MicroRNA Correlates of Childhood Maltreatment and Suicidality

Purpose

This is a research study to find out if childhood trauma and stress are associated with depression or suicidal risk. The study will assess the effects of both short-term and long-term stress on biomarker (e.g. miRNA [MiRNA]) levels. miRNAs are a type of RNA (genetic material that is translated into protein) that are found in throughout the body and blood. They are called microRNA because their size is much smaller than typical RNA molecules. miRNAs are highly responsive to environment. This responsiveness is reflected in their expression in individuals who are affected by environment such as stress. The investigators are gathering genetic material, including DNA and RNA, from each participant. The RNA will be taken from the small vesicles and cells in the participant's blood and analyzed. The vesicles are small objects that occur normally in the blood and that contain RNA. This information may help us to understand the cause of mental illness and to improve medical and psychiatric care in the future. There will be 450 participants enrolled in this study.

Conditions

  • Major Depressive Disorder
  • Suicidal Ideation

Eligibility

Eligible Ages
Between 18 Years and 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  1. Age 18-60 2. Physically healthy 3. Willing and able to provide informed consent 5. Diagnosis of MDD or No history of mental illness

Exclusion Criteria

  1. Pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy screen) 2. Post-partum state (being within 2 months of delivery or miscarriage) 3. Homicide risk as determined by clinical interview 4. A lifetime history of psychotic disorder 5. Any history of dissociation or dissociative disorder 6. Bipolar disorder 7. Pervasive developmental disorder 8. Cognitive disorder 9. Cluster A personality disorder 10. Borderline personality disorder 11. Anorexia nervosa 12. Alcohol or drug dependence (except nicotine and caffeine) within the last month or the use of any hallucinogen (except cannabis), including phencyclidine in the last month (NOTE that a positive UDS is not exclusionary except for hallucinogens, methamphetamine, or cocaine. People presenting intoxicated with alcohol may be included when a Breathalyzer test (Alco-Sensor IV) is negative as long as there is no history of recent dependence. 13. Recent myocardial infarction 14. Unstable angina 15. Active neoplasm in the past 6 months 16. Immunosuppressive or corticosteroid therapy within the last month, with the following exceptions: any inhaled, intranasal, topical or vaginal corticosteroids are allowed. 17. Chemotherapy 18. Head injury with loss of consciousness in the past 6 months

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Other

Arm Groups

ArmDescriptionAssigned Intervention
MDD with elevated CM and suicidality scores Major Depressive Disorder with elevator childhood maltreatment and suicidality scores.
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST
MDD with CM history but lower suicidality Major Depressive disorder with childhood maltreatment history but lower suicidality scores.
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST
MDD without CM but with elevated suicidality Major Depressive Disorder without childhood maltreatment, but with elevated suicidality scores.
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST
MDD without CM but with lower suicidality Major Depressive Disorder without childhood maltreatment but with lower suicidality scores.
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST
Healthy controls with CM history Healthy controls with childhood maltreatment history,
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST
Healthy controls without CM history Healthy controls without childhood maltreatment history.
  • Other: Trier Social Stress Test
    The TSST is a standardized test to induce acute psychological stress in humans. Participants will abstain from caffeine for 12 hours and nicotine for 2 hours prior to the test. An IV butterfly catheter will be placed in an arm vein and flushed with saline. Participants will rest for 15 minutes. A 10ml baseline blood sample will be drawn. They will perform the TSST task and then have 10ml of blood drawn at 0, 15, 30, 60, and 90 minutes post-TSST.
    Other names:
    • TSST

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233
Contact:
Melissa Alexander
205-934-2484
lalexander@uabmc.edu

UAB Huntsville Regional Medical Campus
Huntsville, Alabama 35294
Contact:
Allison M Stewart, BA
256-551-4431
allisonstewart@uabmc.edu

More Details

Status
Recruiting
Sponsor
University of Alabama at Birmingham

Study Contact

Allison Stewart, BA
256-551-4428
allisonstewart@uabmc.edu

Detailed Description

The purpose of the study is to determine if the relationship between a history of childhood maltreatment (CM) and suicide risk is associated with alterations in the expression and epigenetic modification of specific microRNAs (miRNAs), thereby providing a molecular signature of suicide risk in people with CM. miRNAs are short regulatory RNAs that transduce environmental events into changes in protein synthesis in cells. The environment can induce permanent changes in miRNA expression. Aim 1 is to identify a set of neural-derived exosomal miRNAs that are associated with the interaction of suicidality and CM. Aim 2 is to examine whether an acute experimental stressor, the Trier Social Stress Test (TSST), impacts the expression of these miRNAs in suicidal patients with and without CM. Aim 3 will examine potential mechanisms by which altered miRNAs may contribute to CM-associated suicidal behavior. Aim 4 will examine if changes in CM-associated miRNAs are explained by modifications in their DNA methylation.