Explore the Neural Mechanism of Mindfulness Training to Reduce Loneliness in Depressed Older Adults

Study Overview
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Brief Summary
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Perceived loneliness causes a global health burden on older adults. Mindfulness training may be a feasible solution. Through our study, we expect that comprehensive and convincing neuroscientific evidence may support the efficacy underpinning mindfulness training in loneliness reduction.

Detailed Description
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In this aging and highly industrial society, elderly depression, particularly elderly loneliness, is a growing societal issue. Perceived loneliness not only causes tremendous suffering, disability, cognitive decline, and risk of dementia but also leads to increased mortality. Despite worldwide effort to solve the growing prevalence of loneliness in older adults, no single intervention stands out as universally effective and practical. The exact neural mechanism of loneliness and how the intervention against loneliness takes its effect in the brain remain unclear. Prior studies have indicated that perceived loneliness is associated with distorted cognition toward interpersonal interaction and heightened sympathetic nerve system.Mindfulness training is a discipline that the older adults in our society can readily relate to because the philosophy of mindfulness is similar to Buddhism. Mindfulness trains people to be aware of the surrounding environment and their presence in this environment. Combining the exercises of deep breathing and relaxation, one is taught to be aware of the emotion of oneself to regulate emotion. Mindfulness-based stress reduction (MBSR), a validated and systemized intervention, has been applied to the treatment of depression, anxiety, and insomnia. On the basis of the theory of mindfulness, the investigators estimate that mindfulness can reduce loneliness as well. Thus, the investigators aim to use MBSR in a group of older adults with depression to reduce loneliness. Our previous studies demonstrated that loneliness decreases the grey matter volume in reward system, disrupts the white matter structure, and heightens default-mode network activation. By combining a wearable device for sleep monitoring, heart rate variability measurement, and immune-related cytokine blood test, the investigators can associate these changes with clinical loneliness reduction and brain changes from magnetic resonance imaging. The investigators hope to validate MBSR as an effective intervention against loneliness and explore the supporting neural mechanism.

Official Title
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Explore the Neural Mechanism of Mindfulness Training to Reduce Loneliness in Depressed Older Adults: a Randomized Controlled Trial

Conditions
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Late Life Depression

Intervention / Treatment
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* Behavioral: Mindfulness based stress reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 55 years. Major depressive disorder (MDD). Exclusion Criteria: Inability to provide informed consent. Dementia, as defined by MMSE < 24 (<17 if illiterate or no education) and clinical evidence of dementia based on DSM-5 criteria. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms. Abuse of or dependence on alcohol or other substances within the past 3 months, and confirmed by study physician interview. High risk for suicide (e.g., active suicide ideation and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview). Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. Currently under psychotherapy or taking regular meditation or yoga practice (or had experience in these activities)

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness based stress reduction<br>Age > 55 years. Major depressive disorder (MDD). Right handiness with a score ≥ 24 on the MMSE | Behavioral: Mindfulness based stress reduction<br>* Mindfulness based stress reduction v.s.Relaxation<br>|
| Placebo Comparator: Relaxation<br>Age > 55 years. Major depressive disorder (MDD). Right handiness with a score ≥ 24 on the MMSE | Behavioral: Mindfulness based stress reduction<br>* Mindfulness based stress reduction v.s.Relaxation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loneliness UCLA | the severity of loneliness (the score range from 20-80,the lower score means worse) | Change from Baseline at 3 months | 
| Mindfulness | the effects of mindfulness(the score range from 20-100) | Change from Baseline at 3 months | 
| Ham D-17 | the insight(the score range from 0-2,the higher score means worse) | Change from Baseline at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal Learning & Memory | Word list of Wechsler Memory Scale-III Face memory task(the score range from 0-48,the higher score means better) | Change from Baseline at 3 months | 
| structural and functional connectivity | Brain MRI connectivity change | Change from Baseline at 3 months | 
| Interleukin-1α | IL-1α | Change from Baseline at 3 months | 
| Interleukin-1β | IL-1β | Change from Baseline at 3 months | 
| Interleukin-6 | IL-6 | Change from Baseline at 3 months | 
| Interleukin-12 | IL-12 | Change from Baseline at 3 months | 
| TGF-β1 | TGF-β1 | Change from Baseline at 3 months | 
| Total Brain-derived neurotrophic factor | Total BDNF | Change from Baseline at 3 months | 
| Free Brain-derived neurotrophic factor | Free BDNF | Change from Baseline at 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly depression, Mindfulness-based stress reduction (MBSR), MRI, autonomic nervous system