SchizophreniaNCT04951700
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
An observational study of Schizophrenia and Aging, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Aging, Disease Course
- What is being tested?
- Other
- How many people
- 194 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2021to 28 May 2026
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study population will include individuals with psychotic disorders (schizophrenia or schizoaffective disorder) and healthy comparison participants (individuals without personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st- or 2nd-degree relatives). Participants will be women and men, all races and ethnicities. Participants with schizophrenia/schizoaffective disorder will be aged 18-65 years, healthy comparison participants will be aged 18-75 years.
Who may be able to join
- 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
Who cannot join
- 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]
Show all 11Show fewer
- 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.)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Specific Aims: In order to investigate aging and disease course dimensions in SZ, the study will ascertain a broad panel of biomarkers using multimodal brain imaging, along with comprehensive cognitive and clinical measures, which will allow integration of in vivo molecular; circuit structure and function; and clinical levels of system pathology.
Aim 1. In vivo Molecular Biomarkers. Examine age- and disease course-dependent effects on excitatory and inhibitory 1H-MRS-based biomarkers in the anterior limbic system in SZ. SZ and CON (n=84/group) will undergo novel triple-refocusing 1H-MRS with Glutamate (Glu), GABA and broader metabolite measures from bilateral Hipp and mPFC. Hypothesis 1.1: SZ will show declines in Hipp-mPFC Glu and GABA along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 1.2: SZ will show distinct Hipp-mPFC Glu and GABA markers along the disease course, with significantly elevated or equivalent Glu, and reduced GABA levels, in early SZ, and reduced Glu and GABA in advanced SZ, compared to CON.
Aim 2. Functional Circuit Biomarkers. Examine age- and disease course-dependent effects on intrinsic and task-based activation biomarkers in the anterior limbic circuit in SZ, using high resolution perfusion [Vascular Space Occupancy] and functional MRI with an episodic memory [Pattern Separation] task, respectively. Hypothesis 2.1: SZ will show declines in Hipp-mPFC intrinsic and task-based activity along the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 2.2: SZ will show distinct Hipp-mPFC intrinsic and task-dependent activity signatures across the disease course, with significantly elevated or equivalent regional activation in early SZ, and reduced activation in advanced SZ, compared to CON.
Aim 3. Structural Circuit Biomarkers. Examine age- and disease course-dependent effects on structural biomarkers in the anterior limbic system in SZ, using high resolution structural MRI. Hypothesis 3.1: SZ will show declines in cortical thickness and volume in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced cortical thickness and volume measures in early SZ and larger reductions in advanced SZ, compared to CON.
The investigators also predict that molecular, functional, and structural alterations in the anterior limbic system will be associated with impaired episodic memory and broader cognitive dysfunction in SZ, with declining cognition along both the lifespan and SZ course.
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 the development of relevant precision treatments.
- Conditions
- Schizophrenia, Aging, Disease Course, Biomarker, Neuroimaging, Cognitive Dysfunction
- Being tested
- Other
- Medical subject headings
- Schizophrenia, Disease Progression, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OtherOther
This is not an intervention study
| Study group | Role | What they receive |
|---|---|---|
| Schizophrenia | Women and men, all races and ethnicities, aged 18-65 years, meeting diagnostic DSM-5 criteria for schizophrenia or schizoaffective disorder. Receives: Other: Other | |
| 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. Receives: Other: Other |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
SZ and CON (n=84/group) will undergo novel triple-refocusing Magnetic Resonance Spectroscopy (1H-MRS) with Glutamate, GABA and broader metabolite measures from the anterior limbic system structures (bilateral hippocampi (Hipp) and medial prefrontal cortex (mPFC)), at baseline and 2-year longitudinal follow-up. Hypothesis 1.1: SZ will show declines in Glutamate and GABA in the Hipp and mPFC along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 1.2: SZ will show distinct Hipp-mPFC Glutamate and GABA markers along the disease course, with significantly elevated or equivalent Glutamate, and reduced GABA levels, in early SZ, and reduced Glutamate and GABA in advanced SZ, compared to CON.
Measured: 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).
SZ and CON will undergo high-resolution brain perfusion imaging (VASO) at baseline and 2-year longitudinal follow-up. Hypothesis 2.1: SZ will show declines in Hipp-mPFC CBV along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 2.2: SZ will show distinct Hipp-mPFC CBV signatures across the disease course, with significantly elevated or equivalent CBV in early SZ, and reduced CBV in advanced SZ, compared to CON.
Measured: 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).
SZ and CON will undergo high-resolution brain fMRI with associational memory (Pattern Separation) task at baseline and 2-year longitudinal follow-up. Hypothesis 2.1: SZ will show declines in regional activation (BOLD signal) with Lure>Repetition contrast along the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 2.2: Within the disease course dimension, early SZ will show increased activation with a loss of activation modulation (e.g., increased BOLD signal with both Lures and Repetitions), with a subsequent decline in activation in mid-course and advanced SZ, compared to CON. We predict that these activation effects will be preset in the Hipp DG/CA3 and in a broader circuit supporting pattern separation operations (i.e., mPFC, parahippocampal, retrosplenial cortex).
Measured: 2 years
Effects of aging and disease course on cortical thickness biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).
SZ and CON will undergo high-resolution structural brain MRI, at baseline and 2-year longitudinal follow-up. Hypothesis 3.1: SZ will show declines in FreeSurfer-based cortical thickness in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced cortical thickness in early SZ and larger reductions in advanced SZ, compared to CON.
Measured: 2 years
Effects of aging and disease course on gray matter volume biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).
SZ and CON will undergo high-resolution structural brain MRI, at baseline and 2-year longitudinal follow-up. Hypothesis 3.1: SZ will show declines in gray matter volumes (measured with FreeSurfer and Voxel-Based Morphometry) in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced gray matter volume in early SZ and larger reductions in advanced SZ, compared to CON.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start1 Jul 2021
- Primary completion28 May 2026
- Study completion28 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 194 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Elena Ivleva, University of Texas Southwestern Medical Center
- Investigators
- Elena I. Ivleva, MD, PhD, Principal investigator, UT Southwestern Medical Center, Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04951700
- Sponsor's protocol ID
- STU-2021-0413
- Other IDs
- R01MH127317
- Status last verified
- Oct 2026
- First submitted
- 1 Jun 2021
- Last updated
- 30 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
- ClinicalTrials.gov ID
- NCT04951700
- Acronym / sponsor ID
- STU-2021-0413
- Conditions
- Schizophrenia, Aging, Disease Course, Biomarker, Neuroimaging, Cognitive Dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 28 May 2026 (actual)
- Study completion
- 28 May 2026 (actual)
- First posted
- 7 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Specific Aims: In order to investigate aging and disease course dimensions in SZ, the study will ascertain a broad panel of biomarkers using multimodal brain imaging, along with comprehensive cognitive and clinical measures, which will allow integration of in vivo molecular; circuit structure and function; and clinical levels of system pathology.
Aim 1. In vivo Molecular Biomarkers. Examine age- and disease course-dependent effects on excitatory and inhibitory 1H-MRS-based biomarkers in the anterior limbic system in SZ. SZ and CON (n=84/group) will undergo novel triple-refocusing 1H-MRS with Glutamate (Glu), GABA and broader metabolite measures from bilateral Hipp and mPFC. Hypothesis 1.1: SZ will show declines in Hipp-mPFC Glu and GABA along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 1.2: SZ will show distinct Hipp-mPFC Glu and GABA markers along the disease course, with significantly elevated or equivalent Glu, and reduced GABA levels, in early SZ, and reduced Glu and GABA in advanced SZ, compared to CON.
Aim 2. Functional Circuit Biomarkers. Examine age- and disease course-dependent effects on intrinsic and task-based activation biomarkers in the anterior limbic circuit in SZ, using high resolution perfusion [Vascular Space Occupancy] and functional MRI with an episodic memory [Pattern Separation] task, respectively. Hypothesis 2.1: SZ will show declines in Hipp-mPFC intrinsic and task-based activity along the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 2.2: SZ will show distinct Hipp-mPFC intrinsic and task-dependent activity signatures across the disease course, with significantly elevated or equivalent regional activation in early SZ, and reduced activation in advanced SZ, compared to CON.
Aim 3. Structural Circuit Biomarkers. Examine age- and disease course-dependent effects on structural biomarkers in the anterior limbic system in SZ, using high resolution structural MRI. Hypothesis 3.1: SZ will show declines in cortical thickness and volume in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced cortical thickness and volume measures in early SZ and larger reductions in advanced SZ, compared to CON.
The investigators also predict that molecular, functional, and structural alterations in the anterior limbic system will be associated with impaired episodic memory and broader cognitive dysfunction in SZ, with declining cognition along both the lifespan and SZ course.
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 the development of relevant precision treatments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Schizophrenia | – | Other: OtherWomen and men, all races and ethnicities, aged 18-65 years, meeting diagnostic DSM-5 criteria for schizophrenia or schizoaffective disorder. |
| Healthy Controls | – | Other: OtherWomen 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study population will include individuals with psychotic disorders (schizophrenia or schizoaffective disorder) and healthy comparison participants (individuals without personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st- or 2nd-degree relatives). Participants will be women and men, all races and ethnicities. Participants with schizophrenia/schizoaffective disorder will be aged 18-65 years, healthy comparison participants will be aged 18-75 years.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OtherThis is not an intervention study | Other | Healthy Controls, Schizophrenia |
Primary outcome
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).
Time frame: 2 years
SZ and CON (n=84/group) will undergo novel triple-refocusing Magnetic Resonance Spectroscopy (1H-MRS) with Glutamate, GABA and broader metabolite measures from the anterior limbic system structures (bilateral hippocampi (Hipp) and medial prefrontal cortex (mPFC)), at baseline and 2-year longitudinal follow-up. Hypothesis 1.1: SZ will show declines in Glutamate and GABA in the Hipp and mPFC along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 1.2: SZ will show distinct Hipp-mPFC Glutamate and GABA markers along the disease course, with significantly elevated or equivalent Glutamate, and reduced GABA levels, in early SZ, and reduced Glutamate and GABA in advanced SZ, compared to CON.
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).
Time frame: 2 years
SZ and CON will undergo high-resolution brain perfusion imaging (VASO) at baseline and 2-year longitudinal follow-up. Hypothesis 2.1: SZ will show declines in Hipp-mPFC CBV along the lifespan, with significantly earlier and larger reductions than those observed in CON. Hypothesis 2.2: SZ will show distinct Hipp-mPFC CBV signatures across the disease course, with significantly elevated or equivalent CBV in early SZ, and reduced CBV in advanced SZ, compared to CON.
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).
Time frame: 2 years
SZ and CON will undergo high-resolution brain fMRI with associational memory (Pattern Separation) task at baseline and 2-year longitudinal follow-up. Hypothesis 2.1: SZ will show declines in regional activation (BOLD signal) with Lure>Repetition contrast along the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 2.2: Within the disease course dimension, early SZ will show increased activation with a loss of activation modulation (e.g., increased BOLD signal with both Lures and Repetitions), with a subsequent decline in activation in mid-course and advanced SZ, compared to CON. We predict that these activation effects will be preset in the Hipp DG/CA3 and in a broader circuit supporting pattern separation operations (i.e., mPFC, parahippocampal, retrosplenial cortex).
Effects of aging and disease course on cortical thickness biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).
Time frame: 2 years
SZ and CON will undergo high-resolution structural brain MRI, at baseline and 2-year longitudinal follow-up. Hypothesis 3.1: SZ will show declines in FreeSurfer-based cortical thickness in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced cortical thickness in early SZ and larger reductions in advanced SZ, compared to CON.
Effects of aging and disease course on gray matter volume biomarkers in the anterior limbic system in SZ and CON (Aim3 Outcomes).
Time frame: 2 years
SZ and CON will undergo high-resolution structural brain MRI, at baseline and 2-year longitudinal follow-up. Hypothesis 3.1: SZ will show declines in gray matter volumes (measured with FreeSurfer and Voxel-Based Morphometry) in Hipp, mPFC and broader fronto-temporal regions across the lifespan, with significantly earlier and larger reductions than those in CON. Hypothesis 3.2: SZ will show distinct fronto-temporal alterations along the disease course, with modestly reduced gray matter volume in early SZ and larger reductions in advanced SZ, compared to CON.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena I. Ivleva, MD, PhD principal investigator
UT Southwestern Medical Center, Department of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Schizophrenia and Aging, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.