Neuro-affective Response to Light in Depressed Adolescents and Young Adults

Study Overview
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Brief Summary
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The goal of this neuroimaging pilot study is to understand developmental differences in the impact of therapeutic wavelength light (blue light) versus a non-therapeutic wavelength (red light) on emotional brain function in depression. The main questions this study aims to answer are: Does acute exposure to blue light (vs red light) stabilize emotional brain function in depressed individuals? Are stabilizing effects of blue light (vs red light) stronger for blue light in adolescents than young adults? Participants will complete: A magnetic resonance imaging brain scan, in which we will examine the effect of blue versus red light on emotional brain function at rest and in response to rewards and losses. A pupillometry test of sensitivity to blue vs red light Clinical interviews and surveys Screening measures for drug and alcohol use, MRI safety, and current pregnancy [if relevant] Home sleep tracking with sleep diary and actigraphy for one week

Official Title
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Neuro-affective Response to Light in Depressed Adolescents and Young Adults

Conditions
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Depression in Adolescence, Depression in Adults

Intervention / Treatment
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* Other: Blue Light
* Other: Red Light


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-5 major depressive episode (If <18yr) Parent or guardian can attend the baseline clinical interview Exclusion Criteria: Unable to read and write in English Intellectual disability. Left or mixed handedness Use of psychotropic medication other than stable Selective Serotonin Reuptake Inhibitor (SSRI) medication (> 2 months) Lifetime bipolar disorder or schizophrenia, or substance/alcohol disorder in the past 3 months. Factors influencing light and color sensitivity (i.e., color-blindness, serious ophthalmological conditions, photo-sensitizing medication). Factors influencing the ability to maintain a stable sleep schedule (i.e., shift work, severe sleep disorders, extremely late or early sleep schedule). Severe medical illness, neurological disorders, or history of head trauma. Current pregnancy or nursing MRI contraindication (e.g., metals in the body, recent tattoo, claustrophobia) Positive alcohol or substance use screen at MRI visit

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 30 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All participants will receive blue and red light exposures; order of red vs. blue light will be counterbalanced across participants.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blue then Red Light<br>Blue light (480 nm) then Red light (640 nm) | Other: Blue Light<br>* Blue light exposure<br>Other: Red Light<br>* Red light exposure<br>|
| Experimental: Red Light then Blue Light<br>Red light (640 nm) then Blue light (480 nm) | Other: Blue Light<br>* Blue light exposure<br>Other: Red Light<br>* Red light exposure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amygdala cerebral blood flow during Blue vs Red light exposure | Cerebral blood flow will be assessed using pseudo-continuous arterial spin labeling collected during blue and red light exposures. Regional cerebral blood flow in the amygdala region of interest will be examined. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventral Striatum cerebral blood flow during Blue vs Red light exposure | Cerebral blood flow will be assessed using pseudo-continuous arterial spin labeling collected during blue and red light exposures. Regional cerebral blood flow in the ventral striatum region of interest will be examined. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Amygdala activity (loss>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within an amygdala region of interest on loss versus neutral (no win/no loss) trials. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventral Striatum activity (punish>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within a ventral striatum region of interest on win versus neutral (no win/no loss) trials. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medial prefrontal cortex cerebral blood flow during Blue vs Red light exposure | Cerebral blood flow will be assessed using pseudo-continuous arterial spin labeling collected during blue and red light exposures. Regional cerebral blood flow in the medial prefrontal region of interest will be examined. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Insula cerebral blood flow during Blue vs Red light exposure | Cerebral blood flow will be assessed using pseudo-continuous arterial spin labeling collected during blue and red light exposures. Regional cerebral blood flow in the insula regions of interest will be examined. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventromedial prefrontal cortex cerebral blood flow during Blue vs Red light exposure | Cerebral blood flow will be assessed using pseudo-continuous arterial spin labeling collected during blue and red light exposures. Regional cerebral blood flow in the ventromedial prefrontal cortex regions of interest will be examined. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Amygdala-whole brain functional connectivity (loss>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Functional connectivity is defined as a psychophysiological interaction between the seed region (amygdala) and the whole brain on loss versus neutral (no win/no loss) trials | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventromedial prefrontal cortex activity (loss>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within the ventromedial prefrontal cortex region of interest on loss versus neutral (no win/no loss) trials. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Insula activity (loss>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within the insula region of interest on loss versus neutral (no win/no loss) trials. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Medial prefrontal cortex activity (win>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within the medial prefrontal region of interest on win versus neutral (no win/no loss) trials. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventral striatum-whole brain functional connectivity (win>neutral) during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Functional connectivity is defined as a psychophysiological interaction between the seed region (ventral striatum) and the whole brain. | Collected during the blue and red light exposures during the MRI scan at the lab visit | 
| Ventromedial prefrontal cortex activity, insula, and medial prefrontal activity, and amygdala- and ventral striatum whole brain functional connectivity (response bias; B') during Blue vs Red light exposure | This outcome will be measured during the an auditory probabilistic reward task, which is a computerized fMRI behavioral task. Activation is defined by blood oxygen dependent signal within the above regions of interest using a response bias metric (B'). Functional connectivity is defined as a psychophysiological interaction between the seed regions (amygdala, ventral striatums) and the whole brain. | Collected during the blue and red light exposures during the MRI scan at the lab visit |