Schizophrenia
Conditions
Keywords
Inflammation, Magnetic Resonance Imaging (MRI), Negative Symptoms
Brief summary
This study will recruit persons with schizophrenia or schizoaffective disorder and will use an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation.
Detailed description
Schizophrenia is a severe mental illness that affects 1% of the population, but accounts for over $60 billion in costs to the national healthcare system. Negative symptoms of schizophrenia, including motivational deficits, are some of the most debilitating aspects of the disorder, being both difficult to treat and representing one of the most significant barriers to functional recovery. One pathophysiologic pathway that may contribute to these alterations in reward circuitry in schizophrenia is inflammation. Increased inflammation has been reliably linked to deficits in reward processing and decreased motivation via effects of inflammatory cytokines on regions of the basal ganglia, including the ventral striatum. Previous findings show that some patients with schizophrenia reliably exhibit elevated concentrations of inflammatory markers and that inflammatory cytokines may be related to negative symptoms including decreased motivation. Relevant to the impact of inflammation on insulin signaling, measures of insulin sensitivity are significantly worse in patients with schizophrenia, including at illness onset. Moreover, antipsychotic medications lead to metabolic syndrome, contributing to risk for insulin resistance and ultimately diabetes. Insulin resistance is believed to be caused by increased inflammation, and in turn can contribute to inflammation through alterations in glucose metabolism. This study uses an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation. The researchers will recruit subjects with a range of insulin resistance, as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This will allow the researchers to investigate the contributions of metabolic dysfunction and inflammation on inflammatory and metabolic markers, brain reward circuitry, motivational deficits, and negative symptoms.
Interventions
OTHEROral Glucose Tolerance Test (OGTT)
Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
Sponsors
National Institute of Mental Health (NIMH)
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to give written informed consent * A primary diagnosis of schizophrenia, per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), or schizoaffective disorder as diagnosed by the Mini International Neuropsychiatric Interview (MINI) 7.0 * Mini Mental Status Examination Score ≥24 * Brief Negative Symptom Scale Score ≥25 * No psychotropic medication changes for one month prior to study enrollment; may be taking other psychotropic non-antipsychotic medications (i.e., antidepressants, mood stabilizers, benzodiazepines)
Exclusion criteria
* Evidence of untreated or poorly controlled endocrine, thyroid, cardiovascular, hematological, renal, neurological disease, hepatitis B or C or HIV * Current HbA1C ≥ 8.5% * Prior treatment with antiviral or immunomodulatory drugs, including corticosteroids within six months of study entry * Current treatment with antibiotics * Primary diagnosis of major depressive disorder or bipolar disorder * Active abuse of alcohol or illicit/prescription drugs within the past 6 months including a urine toxicology screen positive for drugs of abuse (patients may still be included with a positive tetrahydrocannabinol (THC) result at the discretion of the PI) * Predominant left-handedness excluded for portions of the MRI scan * Wide Range Achievement Test-3 Reading Scale (WRAT-3) score indicating less than 8th grade reading level, unless otherwise approved by the PI or PI's designee * Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol * History of central nervous system trauma or active seizure disorder requiring medication * Positive pregnancy test * Presence of metal in the body (excludes from MRI scan only) * Active suicidal ideation as determined by the PI and/or study staff * Diagnosis of diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effort-Expenditure for Rewards Task (EEfRT) Score | Baseline, Hour 1 | EEfRT is a multitrial game task assessing motivation in which participants choose between 2 different task difficulty levels to obtain monetary rewards. For all trials, participants make repeated manual button presses which raises the level of a virtual ''bar'' viewed onscreen by the participant. Participants are eligible to win the money allotted for each trial if they raise the bar to the ''top''. Each trial presents subjects with a choice between 'high effort' and 'low effort' tasks that require different amounts of button pressing. Reward magnitudes for the high-effort task vary between amounts, while reward magnitudes for the low-effort task remain constant. Trials also vary in terms of 3 levels of probability of winning the amount associated with the choice selected. The first 50 trials are used for analysis. Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Finger Tapping Task (FTT) Score | Baseline, Hour 1 | The Finger Tapping Task (FTT) uses a specially adapted tapper that the subject is asked to tap as fast as possible. The subject is given 5 consecutive 10-second trials for the preferred and non-preferred hands.The FTT is design to assess subtle motor impairment and found to be altered in subjects with basal ganglia disorders and lesions. The finger tapping score is the mean number of taps of 5 trials and is computed for each hand. |
| Trail Making Test Part A (TMT-A) Score | Baseline, Hour 1 | The Trail Making Test-A is a timed task that provides information on motor function and speed of processing. In Part A of the TMT participants connect circles labeled with numbers, in ascending order. The score is the amount of time it takes for the participant to complete the task. The average time it takes to complete the task is 29 seconds and times longer than 78 seconds suggest a deficiency. |
| Digit Symbol Substitution Task (DSST) Score | Baseline, Hour 1 | The DSST is a subtest of the Wechsler Adult Intelligence Scale and involves graphimotor speed, visual scanning and memory, with about half of the variance being accounted for by graphimotor speed, a third by visual scanning and 4-5% by memory. Performance on the Digit Symbol Test has been found to correlate with subcortical (caudate) atrophy in disorders involving the basal ganglia. Respondents match symbols to numbers using a key presented at the top of the test page. The score is the number of correctly entered symbols in the given time period and higher scores indicate better performance. |
| Profile of Mood States (POMS) Brief Score | Baseline, Hour 1 | The POMS is a 30-item rating scale designed to measure mood states across short periods. The POMS assess six mood factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Each item is rated on a 5-point scale where 0 = not at all and 4 = extremely. Total scores range from 0 to 120 and lower scores indicate a better state of mood. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma C-reactive Protein (CRP) Levels | Baseline, Hours 1, 2, and 3 | Plasma CRP will be assessed to determine the impact of insulin resistance on inflammatory markers. |
| Change in Monocyte Chemoattractant Protein-1 (MCP-1) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. MCP-1 levels before and after the OGTT will be examined. |
| Change in Interleukin-10 (IL-10) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-10 levels before and after the OGTT will be examined. |
| Change in Soluble Interleukin-6 Receptor (sIL-6R) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sIL-6R levels before and after the OGTT will be examined. |
| Change in Interleukin-6 (IL-6) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-6 levels before and after the OGTT will be examined. |
| Fasting Blood Glucose | Baseline, Hours 1, 2, and 3 | Fasting blood glucose will be assessed to determine the impact of insulin resistance on inflammatory markers. |
| Change in Interleukin-1beta (IL-1beta) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1beta levels before and after the OGTT will be examined. |
| Change in Interleukin-1 Receptor Antagonist (IL-1RA) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1RA levels before and after the OGTT will be examined. |
| Change in Tumor Necrosis Factor (TNF)-Alpha Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MultiAnalyte Profiling (MAP) Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. TNF-alpha levels before and after the OGTT will be examined. |
| Change in Resting State Scan | Baseline, Hour 3 | For the resting state and task-based functional connectivity analysis, whole brain, subject-level correlation maps indicating regional similarity with the striatal seed region time series will be generated and Fisher transformed to Z-score maps. In addition, data reduction strategies will be employed to address inflammatory marker collinearity in analyses combining relevant inflammatory markers. To assess the significance of correlated activity with each bilateral seed region, paired t-tests will be conducted on participants' Z-score maps, adjusted for multiple comparisons. For significant brain regions, descriptive statistics will be used to characterize the mean, standard deviation, and standard error of the Z scores. |
| Change in Soluble TNF Receptor 2 (sTNFR2) Levels | Baseline, Hours 1, 2, and 3 | Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sTNFR2 levels before and after the OGTT will be examined. |
| Fasting Blood Insulin | Baseline, Hours 1, 2, and 3 | Fasting blood insulin will be assessed to determine the impact of insulin resistance on inflammatory markers. |
| Neural Response to Reward Motivation Assessed by fMRI-adapted Version of the EEfRT | Baseline, Hour 3 | Assessment of effort-based decision-making will be made using the EEfRT task adapted for fMRI. During each trial, subjects are presented with a choice between two levels of task difficulty, a High Effort option, and a Low Effort option. Unlike in the behavioral version of the task, subjects will not be required to make button presses during the scan. The reward magnitude for a No Effort option remains constant, while the reward magnitude for the High Effort option varies. Additionally, the amount of effort required for the High Effort option will vary between 20%, 50%, 80%, and 100% of the subject's maximum effort (set for each individual before the scan). |
| Change in Neural Response to Anticipating and Receiving Monetary Rewards Assessed by Monetary Incentive Delay (MID) Task | Baseline, Hour 3 | Assessment of reward anticipation will be achieved using the MID task, conducted during functional MRI (fMRI) neuroimaging. Briefly, during this task participants have the opportunity to win or lose money by making a rapid button press in response to a target visual stimulus. The primary epoch of interest is the anticipatory delay - a period of \ 2000ms that occurs after participants have been informed how much money they can win or lose on a given trial, but prior to the presentation of the target. This epoch has repeatedly been associated with robust ventral striatal activity. Participants will complete 2 functional runs of between 50 and 200 trials each (the number of trials will be decided at the discretion of the PI), with evenly distributed reward magnitudes. |
| Change in Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time Score | Baseline, Hour 1 | This reaction time test includes simple and choice reaction time tasks and is divided into 5 stages requiring increasingly complex chains of responses and providing a distinction between reaction (or decision) time and movement latencies. Movement times on the CANTAB reaction time task have been slowed during interferon-alpha (IFN-α) treatment and correlated with IFN-alpha-induced depression and fatigue. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Grady Health System in Atlanta, Georgia, USA. Participant enrollment began August 31, 2020, and all follow-up was complete by March 1, 2022.
Pre-assignment details
This was an optional substudy underpowered to identify relationships between changes in inflammatory and metabolic markers pre- and post-OGTT with reward circuitry or motivational deficits. These analyses are thus exploratory and would serve as preliminary data for future research proposals.
Participants by arm
| Arm | Count |
|---|---|
| Oral Glucose Tolerance Test (OGTT) Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Exclusion due to positive UDS (THC) test | 1 |
Baseline characteristics
| Characteristic | Oral Glucose Tolerance Test (OGTT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 35.36 years STANDARD_DEVIATION 12.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Effort-Expenditure for Rewards Task (EEfRT) Score
EEfRT is a multitrial game task assessing motivation in which participants choose between 2 different task difficulty levels to obtain monetary rewards. For all trials, participants make repeated manual button presses which raises the level of a virtual ''bar'' viewed onscreen by the participant. Participants are eligible to win the money allotted for each trial if they raise the bar to the ''top''. Each trial presents subjects with a choice between 'high effort' and 'low effort' tasks that require different amounts of button pressing. Reward magnitudes for the high-effort task vary between amounts, while reward magnitudes for the low-effort task remain constant. Trials also vary in terms of 3 levels of probability of winning the amount associated with the choice selected. The first 50 trials are used for analysis. Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation.
Time frame: Baseline, Hour 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Effort-Expenditure for Rewards Task (EEfRT) Score | Baseline | 0.268 proportion of hard-task choices | Standard Deviation 0.217 |
| Oral Glucose Tolerance Test (OGTT) | Effort-Expenditure for Rewards Task (EEfRT) Score | Hour 1 | 0.189 proportion of hard-task choices | Standard Deviation 0.153 |
Secondary
Digit Symbol Substitution Task (DSST) Score
The DSST is a subtest of the Wechsler Adult Intelligence Scale and involves graphimotor speed, visual scanning and memory, with about half of the variance being accounted for by graphimotor speed, a third by visual scanning and 4-5% by memory. Performance on the Digit Symbol Test has been found to correlate with subcortical (caudate) atrophy in disorders involving the basal ganglia. Respondents match symbols to numbers using a key presented at the top of the test page. The score is the number of correctly entered symbols in the given time period and higher scores indicate better performance.
Time frame: Baseline, Hour 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Digit Symbol Substitution Task (DSST) Score | Baseline | 60.55 Number of correct entered symbols | Standard Deviation 20.28 |
| Oral Glucose Tolerance Test (OGTT) | Digit Symbol Substitution Task (DSST) Score | Hour 1 | 55.09 Number of correct entered symbols | Standard Deviation 20.98 |
Secondary
Finger Tapping Task (FTT) Score
The Finger Tapping Task (FTT) uses a specially adapted tapper that the subject is asked to tap as fast as possible. The subject is given 5 consecutive 10-second trials for the preferred and non-preferred hands.The FTT is design to assess subtle motor impairment and found to be altered in subjects with basal ganglia disorders and lesions. The finger tapping score is the mean number of taps of 5 trials and is computed for each hand.
Time frame: Baseline, Hour 1
Population: 11 participants analyzed for baseline, but only 10 completed the 1-hour measurements. One participant could not complete the tasks for the left hand.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Finger Tapping Task (FTT) Score | Right Hand Baseline | 44.22 number of taps on a 10 second counter | Standard Deviation 6.74 |
| Oral Glucose Tolerance Test (OGTT) | Finger Tapping Task (FTT) Score | Right Hand- Hour 1 | 42.68 number of taps on a 10 second counter | Standard Deviation 11.44 |
| Oral Glucose Tolerance Test (OGTT) | Finger Tapping Task (FTT) Score | Left hand Baseline | 39.98 number of taps on a 10 second counter | Standard Deviation 10.91 |
| Oral Glucose Tolerance Test (OGTT) | Finger Tapping Task (FTT) Score | Left hand- Hour 1 | 42.01 number of taps on a 10 second counter | Standard Deviation 6.4 |
Secondary
Profile of Mood States (POMS) Brief Score
The POMS is a 30-item rating scale designed to measure mood states across short periods. The POMS assess six mood factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Each item is rated on a 5-point scale where 0 = not at all and 4 = extremely. Total scores range from 0 to 120 and lower scores indicate a better state of mood.
Time frame: Baseline, Hour 1
Population: Only participants with available data are included in the analysis. Baseline data was inadvertently lost and only available for two (2) participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Profile of Mood States (POMS) Brief Score | Baseline | 37.50 Score on a scale | Standard Deviation 37.48 |
| Oral Glucose Tolerance Test (OGTT) | Profile of Mood States (POMS) Brief Score | 1 hour post | 20.27 Score on a scale | Standard Deviation 12.36 |
Secondary
Trail Making Test Part A (TMT-A) Score
The Trail Making Test-A is a timed task that provides information on motor function and speed of processing. In Part A of the TMT participants connect circles labeled with numbers, in ascending order. The score is the amount of time it takes for the participant to complete the task. The average time it takes to complete the task is 29 seconds and times longer than 78 seconds suggest a deficiency.
Time frame: Baseline, Hour 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Trail Making Test Part A (TMT-A) Score | Baseline | 38.86 Seconds | Standard Deviation 15.44 |
| Oral Glucose Tolerance Test (OGTT) | Trail Making Test Part A (TMT-A) Score | Hour 1 | 37.02 Seconds | Standard Deviation 16.12 |
Other Pre-specified
Change in Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time Score
This reaction time test includes simple and choice reaction time tasks and is divided into 5 stages requiring increasingly complex chains of responses and providing a distinction between reaction (or decision) time and movement latencies. Movement times on the CANTAB reaction time task have been slowed during interferon-alpha (IFN-α) treatment and correlated with IFN-alpha-induced depression and fatigue.
Time frame: Baseline, Hour 1
Other Pre-specified
Change in Interleukin-10 (IL-10) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-10 levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Interleukin-1beta (IL-1beta) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1beta levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Interleukin-1 Receptor Antagonist (IL-1RA) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1RA levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Interleukin-6 (IL-6) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-6 levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Monocyte Chemoattractant Protein-1 (MCP-1) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. MCP-1 levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Neural Response to Anticipating and Receiving Monetary Rewards Assessed by Monetary Incentive Delay (MID) Task
Assessment of reward anticipation will be achieved using the MID task, conducted during functional MRI (fMRI) neuroimaging. Briefly, during this task participants have the opportunity to win or lose money by making a rapid button press in response to a target visual stimulus. The primary epoch of interest is the anticipatory delay - a period of \ 2000ms that occurs after participants have been informed how much money they can win or lose on a given trial, but prior to the presentation of the target. This epoch has repeatedly been associated with robust ventral striatal activity. Participants will complete 2 functional runs of between 50 and 200 trials each (the number of trials will be decided at the discretion of the PI), with evenly distributed reward magnitudes.
Time frame: Baseline, Hour 3
Other Pre-specified
Change in Resting State Scan
For the resting state and task-based functional connectivity analysis, whole brain, subject-level correlation maps indicating regional similarity with the striatal seed region time series will be generated and Fisher transformed to Z-score maps. In addition, data reduction strategies will be employed to address inflammatory marker collinearity in analyses combining relevant inflammatory markers. To assess the significance of correlated activity with each bilateral seed region, paired t-tests will be conducted on participants' Z-score maps, adjusted for multiple comparisons. For significant brain regions, descriptive statistics will be used to characterize the mean, standard deviation, and standard error of the Z scores.
Time frame: Baseline, Hour 3
Other Pre-specified
Change in Soluble Interleukin-6 Receptor (sIL-6R) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sIL-6R levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Soluble TNF Receptor 2 (sTNFR2) Levels
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sTNFR2 levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Change in Tumor Necrosis Factor (TNF)-Alpha Levels
Fluorokine MultiAnalyte Profiling (MAP) Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. TNF-alpha levels before and after the OGTT will be examined.
Time frame: Baseline, Hours 1, 2, and 3
Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Other Pre-specified
Fasting Blood Glucose
Fasting blood glucose will be assessed to determine the impact of insulin resistance on inflammatory markers.
Time frame: Baseline, Hours 1, 2, and 3
Population: Only baseline values were analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Fasting Blood Glucose | 94.27 mg/dL | Standard Deviation 18.78 |
Other Pre-specified
Fasting Blood Insulin
Fasting blood insulin will be assessed to determine the impact of insulin resistance on inflammatory markers.
Time frame: Baseline, Hours 1, 2, and 3
Population: Only baseline values were analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Fasting Blood Insulin | 12.9 mIU/L | Standard Deviation 10.05 |
Other Pre-specified
Neural Response to Reward Motivation Assessed by fMRI-adapted Version of the EEfRT
Assessment of effort-based decision-making will be made using the EEfRT task adapted for fMRI. During each trial, subjects are presented with a choice between two levels of task difficulty, a High Effort option, and a Low Effort option. Unlike in the behavioral version of the task, subjects will not be required to make button presses during the scan. The reward magnitude for a No Effort option remains constant, while the reward magnitude for the High Effort option varies. Additionally, the amount of effort required for the High Effort option will vary between 20%, 50%, 80%, and 100% of the subject's maximum effort (set for each individual before the scan).
Time frame: Baseline, Hour 3
Other Pre-specified
Plasma C-reactive Protein (CRP) Levels
Plasma CRP will be assessed to determine the impact of insulin resistance on inflammatory markers.
Time frame: Baseline, Hours 1, 2, and 3
Population: One participant did not get CRP drawn. Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Plasma C-reactive Protein (CRP) Levels | 3.83 mg/L | Standard Deviation 4.67 |