Clinical trial NCT05273164: State Representation in Early Psychosis
Official title: State Representation in Early Psychosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Psychosis
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Schizoaffective Disorder
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-03-10
Enrollment: 350
Sex: ALL
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to examine state representation in individuals aged 15-45 who have been diagnosed with a psychotic illness, as well as young adults who do not have a psychiatric diagnosis. State Representation is our ability to process information about our surroundings. The investigators will complete some observational tests as well as a cognitive training clinical trial.

Detailed description: In the first component of this study, participants will be asked to complete two sets of appointments six months apart. During both sets of appointments, participants will be asked to complete interviews examining behaviors and symptoms of mental health conditions, self-report questionnaires, and a neurocognitive assessment. In addition, participants will complete an imaging appointment, in which they will receive simultaneous EEG and fMRI while performing two computerized tasks.

The purpose of this component is to determine how failures in information processing that support state representation in neural circuits relate to clinical heterogeneity in early psychosis. To this end, the investigators will: (a) Recruit people with early psychosis and demographically similar adults without a psychiatric illness aged 15-45 years; (b) Determine test-retest reliability of variants of the DPX and Bandit tasks as assessments of state representation processes; (c) Characterize behavioral performance and neurophysiology at baseline using the DPX and Bandit task variants during simultaneous EEG-fMRI along with other MRI modalities; (d) Follow patients for 6 months while they receive usual care, to delineate their clinical trajectories; (e) Repeat the behavioral and EEG-fMRI assessments after six months. The data the investigators acquire will allow us to examine the baseline relationships between clinical and experimental measures, and also to investigate how changes in clinical and experimental measures are related over a 6-month time period during a critical phase of illness.

In the second component of this study, participants will be invited to enroll in a clinical trial examining two forms of computerized cognitive training. They will be asked to complete 10 hours of training over a 3-6 week period. Upon completion of the training paradigm, they will have two additional follow up visits, a post-intervention and a 5 month follow up (which will correspond to approximately 12 months from enrollment). At both of these appointments, participants will complete the same activities completed in the first component of this project, including the interviews, questionnaires, neurocognitive assessment, and imaging combined with computerized tasks.

In the second component, the investigators will recruit adults with early psychosis and demographically matched individuals without a mental health diagnosis who have completed the first component of the research. Participants will be stratified on an EEG index of state estimation processes (fronto-parietal theta power at encoding) and randomly assigned to the two training paradigms. The investigators will investigate parameter changes in the fit causal discovery analyses in each group, fit to DPX and Bandit task variant behavioral data immediately after training and 5 months later, and they will assess whether parameter changes reflect restorative or compensatory modifications. Finally, the investigators will test the hypothesis that state representation processes and cognitive performance show greater improvement in subjects who received training tailored to their state estimation parameter.

Eligibility criteria: Inclusion Criteria:

* English proficiency, as determined by staff observation and participant self-report
* Estimated IQ at or above 70, as estimated by the cognitive assessments

Additional Inclusion Criteria for Early Psychosis Participants:

* Clinical diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, psychosis NOS, bipolar disorder with psychosis, or major depressive disorder with psychosis; those aged 36-45 years old must have had with onset of psychotic symptoms within the previous 5 years
* Achieved clinical stability, defined as outpatient status for at least one month prior to study participation

Exclusion Criteria:

* Unable or unwilling to provide informed consent
* The participant is unable to demonstrate adequate decisional capacity, in the judgment of the consenting study staff member, to make a choice about participating in the research study
* Participant is pregnant
* Participant is illiterate
* Cannot pass the CMRR Subject Safety Screen due to MRI contraindications
* Presence of a major neurological disorder
* Previous clinically significant head injury or prolonged unconsciousness, as determined by the PI/Co-Is
* Meets criteria for substance or alcohol dependence within 3 months of enrollment
* The presence of any major medical condition that, in the opinion of the PI/Co-Is, would impede participation in the study or would put the participant at additional risk by participating
* Presence of severe alcohol or substance abuse

Additional Exclusion Criteria for Early Psychosis Participants:

* Has participated in significant formal cognitive training programs, as determined by the PI/Co-Is
* Meets criteria for clinical risk of suicidal behavior, as defined by:
* Clinician judgement
* A suicide attempt within 6 months of enrollment
* Active suicidal ideation at screening or baseline, as indicated by the C-SSRS
* Previous intent to act on suicidal ideation with a specific plan and/or preparatory acts within 6 months of enrollment, as indicated by the C-SSRS

Additional Exclusion Criteria for Control Participants:

* Meets DSM-5 criteria for psychotic, bipolar, or autism spectrum disorder
* Has a family history (1st degree relative) of psychotic, bipolar, or autism spectrum disorder

Primary outcomes:
measure: Change in Performance of DPX Task Variant
timeFrame: Baseline, 6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Performance of Bandit Task Variant
timeFrame: Baseline, 6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Test My Brain Neurocognitive Assessment performance: Global Cognition Z Score.
timeFrame: Baseline, 6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in EEG Variables
timeFrame: Baseline, 6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in MRI Variables
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
Secondary outcomes:
measure: Change in symptoms and functioning as indicated by Minnesota Symptom Severity Scale
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the SANS/SAPS
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the BPRS
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the SPQ-BR
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the SGI
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the IDI
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the WHODAS 2.0 Brief
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in symptoms and functioning as indicated by the GFS/GFR
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Test My Brain Neurocognitive Assessment performance: Digit Symbol Matching Z Score
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Test My Brain Neurocognitive Assessment performance: Verbal Pair Associates Memory Z Score
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Test My Brain Neurocognitive Assessment performance: Matrix Reasoning Z Score
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
measure: Change in Test My Brain Neurocognitive Assessment performance: Multiracial Emotion Identification Z Score
timeFrame: Baseline,6 month follow up, Immediately after the intervention, 12 month follow up
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Sophia Vinogradov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Angus MacDonald III, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: