Reevaluating the Placebo Effect: Impact on Depressive Symptoms and Brain Age in a Randomized Control
Poster No:
432
Submission Type:
Abstract Submission
Authors:
Huei-Yu Tsai1, Chun-Chao Huang2,3, Hui-Chun Huang4,5, Hsin-Fan Chiang2,3, Cheng‑Chih Hsieh2,3, Shih-Yang Wei2,3, Chen-Yuan Kuo1,6, Shen-Ing Liu3,4,7, Ching-Po Lin1,8,9
Institutions:
1Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan, 2Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan, 3Department of Medicine, MacKay Medical College, New Taipei City, Taiwan, 4Nursing and Management, MacKay Junior College of Medicine, Taipei, Taiwan, 5Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan, 6Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, 7Department of Psychiatry, MacKay Memorial Hospital, Taipei, Taiwan, 8Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, 9Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
First Author:
Co-Author(s):
Chun-Chao Huang
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Hui-Chun Huang
Nursing and Management, MacKay Junior College of Medicine|Department of Medical Research, MacKay Memorial Hospital
Taipei, Taiwan|Taipei, Taiwan
Nursing and Management, MacKay Junior College of Medicine|Department of Medical Research, MacKay Memorial Hospital
Taipei, Taiwan|Taipei, Taiwan
Hsin-Fan Chiang
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Cheng‑Chih Hsieh
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Shih-Yang Wei
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Department of Radiology, MacKay Memorial Hospital|Department of Medicine, MacKay Medical College
Taipei, Taiwan|New Taipei City, Taiwan
Chen-Yuan Kuo
Institute of Neuroscience, National Yang Ming Chiao Tung University|Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Taipei, Taiwan|Taipei, Taiwan
Institute of Neuroscience, National Yang Ming Chiao Tung University|Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Taipei, Taiwan|Taipei, Taiwan
Shen-Ing Liu
Department of Medicine, MacKay Medical College|Nursing and Management, MacKay Junior College of Medicine|Department of Psychiatry, MacKay Memorial Hospital
New Taipei City, Taiwan|Taipei, Taiwan|Taipei, Taiwan
Department of Medicine, MacKay Medical College|Nursing and Management, MacKay Junior College of Medicine|Department of Psychiatry, MacKay Memorial Hospital
New Taipei City, Taiwan|Taipei, Taiwan|Taipei, Taiwan
Ching-Po Lin
Institute of Neuroscience, National Yang Ming Chiao Tung University|Brain Research Center, National Yang Ming Chiao Tung University|Department of Education and Research, Taipei City Hospital
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan
Institute of Neuroscience, National Yang Ming Chiao Tung University|Brain Research Center, National Yang Ming Chiao Tung University|Department of Education and Research, Taipei City Hospital
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan
Introduction:
Major Depressive Disorder (MDD) is a prevalent global health concern characterized by persistent depressed mood, functional impairment and severe health risks, including suicide. MDD has been associated with accelerated brain aging and cognitive decline, and structural brain atrophy, highlighting its profound impact on neurological health. [1]. Bright Light Therapy (BLT) shows promise as an adjunctive treatment by stimulating retinal circuitry and modulating brain serotonergic pathways [2, 3]. Research indicates that combining BLT with antidepressants can significantly improve treatment response, remission rates [4], and cognition [5]. However, it remains uncertain whether BLT can influence brain age and whether its clinical benefits are associated with alterations in brain age. This current study employed a retrospective clinical trial analysis and brain age modeling to investigate the effects of BLT on brain age in individuals with MDD and its association with symptom improvement.
Methods:
The double-blind, randomized controlled trial was conducted at MacKay Memorial Hospital's Taipei and Tamsui branches from June 2019 to April 2020. The inclusion criteria were: 1) aged ≥ 20; 2) diagnosed with MDD for ≥ 6 weeks; 3) Hamilton Depression Rating Scale (HAMD-24) score > 12; 4) stable antidepressant medication for ≥ 4 weeks; 5) no other psychiatric and medical conditions such as bipolar disorder, substance use, and physical illness. Participants were randomly assigned into two groups: 1) the BLT group: 10,000-lux white light therapy; 2) the dim red light (dRL) group: 70-lux red light therapy. All participants received standard instructions: 1) 30-minute daily light exposure in the morning; 2) Lightbox placement 40-75 cm from eyes; 3) 4-week treatment duration. Compliance and side effects were monitored at 1, 2, and 4 weeks. MRI scans were performed at baseline and after 4 weeks using identical Siemens 1.5T whole-body MRI scanner.
T1-weighted MRI data from 1,482 healthy participants (ages 18–92, 681 males, 801 females) were used to construct structural covariance network (SCN)-based brain age models [6]. In addition to constructing a global-brain age model, we developed four cognitive domain-specific brain age models, including executive function, memory, language, and vision, derived from meta-analytic findings. [7]. Finally, these five brain age models were applied to the clinical dataset to estimate predicted brain age and calculate the brain age gap (BAG).
Subsequently, statistical analyses included the Mann-Whitney U test for between-group differences and the Wilcoxon signed-rank test for pre- and post-therapy comparisons of HAMD-24, PHQ-9, and BAG. A linear regression and Pearson's correlation assessed the relationship between the average daily light therapy exposure time and the change in BAG. Analyses were conducted with a two-tailed significance of 0.05 using IBM SPSS.
T1-weighted MRI data from 1,482 healthy participants (ages 18–92, 681 males, 801 females) were used to construct structural covariance network (SCN)-based brain age models [6]. In addition to constructing a global-brain age model, we developed four cognitive domain-specific brain age models, including executive function, memory, language, and vision, derived from meta-analytic findings. [7]. Finally, these five brain age models were applied to the clinical dataset to estimate predicted brain age and calculate the brain age gap (BAG).
Subsequently, statistical analyses included the Mann-Whitney U test for between-group differences and the Wilcoxon signed-rank test for pre- and post-therapy comparisons of HAMD-24, PHQ-9, and BAG. A linear regression and Pearson's correlation assessed the relationship between the average daily light therapy exposure time and the change in BAG. Analyses were conducted with a two-tailed significance of 0.05 using IBM SPSS.
Results:
The study included 21 participants in the BLT group and 18 in the dRL group with similar demographics (Table 1). Both groups showed significant improvements in HAMD-24 and PHQ-9 scores without intergroup differences. Although there were no group differences in BAG, the combined group had a significantly younger BAG in global (p = 0.040), vision (p = 0.036), and language (p = 0.033) domains (Table 2). Additionally, patients with improvement in PHQ-9 scores showed reduced BAG in global (p = 0.043) and executive function (p = 0.035) domains.
·Table 1. Demographic data for the control and experimental groups.
·Table 2. Global and cognition-specific brain ages in each group and the combined whole group.
Conclusions:
In summary, our study revealed that BLT alone did not significantly change brain age. However, the combined treatment group showed clinical improvements and indicators of younger brain age. These results hint at a complex interaction between placebo effects and depression symptom reduction, especially in global and executive function, potentially illuminating the neurobiological underpinnings of depression treatment.
Brain Stimulation:
Non-Invasive Stimulation Methods Other 2
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
Imaging Methods Other
Keywords:
Cognition
MRI
Psychiatric Disorders
Therapy
1|2Indicates the priority used for review
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2. Kang, S.G. & Cho, S.E., Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder. Int J Mol Sci 2020, 21(6).
3. Li, X. & Li, X., The Antidepressant Effect of Light Therapy from Retinal Projections. Neurosci Bull 2018, 34(2):359-368.
4. Martiny, K., et al., Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand 2005, 112(2):117-125.
5. Huang, X., Tao Q, Ren C, A Comprehensive Overview of the Neural Mechanisms of Light Therapy. Neurosci Bull 2024, 40(3):350-362.
6. Kuo, C.Y., et al., Large-Scale Structural Covariance Networks Predict Age in Middle-to-Late Adulthood: A Novel Brain Aging Biomarker. Cereb Cortex 2020, 30(11):5844-5862.
7. Beam, E., et al., A data-driven framework for mapping domains of human neurobiology. Nature neuroscience, 2021. 24(12): p. 1733-1744.