A Longitudinal Study of Inflammatory Pathways in Depression

NCT04159207 | Completed

• 2 other identifiers: 190101R01MH118211-01A1
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

Suicide accounts for at least 1 million deaths globally each year. This is likely a significant underestimate, because suicide is under-reported in many countries. In the US, over 42,000 people die from suicide annually. Despite increased focus on identification and treatment, the rate of suicide has increased steadily over the past 15 years. Our project aims both to improve our understanding of factors that increase the risk for suicide by comparing blood biomarkers associated with inflammation in patients with depression without suicidal behavior and patients with depression and suicidal behavior. The 160 individuals in this study will be followed with psychiatric assessments and blood samples at repeated time points over one year.

Conditions

Major Depressive Disorder; Suicide, Attempted

Keywords

Depression; Suicide; Inflammation; Kynurenine; Cytokine

Outcome Measures

Primary Outcomes (5)

• Suicidal behavior of participants

  The presence of suicidal behavior over one year will be classified as yes/no as the primary outcome measure. The Identification of participants with suicidal behavior at each study time point will be achieved by assessment using the Columbia Suicide Severity Rating Scale (C-SSRS) regarding attempt, interrupted or aborted attempt, or preparatory acts over the past 7 days.

  One year.

• Establish metabolic biomarkers that indicate risk for suicidal behavior

  Evaluate if metabolic biomarkers are predictive of suicidal behavior (planning, attempting) among patients with depression. Metabolites will be measured by high-pressure liquid chromatography, ultra-high performace liquid-chromatography and gas-chromatography mass-spectrometry). The main metabolite biomarker outcomes are quinolinic, kynurenic and picolinic acids as well as 3-HK and kynurenine (nM).

  One year.

• Establish inflammatory biomarkers that indicate risk for suicidal behavior

  Evaluate if inflammatory biomarkers are predictive of suicidal behavior (planning, attempting) among patients with depression. Inflammatory markers will be measured using high-sensitivity ELISAs, Mesoscale platform or Luminex platforms. The main cytokine outcomes are TNF-alpha and IL-6 (pg/ml).

  One year.

• Determine epigenetic marks in blood cells from patients with suicidal behavior

  DNA methylation will be measured by Illumina Infinum methylationEPIC BeadChip microarrays, and compacted between patients with suicidal behavior and patients without suicidal behavior.

  One year.

• Functional validation of the significant methylation changes

  mRNA will be quantified by qPCR in the same peripheral blood samples as used for the EPIC array for functional validation of the significant methylation changes.

  One year.

Study Arms (1)

A Longitudinal Study of Inflammatory Pathways in Depression

We target to recruit 80 patients with Major Depression Disorder diagnosis and 80 patients with Major Depression Disorder with suicidal behavior.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People who are above age of 18, have a Major Depressive Disorder diagnosis and no ongoing immune disorders.

You may qualify if:

• Men and women ages 18 years and older will be included in the study.
• who are diagnosed with MDD by SCID but do not endorse current or past suicidal behaviors.
• who are diagnosed with MDD by SCID and endorse current suicidal behavior as defined by C-SSRS (preparatory acts, aborted or interrupted attempts, as well as completed attempts).
• English speaking.
• Willing and able to take part of the different steps in the study, including follow-up interviews and blood draws.

You may not qualify if:

• Vulnerable populations (e.g. incarcerated individuals).
• Subjects with dementia or otherwise cognitively impaired subjects with difficulty understanding the study procedures.
• Patients with a primary psychiatric diagnosis other than MDD.
• Patients with an active somatic disorder primarily involving the immune system (autoimmune diseases such as Crohns disease, multiple sclerosis, or rheumatoid arthritis; or hematological diseases such as lymphoma or leukemia).
• Patients on chronic and systemic immunomodulatory treatment. Examples are patients with a liver- or kidney transplant or medications used for disorders involving the immune system, as mentioned above. Examples of immunomodulatory treatments are cyclosporin, azathioprine, infliximab, corticosteroid treatment.
• Patients undergoing active treatment for any form of cancer (chemotherapy or immunomodulatory treatments).

Sponsors & Collaborators

• Van Andel Research Institute: lead
• Pine Rest Christian Mental Health Services: collaborator
• Columbia University: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Pine Rest Christian Mental Health Services

Grand Rapids, Michigan, 49501, United States

Location

Related Publications (36)

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Biospecimen

Retention: SAMPLES WITH DNA

blood draw

MeSH Terms

Conditions

Depressive Disorder, Major; Suicide, Attempted; Depression; Suicide; Inflammation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lena C Brundin, M.D.; Ph.D.

  Van Andel Research Institute

  PRINCIPAL INVESTIGATOR

• Eric Achtyes, M.D.

  Pine Rest Christian Mental Health Services

  PRINCIPAL INVESTIGATOR

• Joseph Mann, M.D.

  Columbia University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: November 12, 2019
• Study Start: October 1, 2019
• Primary Completion: August 30, 2023
• Study Completion: August 30, 2023
• Last Updated: April 6, 2025

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)