The goal of this clinical trial is to learn more about decision making in psychosis spectrum disorders, like schizophrenia. Participants will be people who have had symptoms of a psychosis spectrum disorder start within the last five years. The investigators will study how two study agents change decision making in people with psychosis, by asking participants to complete some brain games on the computer before and after taking the study agents. The investigators hope to improve our understanding of psychosis to help people in the future. The main research questions are: * Does a single dose of modafinil change how people with psychosis play the brain games? * Does a single dose of d-serine change how people with psychosis play the brain games? * Does a single dose of modafinil change brain activity? * Does a single dose of d-serine change brain activity? Participants will: * Complete an interview and self-report questionnaires. * Complete safety screening activities, like a blood draw, a urine drug test, and an alcohol breathalyzer test. * Complete functional Magnetic Resonance Imaging (fMRI) scans. fMRI uses magnets to take pictures of the brain. There will be six scanning appointments in the study, with two scans each. Appointments will be about a month apart. * Take a single dose of a study agent during each scanning appointment. The study agent will be taken after the first fMRI. There are three study agents in total: modafinil, d-serine, and a placebo. Each participant will take each study agent twice during the study. * Play brain games on a computer that measure decision making, thinking, and problem solving skills
Participants will be asked to complete ten appointments in this study: An intake appointment, 6 functional Magnetic Resonance Imaging (fMRI) appointments, and 3 clinical interview appointments. In addition, there will be 3 brief clinical check ins, and 6 phone call check ins after fMRI appointments. Intake Appointment: The first appointment is the Intake appointment. This visit will take between 1.75-2.75 hours, depending on how many study tasks are needed. Participants in this study may have participated in a sister study, called "State Representation in Early Psychosis 2 (STEP 2)." If so, they will not need to complete many of the intake questionnaires, and it is expected to take about 100 minutes for them to complete this appointment. If they did not participate in STEP 2, participants will need to complete the full intake battery. During the interview, the investigators will ask questions about a participant's medical and psychiatric history, and current and past mental health symptoms. They will collect demographics, as well as information on the person's social life and quality of life. Participants will also provide a blood sample for clinical safety screening. The investigators will collect one 3mL tube, which is less than 2/3 of a teaspoon. If pregnancy is a physical possibility, they will also collect a urine sample for pregnancy testing. fMRI Appointments: The second appointment is an fMRI + study agent appointment. Participants will come in person to the University of Minnesota Center for Magnetic Resonance Research. This visit will take about 7-7.5 hours. First, the investigators will complete safety screening measures. This will include: * A screening questionnaire to make sure the participant can enter the fMRI machine safely * A blood pressure reading. * A vision test. * A breathalyzer to test for the presence of alcohol. * A urine drug test to screen for the presence of substances. * If pregnancy is a physical possibility, a urine pregnancy test will be required. After screening measures are successfully completed, participants will complete the brain games on a computer. Afterwards, the participant will enter the fMRI machine. The very first fMRI scan will last 2 hours, as the investigators will get additional pictures for the structure of the brain before the scan that measures brain activity. After this, the participant will take a single dose of the study agent. Neither the participant nor the study team will know which study agent the participant is taking. They will be randomly assigned to one of six schedules (for example, one participant will have A \> B \> C, and another will have A \> C \> B, and so on). The participant will be provided with a meal while the study agent metabolizes. Afterwards, the investigators will monitor the participant's vital signs and ask whether they are experiencing any adverse effects. After the observation period is completed, the participant will complete a second fMRI scan. This scan will last 90 minutes. Afterwards, they will play the same brain games on the computer. The investigators will take another vital sign measurement and ask about adverse effects. The following day, the investigators will contact the participant via phone to ask whether they experienced any adverse effects after leaving the study appointment. This call should last about 5 minutes. The remaining 5 fMRI visits will be the same, except that the first scan of the day will be only 90 minutes long. fMRI appointments will be scheduled approximately one month apart. Clinical Interview Appointments: Between fMRIs 1 and 2, 3 and 4, and 5 and 6, the investigators will interview participants to ask questions about their current mental health symptoms, their quality of life, and their social life. Participants will also complete self-report questionnaires which cover the same topics. These appointments will take about 90 minutes. The appointment can be completed in person at the University of Minnesota or remotely via Zoom. Between fMRIs 2 and 3, and 4 and 5, participants will be asked a brief series of questions about their recent mental health symptoms. This will be a remote visit conducted via Zoom or by phone. These calls should take about 20 minutes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
24
Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.
Single dose of oral solution of d-serine, 100 mg/kg. Participants will also receive a placebo capsule to maintain the blind.
Single dose of oral placebo, in both capsule and oral solution
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Baseline
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 7 (fMRI 1)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 36 (fMRI 2)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 63 (fMRI 3)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 91 (fMRI 4)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 119 (fMRI 5)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 147 (fMRI 6)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Baseline
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 7 (fMRI 1)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 36 (fMRI 2)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 63 (fMRI 3)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 91 (fMRI 4)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 119 (fMRI 5)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 147 (fMRI 6)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Baseline
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 7 (fMRI 1)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 36 (fMRI 2)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 63 (fMRI 3)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 91 (fMRI 4)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 119 (fMRI 5)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 147 (fMRI 6)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Baseline
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 7 (fMRI 1)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 36 (fMRI 2)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 63 (fMRI 3)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 91 (fMRI 4)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 119 (fMRI 5)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Time frame: Day 147 (fMRI 6)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 7 (fMRI 1)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 36 (fMRI 2)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 63 (fMRI 3)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 91 (fMRI 4)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 119 (fMRI 5)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Time frame: Day 147 (fMRI 6)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 7 (fMRI 1)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 36 (fMRI 2)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 63 (fMRI 3)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 91 (fMRI 4)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 119 (fMRI 5)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 147 (fMRI 6)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 7 (fMRI 1)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 36 (fMRI 2)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 63 (fMRI 3)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 91 (fMRI 4)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 119 (fMRI 5)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Time frame: Day 147 (fMRI 6)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
Time frame: Baseline
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
Time frame: Day 21 (Clinical A)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
Time frame: Day 49 (Brief Clinical B)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
Time frame: Day 77 (Clinical C)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
Time frame: Day 105 (Brief Clinical D)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Clinician-administered rating scale to assess psychiatric symptoms such as depression, anxiety, hallucinations, and unusual behavior. Scores on individual items range from 1 (not present) to 7 (extremely severe); global scores range from 24 to 168
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Day 133 (Clinical E)
Scale for Assessment of Negative Symptoms/Scale for Assessment of Positive Symptoms (SANS/SAPS) - Global score
The SANS (25 items) and SAPS (34 items) are clinician-administered scales that assess negative and positive symptoms of schizophrenia. Individual items are rated from 0 (symptoms not present) to 5 (Marked symptoms); global scores range from 0 to 295.
Time frame: Day 21 (Clinical A)
Scale for Assessment of Negative Symptoms/Scale for Assessment of Positive Symptoms (SANS/SAPS) - Global score
The SANS (25 items) and SAPS (34 items) are clinician-administered scales that assess negative and positive symptoms of schizophrenia. Individual items are rated from 0 (symptoms not present) to 5 (Marked symptoms); global scores range from 0 to 295.
Time frame: Day 77 (Clinical C)
Scale for Assessment of Negative Symptoms/Scale for Assessment of Positive Symptoms (SANS/SAPS) - Global score
The SANS (25 items) and SAPS (34 items) are clinician-administered scales that assess negative and positive symptoms of schizophrenia. Individual items are rated from 0 (symptoms not present) to 5 (Marked symptoms); global scores range from 0 to 295.
Time frame: Day 133 (Clinical E)