global Impression（CGI） | baseline, 4th weekend after the start of the 4-week intervention | 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. |
Countries
China
Contacts
CONTACTXiaozhen Lv, Ph.D
PRINCIPAL_INVESTIGATORXiaozhen Lv, Ph.D
Peking University Sixth Hospital
Outcome results
None listed