Stress Effects on Depression and Suicidal Thoughts

Recruiting at 1 trial location

Overseen By Jessica Weed, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressives, Corticosteroids, Chemotherapy, others

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

450 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive or corticosteroid therapy, you may need to stop, unless it's inhaled, intranasal, topical, or vaginal corticosteroids.

Is the Trier Social Stress Test (TSST) safe for humans?

The Trier Social Stress Test (TSST) has been used in studies with healthy humans and has shown to increase stress-related hormones like cortisol, but there is no specific mention of harmful effects, suggesting it is generally safe for use in controlled settings. ^{1 2 3 4 5}

How does this treatment for stress effects on depression and suicidal thoughts differ from other treatments?

This treatment may focus on addressing the unique relationship between stress and cognitive-affective symptoms of depression, as well as the specific impact of severe life stressors on suicidal thoughts, which is not typically the primary focus of standard depression treatments. ^{2 3 4 6 7}

What is the purpose of this trial?

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.

Research Team

Yogesh Dwivedi, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults aged 18-60 who are physically healthy. Participants can either have a diagnosis of Major Depressive Disorder (MDD) or no history of mental illness at all, and they must be able to understand and agree to the study's procedures.

Inclusion Criteria

Age 18-60

Physically healthy

Willing and able to provide informed consent

Exclusion Criteria

You have been diagnosed with Bipolar Depression

You have been diagnosed with Psychosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Collection of genetic material, including DNA and RNA, from each participant

1 week

1 visit (in-person)

Experimental Stressor

Participants undergo the Trier Social Stress Test (TSST) to assess miRNA expression changes

24 hours

1 visit (in-person)

Follow-up

Participants are monitored for changes in miRNA expression and methylation levels

4 weeks

Treatment Details

Interventions

• Trier Social Stress Test

Trial Overview The study is looking into how childhood trauma and stress might lead to depression or suicidal thoughts by testing levels of microRNA in the blood. The Trier Social Stress Test will be used as part of this research.

Participant Groups

Group I: MDD without CM but with lower suicidality Experimental Treatment 1 Intervention

Major Depressive Disorder without childhood maltreatment but with lower suicidality scores.

Group II: MDD without CM but with elevated suicidality Experimental Treatment 1 Intervention

Major Depressive Disorder without childhood maltreatment, but with elevated suicidality scores.

Group III: MDD with elevated CM and suicidality scores Experimental Treatment 1 Intervention

Major Depressive Disorder with elevator childhood maltreatment and suicidality scores.

Group IV: MDD with CM history but lower suicidality Experimental Treatment 1 Intervention

Major Depressive disorder with childhood maltreatment history but lower suicidality scores.

Group V: Healthy controls without CM history Experimental Treatment 1 Intervention

Healthy controls without childhood maltreatment history.

Group VI: Healthy controls with CM history Experimental Treatment 1 Intervention

Healthy controls with childhood maltreatment history,

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Exposure therapy methods, specifically Prolonged Exposure (PE) and Virtual Reality Exposure (VRE), significantly reduced suicidal ideation (SI) in active duty military personnel compared to a wait-list control, with a lower probability of SI post-treatment (OR = 0.23).

The study found that reductions in SI occurred early in treatment and were linked to decreases in PTSD symptoms, indicating that PE and VRE can effectively address suicidality in individuals with PTSD without being influenced by baseline SI levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prolonged exposure and virtual reality exposure on suicidal ideation in active duty soldiers: An examination of potential mechanisms. Norr, AM., Smolenski, DJ., Reger, GM.[2019]

In a study involving 54 non-endogenous depressive patients who had attempted suicide, the results of three consecutive dexamethasone suppression tests (DSTs) did not correlate with the lethality of their suicide attempts.

The high rate of nonsuppression in DST results among these patients is likely influenced by stress and various drug interactions, suggesting that these factors may complicate the interpretation of DST in assessing depression severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dexamethasone suppression test repeated after a suicide attempt]. Wilmotte, J., Van Wettere, JP., Depauw, Y., et al.[2015]

In a study of 1,058 psychiatric patients, 64.7% reported experiencing at least one stressful life event (SLE) in the past three months, which correlated with both recent and future suicidal thoughts and behaviors (STBs).

Specific SLEs, particularly those related to interpersonal rejection, loss, homelessness, and academic failure, were found to significantly increase the risk of STBs, indicating these areas may require heightened clinical attention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stressful Life Events and Near-term Suicidal Risk in a Clinical Population. Cohen, LJ., Hernandez, M., Mokhtar, R., et al.[2023]

In a study of 67 adult women, those with a history of suicide attempts showed a significantly higher cortisol response to social stress compared to those without such a history, particularly in individuals with low depression and high impulsivity traits.

All patients experienced increased psychological pain, negative mood, and anxiety immediately after social stress, but those with a history of suicide attempts had a slower recovery of positive mood, indicating that impulsivity may heighten emotional distress and vulnerability in stressful situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impulsiveness level influences the salivary cortisol response and social stress sensitivity in suicidal patients. Alacreu-Crespo, A., Hidalgo, V., Girod, C., et al.[2023]

In a study involving 32 healthy young males, acute psychosocial stress from the Trier Social Stress Test significantly increased serum levels of brain-derived neurotrophic factor (BDNF) and cortisol, indicating a physiological response to stress.

This research highlights the potential beneficial effects of acute psychosocial stress on BDNF levels, which are important for brain plasticity and development, and suggests further exploration of these effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of acute psychosocial stress on the brain-derived neurotrophic factor in humans - a randomized cross within trial. Hermann, R., Schaller, A., Lay, D., et al.[2022]

In a study of 59 individuals with major depression, severe life stress was primarily linked to cognitive-affective symptoms rather than somatic symptoms, highlighting the specific impact of stress on mental processes and emotions.

The research found a strong connection between severe life events occurring before the onset of depression and suicidal thoughts, suggesting that early life stressors may significantly influence the severity and type of depressive symptoms experienced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life stress and the symptoms of major depression. Monroe, SM., Harkness, K., Simons, AD., et al.[2019]

In a study of 33 euthymic females with a history of major depressive episodes, brain activity in the orbitofrontal cortex during social exclusion was negatively correlated with daily psychological pain in those who had attempted suicide, indicating a link between neural processing and real-world emotional experiences.

This suggests that altered brain responses to social exclusion may contribute to psychological pain and suicide risk, highlighting the importance of understanding individual vulnerabilities in mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal activity during experimental ostracism and daily psychache in suicide attempters. Olié, E., Husky, M., Bars, EL., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of prolonged exposure and virtual reality exposure on suicidal ideation in active duty soldiers: An examination of potential mechanisms. [2019]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Dexamethasone suppression test repeated after a suicide attempt]. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Stressful Life Events and Near-term Suicidal Risk in a Clinical Population. [2023]

4. England pubmed.ncbi.nlm.nih.gov

The impulsiveness level influences the salivary cortisol response and social stress sensitivity in suicidal patients. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Effect of acute psychosocial stress on the brain-derived neurotrophic factor in humans - a randomized cross within trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Life stress and the symptoms of major depression. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prefrontal activity during experimental ostracism and daily psychache in suicide attempters. [2021]