Cellular Aging and Neurobiology of Depression Study

NCT00285935 | Completed DMC

• 3 other identifiers: 10-00825R01MH083784K08MH126192
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 1

Brief Summary

We are conducting an eight week longitudinal study to learn if blood levels of certain naturally occurring compounds and genetic markers differ between patients with depression and healthy adults who are not depressed, and if any such differences relate to memory performance, mood, and neurobiology. We are also interested in how the gut microbiome is affected by antidepressant treatment. We will do this by comparing the unmedicated depressed patients with matched healthy controls at baseline and then following the depressed patients over the course of eight weeks of standardized antidepressant treatment to gauge which baseline abnormalities normalize over the course of treatment.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; MDD; Neurobiology; Selective Serotonin Reuptake Inhibitor; SSRI; Depression

Outcome Measures

Primary Outcomes (2)

• Depression ratings at baseline and Week 8

  baseline and Week 8

• Serum levels of steroids and neurosteroids at baseline and Week 8

  baseline and Week 8

Secondary Outcomes (2)

• Serum levels of oxidative stress markers at baseline and Week 8

  baseline and Week 8

• Serum levels of cytokines and immune markers at baseline and Week 8

  baseline and Week 8

Study Arms (1)

Treatment with SSRI

EXPERIMENTAL

Depressed participants will receive 8 weeks of treatment with one of the following serotonin-specific reuptake inhibitors: fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), escitalopram (Lexapro®) The specific drug used for treatment will be selected by the study clinician based on clinical interviews and the participants preferences. Participants will be monitored for response and side effects by study clinician and will return after 8 weeks for a follow up study visit.

Other: Standard Clinical Care with an SSRI

Interventions

Standard Clinical Care with an SSRI OTHER

Participants who enroll in this phase are treated with an FDA-approved SSRI in an open-label "treatment-as-usual" manner, in accordance with clinical practices and at a titration rate no more rapid than the manufacturer's recommendations. The duration of the treatment phase is 8 weeks. Other Name: fluoxetine (Prozac®), Sertraline (Zoloft®), citalopram (Celexa®), escitalopram (Lexapro®)

Treatment with SSRI

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

All participants must meet the following criteria: * Age 21-60 and able to give informed consent. * Not "needle phobic," by self-report. * English-speaking (to allow accurate use of behavioral rating scales and verbal cognitive tests). * Females of child-bearing capacity must be non-pregnant (confirmed by urine pregnancy test) and using effective non-hormonal birth control (e.g. abstinence, condoms, IUD). * Good general medical health; no significant uncontrolled illnesses that will invalidate the designated outcome measures. * Clinical labs (electrolytes, liver function test, CBC) with no clinically significant abnormalities that result in medical treatment that will invalidate the designated outcome measures. * Negative urine toxicology (drugs of abuse) screen. * Taking no medication or drugs likely to interfere with the study objectives (including statins or medications that affect hormones \[e.g. birth control pills or steroids\]). * Free of all psychotropic medications (including antidepressants) for at least 6 weeks (with the exception of prn short-acting benzodiazepines or sedative-hypnotics, \< 3 doses per week, and none for 5 drug half-lives before the study). * No vaccines for at least 4 weeks prior to baseline blood draw (including the flu shot). * Not currently anemic (Hct of 36-48 for females and 38-54 for males, or Hgb of 12.5-20) and has not donated blood for at least 8 weeks prior to baseline blood draw. * No neurological disorders and no history of concussion with a black-out that lasted \> 10 minutes. * Willing to provide stool sample Additional criteria for Depressed Participants: * Current DSM-5 diagnosis of Major Depressive Disorder, unipolar, with non-psychotic features. * Baseline 17-item Hamilton Depression Rating Scale (HDRS) rating of \>= 17, or Baseline 25-item HDRS rating of \>= 20. * Current depressive episode duration of \> 6 weeks. * No current, active suicidal intent; HDRS "suicidality" item rating \<= 2 OR by clinician determination. * No recent (\< 6 month) history of substance or alcohol use disorder(s), with the exception of tobacco use (DSM-5 criteria). * No current (in the last month) diagnosis of Post-Traumatic Stress Disorder (DSM-5 criteria). * No anticipated changes in psychotherapeutic interventions during the course of the study. Additional criteria for Normal Controls: • No history of DSM-5 Axis I diagnoses

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143-0984, United States

Location

Related Publications (3)

• Rampersaud R, Wu GWY, Reus VI, Lin J, Blackburn EH, Epel ES, Hough CM, Mellon SH, Wolkowitz OM. Shorter telomere length predicts poor antidepressant response and poorer cardiometabolic indices in major depression. Sci Rep. 2023 Jun 23;13(1):10238. doi: 10.1038/s41598-023-35912-z.

  PMID: 37353495 DERIVED

• Rampersaud R, Protsenko E, Yang R, Reus V, Hammamieh R, Wu GWY, Epel E, Jett M, Gautam A, Mellon SH, Wolkowitz OM. Dimensions of childhood adversity differentially affect biological aging in major depression. Transl Psychiatry. 2022 Oct 4;12(1):431. doi: 10.1038/s41398-022-02198-0.

  PMID: 36195591 DERIVED

• Wolkowitz OM, Mellon SH, Epel ES, Lin J, Reus VI, Rosser R, Burke H, Compagnone M, Nelson JC, Dhabhar FS, Blackburn EH. Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response. Mol Psychiatry. 2012 Feb;17(2):164-72. doi: 10.1038/mp.2010.133. Epub 2011 Jan 18.

  PMID: 21242992 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Owen Wolkowitz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ryan Rampersaud, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2006
• First Posted: February 2, 2006
• Study Start: December 16, 2010
• Primary Completion: August 20, 2025
• Study Completion: August 22, 2025
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)