NCT04951700

Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia

StatusCompleted

PhaseNot specified

SponsorUniversity of Texas Southwestern Medical Center

Primary completionMay 28, 2026

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Record History

All 7 versions: 6 with changes below, 1 re-verified with no change. See every version on ClinicalTrials.gov ↗

Minor Oct 28, 2026 Trial completed
- Study completion date changed from estimate of Apr 30, 2027 to May 28, 2026
- Eligibility criteria shortened, about 12 words
- Study description revised
Minor Aug 15, 2025 Trial status: Recruiting to Active, Not Recruiting
- Enrollment target: estimated 168 to confirmed 194
- Site details revised
v6
Minor Aug 13, 2024 Collaborators expanded, about 6 wordsv5
Minor Jul 19, 2022 Primary completion date: Jun 30, 2026 to Apr 30, 2026
- Study completion date: Jun 30, 2026 to Apr 30, 2027
v3
Notable Jul 12, 2021 Trial status: Not Yet Recruiting to Recruiting
- Site details revised
- Study description expanded, about 1 word
v2
Jun 24, 2021 Study First Submitted

Notable: the plan changed
Minor: routine updates

Endpoints

Primary

Effects of aging and disease course on excitatory and inhibitory biomarkers in the anterior limbic system in schizophrenia (SZ) and healthy controls (CON) (Aim1 Outcomes).

Timeframe: 2 years

Effects of aging and disease course on intrinsic activity biomarkers [VASO-based Cerebral Blood Volume (CBV)] in the anterior limbic circuit in SZ and CON (Aim2 Outcome).

Timeframe: 2 years

Effects of aging and disease course on memory task-driven activation biomarkers [fMRI with Pattern Separation task] in the anterior limbic circuit in SZ and CON (Aim2 Outcome).

Timeframe: 2 years

Effects of aging and disease course on cortical thickness biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).

Timeframe: 2 years

Effects of aging and disease course on gray matter volume biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).

Timeframe: 2 years

Arms and interventions

Schizophrenia

Women and men, all races and ethnicities, aged 18-65 years, meeting diagnostic DSM-5 criteria for schizophrenia or schizoaffective disorder.

Healthy Controls

Women and men, all races and ethnicities, aged 18-75 years, without personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st- or 2nd-degree relatives.

Other: Other

Sites

1 site in 1 country

UT Southwestern Medical CenterDallas, Texas, United States

About this trial

The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However, their clinical correlates, associated biomarker trajectories, and implications for treatment are unknown. This study will investigate differential aspects of SZ neurobiology captured by aging and disease course, in order to develop specific biomarkers which may offer actionable targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints within the anterior limbic system for aging and disease course in SZ: (1) alterations in the circuit's function and structure that occur earlier in the lifespan and are larger in magnitude than the alterations expected with normal aging (accelerated aging dimension); and (2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will ascertain a broad panel of biomarkers \[via multimodal brain imaging: optimized 1H-MRS, high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI\], along with comprehensive cognitive and clinical assessments. All measures will be acquired at baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational approaches, the study will examine (i) effects of aging and SZ course on anterior limbic system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older, Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs. without accelerated aging profiles); and (iv) associations between biomarkers and cognitive and clinical outcomes. This research will advance the field by providing novel biomarkers that capture unique neurobiological contributions of aging and disease course in SZ, and will motivate future studies on SZ mechanisms across the lifespan and development of precision treatments.

Trial details

Enrollment: 194 participants (actual)
Started: Jul 1, 2021
Study completion: May 28, 2026
Eligibility: 18 to 75, all sexes, healthy volunteers accepted
Design: Observational
Conditions: Cognitive Dysfunction, Disease Progression, Schizophrenia, Aging, Disease Course, Biomarker, Neuroimaging
Collaborators: National Institute of Mental Health (NIMH)
First posted: Jul 7, 2021
Registry updated: Oct 30, 2026
Last verified: Oct 2026

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