Mitochondrial Dysfunction, Inflammation, and White Matter Integrity in Youth With Mood Disorders

Study Overview
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Brief Summary
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This study consists of three separate appointments including a clinical assessment (interview and questionnaires), a blood draw, a social stress test, and a brain MRI.

Detailed Description
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This is a research study looking at the biology of mood disorders in youth. The investigator ask participants to come in for three visits. The first visit includes a diagnostic interview, some questionnaires, and a blood draw. The blood draw will take place at the Fairview Outpatient Lab. A trained technician will take about 4 teaspoons of blood from the participant's arm. This sample will be sent to Dr. Andreazza in Toronto, Ontario for further analysis. No results will be shared with the participant. The second visit would take place at the Fairview Riverside Ambulatory Research Center (ARC). This appointment will include the Trier Social Stress Test (TSST). For this, participants will be asked to prepare a short speech for 5 minutes and deliver that speech for in front of an audience with another task to follow. This task will be videotaped. After the participant has completed the speech task, the participant will be asked to complete a number of laptop games which will test for things like attention and memory. Participants will be asked to provide 5 saliva samples throughout the course of this visit so the investigators can look at Cortisol which is a hormone naturally found in saliva. The investigators will also ask participants to complete an additional set of 5 spit samples at home during the course of a normal day and bring those back to their next appointment. The third visit would take place at the Center for Magnetic Resonance Research (CMRR) and would include a brain MRI. The MRI scan is noninvasive and takes about 2 hours. Participants will be asked to provide a urine sample and complete a urine toxicology screen (drug test) and pregnancy test (if female) prior to the MRI scan. Participants may not participate if drug or pregnancy testing is positive. The MRI involves taking pictures of the brain, from which measures of the integrity of certain brain tissues can be derived. For the scan, participants will be asked to lie down quietly on a scanner bed. Once they are inside the scanner, it will start to take pictures. While in the scanner, participants will be doing things like resting, or listening to music.

Official Title
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Mitochondrial Dysfunction, Inflammation, and White Matter Integrity in Youth With Mood Disorders

Conditions
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Depression, Bipolar Disorder, Bipolar Disorder Not Otherwise Specified, Unspecified Mood Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - All Participants: Age 13-18 years old Both child and guardian are English speaking Inclusion Criteria - Patient Group: Has a diagnosis of a depressive disorder, a bipolar spectrum disorder (type 1, type 2, Unspecified), or an unspecified mood disorder based on the Diagnostic Statsitical Manual 5 (DSM-5) Inclusion Criteria - Healthy Controls Does not meet criteria for any psychiatric disorders based on the DSM-5 Does not have a family history of psychotic or mood disorders in first degree relative Exclusion Criteria: Past history of brain damage, a seizure disorder, increased intracranial pressure, history of head trauma with loss of consciousness for >15 minutes, history of stroke, mental retardation, or other serious neurological disorder MRI contraindications such as braces, metal implants, implanted medical devices, or claustrophobia Intelligence quotient < 80 Severe or acute medical illness A history of current (past 3 months) substance disorder (defined by DSM-5) with the exception of Nicotine Refusal to cooperate with study procedures Active suicidal ideation with intent Self-injury that requires medical attention (e.g. stitches) or gets significantly worse during the course of the study

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adolescents with Mood Disorders<br>Teens aged 13-18 with a diagnosis of a mood disorder. | |
| Adolescents with no Mental Health Diagnoses<br>13-18, no psychiatric d/o diagnosis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Analysis | Blood samples will be analysed for mitochondrial dysfunction and resulting oxidative damage to lipids, and protein and messenger ribonucleic acid levels of inflammatory cytokines | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Data | White matter integrity. Diffusion imaging data will be processed, following registration and motion correction, using a probabilistic tractography approach that will define and extract parameters such as fractional anisotrophy and radial diffusion from fiber bundles of interest. In this study we will focus on white matter tracts connecting fronto-limbic brain regions. Details about the tractography procedures can be found at http://surfer.nmr.mgh.harvard.edu/fswiki/Tracula | Up to 6 weeks after baseline | 
| Saliva Cortisol | Stress Functioning. Saliva samples from the Trier Social Stress Test will be stored in a freezer and sent as a complete batch to Trier, Germany. We will conduct repeated measures ANOVA tests on the cortisol data and examine group and group x time interactions. We will calculate the Area Under the Curve for each person's pattern of cortisol responses over time, and these values will be used in multivariate regression analyses below. | Up to 6 weeks of baseline | 
| Beck Depression Inventory (BDI-II) | Measures levels of depression in participants. Has information on suicidal ideation. If participants are suicidal, a member of research staff will talk with the participant and develop a safety plan with the adolescent and their parent. | Baseline and within 6 weeks of baseline | 
| Children's Depression Rating Scale - Revised (CDRS-R) | Measures levels of depression in participants. Has information on suicidal ideation. If participants are suicidal, a member of research staff will talk with the participant and develop a safety plan with the adolescent and their parent. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood Disorder