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NCT04951700

Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia

Sponsor: University of Texas Southwestern Medical Center

View on ClinicalTrials.gov

Summary

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.

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

OBSERVATIONAL

Enrollment

194

Start Date

2021-07-01

Completion Date

2027-04-30

Last Updated

2025-08-21

Healthy Volunteers

Yes

Conditions

Schizophrenia Aging Disease Course Biomarker Neuroimaging Cognitive Dysfunction

Interventions

OTHER

Other

This is not an intervention study

Inclusion Criteria: * 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 Exclusion Criteria: • 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) * 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.) * 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 * 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.) * 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.) * History of hypersensitivity to any MRI contrast agent (VASO scan will not be administered. All other imaging modalities are safe to administer.)

Locations (1)

UT Southwestern Medical Center

Dallas, Texas, United States