NCT04951700Completed
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
Source: ClinicalTrials.gov · Last updated 30 Oct 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Completed
- Study type
- Observational
- Enrollment
- 194 (actual)
- First submitted
- 1 Jun 2021
- Start date
- 1 Jul 2021
- Primary completion date
- 28 May 2026
- Lead sponsor
- University of Texas Southwestern Medical Center
- Diseases
- Schizophrenia
- NCT number
- NCT04951700
What you commit to
- Study type: Observational
- Participants enrolled: 194
- From 1 Jul 2021 to the primary completion date, 28 May 2026
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Co-morbid DSM-5 diagnosis of drug/alcohol use disorder in prior 3 months
- Current treatment with benzodiazepine or non-benzodiazepine sedatives/hypnotics, and/or anticonvulsants
Other illness
- Neurological or medical disorder that may affect brain function (history of stroke, head injury with a loss of consciousness \>10 min, seizure disorder, AIDS, poorly controlled hypertension, poorly controlled diabetes, decompensated lung disease, etc.)
- History of hypersensitivity to any MRI contrast agent (VASO scan will not be administered. All other imaging modalities are safe to administer.)
Lab values
- Impaired kidney function: Glomerular Filtration Rate (GFR) \< 30 ml/min/1.73m2 (VASO scan will not be administered due to an association between Gadolinium-based MR contrast use and Nephrogenic Systemic Fibrosis in individuals with severely impaired renal function. All other imaging modalities are safe to administer.)
Age
- Compromised cognitive function: Both SZ and CON participants: Estimated premorbid intellectual ability \<75 age-corrected score on Wide Range Achievement Test-4/Word Reading Subtest (WRAT-4) CON participants: \<26 score on the Montreal Cognitive Assessment (MoCA)
Other
- Presence of ferromagnetic objects in body
- Weight or body size exceeding MRI scanner capacity \[\>300 lbs\]
- Claustrophobia in MRI scanner
- Pregnant women
- Breastfeeding women (VASO scan will not be administered. All other imaging modalities are safe to administer.)
Who the study is looking for
- 18-65 years of age (SZ); 18-75 years of age (CON)
- Women and men
- All races and ethnicities
- Psychiatric diagnoses:
- Patient participants (SZ): Meet DSM-5 criteria for schizophrenia or schizoaffective disorder Healthy control participants (CON): No personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st-or 2nd- degree relatives
- Able to read, speak, and understand English
- Able and willing to provide written informed consent; and willing to commit to the study protocol, including 2-year longitudinal follow-up
Age in the registry: 18 years to 75 years · Sex: All · Accepts healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| UT Southwestern Medical Center Coordinator of this site? Confirm its status | Dallas | United States | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.