Overview

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.

Eligibility

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.