Schizophrenia
Conditions
Keywords
Schizophrenia, Schizoaffective Disorder, Mental Disorders, Anti-Dyskinesia Agents, Antiparkinson Agents, Central Nervous System Agents, Dopamine Agents, Excitatory Amino Acid Agents, Excitatory Amino Acid Antagonists, Molecular Mechanisms of Pharmacological Action, Neurotransmitter Agents, Pharmacologic Actions, Physiological Effects of Drugs, Therapeutic Uses, Prepulse inhibition, Neurocognition, Working memory, Dextroamphetamine, MATRICS Consensus Cognitive Battery, Pharmacologic Augmentation of Cognitive Therapies, Sensory discrimination learning, Targeted Cognitive Training, rs4680 polymorphism of catechol-O-methyltransferase (COMT)
Brief summary
This application seeks renewed support for MH59803, Dopaminergic substrates of startle gating across species, to extend a clear path of bench-to-bedside progress towards a critical paradigm shift in therapeutic models for schizophrenia (SZ) and schizoaffective disorder, depressed type (SZA): the use of Pharmacologic Augmentation of Cognitive Therapies (PACTs). This novel therapeutic strategy for SZ/SZA directly addresses the need for more effective treatments for this devastating disorder. MH59803 has investigated the neural regulation of laboratory-based measures of deficient information processing in SZ/SZA patients, using rodents and healthy human subjects (HS) to explicate the biology of these deficits, and to establish a rational basis for developing novel therapies for SZ/SZA. In its first 9 years, MH59803 studies of the neural regulation of prepulse inhibition (PPI) of startle in rats focused on basic neurobiological and molecular mechanisms. Over the past 2 years of support, MH59803 studies moved from bench-to-bedside, focusing on dopamine (DA) agonist effects on PPI and neurocognition in HS, and their regulation by genes identified in cross-species studies. These studies detected biological markers that predict PPI-enhancing and pro-cognitive effects of the DA releaser, amphetamine (AMPH) in humans, leading to specific predictions of AMPH effects on PPI, neurocognition and Targeted Cognitive Training in SZ/SZA patients. If confirmed in the present application, these predictions could help transform therapeutic approaches to SZ/SZA. This renewal application of MH59803 thus reflects a logical progression of studies at systems and molecular levels, translated first to HS, and now to potentially transformative therapeutic models in SZ/SZA patients.
Detailed description
MH59803 demonstrated that AMPH (20 mg p.o.) significantly increased PPI and neurocognitive performance (MATRICS Consensus Cognitive Battery; MCCB) in HS characterized by specific performance-based or genetic biomarkers, including the val/val genotype for the rs4680 polymorphism of catechol-O-methyltransferase (COMT). Mechanistically-informative results were detected in studies of AMPH effects on PPI in rats with high vs. low brain regional Comt expression. Together with several reports of improved neurocognition and no adverse effects of acute or sustained AMPH administration to antipsychotic (AP)-medicated SZ/SZA patients, MH59803 findings provide a strong rationale for the next goal of this application: to test the potential utility of AMPH in a paradigm of biomarker-informed PACTs. This next step is highly innovative - never previously reported, or perhaps even attempted - and consistent with National Institute of Mental Health (NIMH) objectives, directly challenges existing models for SZ/SZA therapeutics. Investigators will determine whether a test dose of 10 mg AMPH p.o. administered to biomarker-identified, AP-medicated SZ/SZA patients generates predicted increases in PPI, MCCB performance, and sensory discrimination learning in a Targeted Cognitive Training (TCT) module. In total, Investigators will leverage knowledge generated through converging cross-species studies in MH59803, to directly advance scientific and clinical domains, by testing the effects of a pro-cognitive drug on neurophysiological and neurocognitive performance, and Targeted Cognitive Training, in biomarker-stratified subgroups of SZ/SZA patients. Aim: To assess acute effects of AMPH (0 vs 10 mg po) on PPI, neurocognition and computerized TCT in AP-medicated SZ/SZA patients. Hypothesis: PPI- and MCCB-enhancing effects of AMPH seen previously in HS will also be detected in SZ/SZA patients, as will TCT-enhancing effects of AMPH. Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism. Concurrent HS testing will confirm and extend findings of AMPH effects on PPI and neurocognition, and help interpret findings in SZ/SZA patients. In all participants, the aim to assess acute effects of 0 vs. 10 mg po dextroamphetamine (AMPH) on Prepulse Inhibition (PPI), neurocognition MATRICS: Consensus Cognitive Battery; MCCB, and computerized Targeted Cognitive Training (TCT). Hypothesis: AMPH will enhance: 1. PPI 2. neurocognition (MCCB performance) 3. computerized TCT performance in biomarker-identified SZ/SZA patients. 4. The PPI and MCCB-enhancing effects of AMPH seen previously in HS will also be detected in SZ/SZA patients, as will TCT-enhancing effects of AMPH. Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism. Concurrent HS testing will confirm and extend findings of AMPH effects on PPI and neurocognition, and help interpret findings in SZ/SZA patients.
Interventions
Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
DRUGPlacebo
Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-55 years old: * Drug Free (No recreational/street drugs) * Diagnosis of Schizophrenia or Schizoaffective Disorder, Depressed Type * Must be stable on antipsychotic medication for at least 1 month * Any medications other than antipsychotic medications need to be stable for at least 1 week
Exclusion criteria
* Dominant hand injury * Hearing impairment at 40 dB * Irregular menstrual cycle or cycle is no within in 25-35 days (menopausal is eligible) * EKG, conduction abnormalities confirmed by cardiologist * Reading component of Wide Range Achievement Test 4 (WRAT4) Score less than 70 * Any serious illness, including: Insulin-dependent diabetes, HIV, AIDS, cancer, stroke, heart attack, uncontrolled hypothyroidism * Sleep apnea * A diagnosis of epilepsy or history of seizures with loss of consciousness * Open/closed head injury with loss of consciousness greater than 1 minute at any time in the lifetime * Blood pressure: Systolic Blood Pressure \< 90 or \> 160, Diastolic Blood Pressure \< 45 or \> 95 * Heart Rate \< 55 or \> 110 * Current use of Dexatrim or drugs containing phenylephrine (eligible if not used for at least 72 hours prior to participation) * Current use of St. John's Wort, Milk Thistle (eligible if for at least 1 month) * Self report of any illicit drug use within the last 30 days * Positive urine toxicology * Self-report of any use of ecstasy, lysergic acid diethylamide (LSD), mushrooms, gamma hydroxybutyrate (GHB), ketamine, phencyclidine (PCP), heroin or any intravenous-drugs within past year * If there is a history of substance abuse/addiction, participant must be in remission for at least 6 months * Within 1 month of recent psychiatric hospitalization * Current mania * Dementia/Alzheimer's diagnosis * Mania episode meeting criteria outlined in the MINI-International Neuropsychiatric Interview Plus 6.0 (M.I.N.I. plus 6.0) anytime in the lifetime (hypomania/Bipolar II eligible)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prepulse Inhibition (PPI) | two visits, 1 week apart, each visit lasting approximately 6 hours | PPI was assessed with 42 trials of 6 types: 118 dB 40 ms pulse alone (P) & the same P preceded 10, 20, 30, 60, or 120 ms by a prepulse (pp) 16 dB over background. Startle magnitude (SM), habituation, latency & latency facilitation were measured to interpret changes in PPI. %PPI = 100 x \[(SM on P trials) - (SM on pp+P trials)\] / SM on P trials. Example: SM on P trials = 80 units SM on pp+P trials = 30 units %PPI = 100 x (80-30)/80 = 100 x 50/80 = 62.5% Greater %PPI mean the reflex has been inhibited to a greater extent in the presence of a pp. %PPI can't exceed 100: when SM on pp+P trials = 0, then %PPI = 100 x (SM on P trials - 0)/SM on P trials = 100 x 1 = 100%. However, %PPI can theoretically be infinitely negative since SM on pp+P trials could be infinitely large (prepulse facilitiation (PPF)), i.e. SM is potentiated in the presence of a pp. PPF is normal at very short & very long pp intervals, but not within a species-specific physiological range of intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MATRICS Consensus Cognitive Battery Performance (MCCB) | two visits, 1 week apart, each visit lasting approximately 6 hours | The T-score indicates the performance on a neurocognitive battery of tests. Higher score reflects better performance. |
| Targeted Cognitive Training (TCT): PositScience, Inc. | two visits, 1 week apart, each visit lasting approximately 6 hours | Auditory discrimination learning: Subjects identify direction (up vs. down) of 2 consecutive sound sweeps. Parameters (e.g. inter-sweep interval, sweep duration) are established for subjects to maintain 80% correct responses. On screen and test days, subjects complete 1h of TCT. Analytic software yields the key measures: auditory processing speed (APS) and APS learning. APS is the shortest inter-stimulus interval at which a subject performs to criteria and APS learning is the difference (ms) between the first APS and the best APS of the subsequent trials. A smaller APS reflects better discrimination (i.e., subject correctly identified frequency sweep direction despite a smaller ms gap between stimuli) and a larger ms value for APS learning reflects more learning, i.e., faster APS with repeated trials. Limits for APS are capped at 0-to-1000 ms; values for APS learning are capped at (-) 1000-to-APS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes \
6 hours of testing in the laboratory. The participant stays at the lab for \
7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week.
Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 19 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes \
6 hours of testing in the laboratory. The participant stays at the lab for \
7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week.
Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 19 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes \
6 hours of testing in the laboratory. The participant stays at the lab for \
7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week.
Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 21 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes \
6 hours of testing in the laboratory. The participant stays at the lab for \
7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week.
Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week.
Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 23 |
| Total | 82 |
Baseline characteristics
| Characteristic | Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39 years | 42 years | 29 years | 30 years | 35 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 6 Participants | 5 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 9 Participants | 13 Participants | 18 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 5 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 3 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 7 Participants | 12 Participants | 31 Participants |
| Region of Enrollment United States | 19 participants | 19 participants | 21 participants | 23 participants | 82 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 29 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 15 Participants | 17 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 38 | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 0 / 38 | 0 / 38 | 0 / 44 | 0 / 44 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 | 0 / 44 | 0 / 44 |
Outcome results
Primary
Prepulse Inhibition (PPI)
PPI was assessed with 42 trials of 6 types: 118 dB 40 ms pulse alone (P) & the same P preceded 10, 20, 30, 60, or 120 ms by a prepulse (pp) 16 dB over background. Startle magnitude (SM), habituation, latency & latency facilitation were measured to interpret changes in PPI. %PPI = 100 x \[(SM on P trials) - (SM on pp+P trials)\] / SM on P trials. Example: SM on P trials = 80 units SM on pp+P trials = 30 units %PPI = 100 x (80-30)/80 = 100 x 50/80 = 62.5% Greater %PPI mean the reflex has been inhibited to a greater extent in the presence of a pp. %PPI can't exceed 100: when SM on pp+P trials = 0, then %PPI = 100 x (SM on P trials - 0)/SM on P trials = 100 x 1 = 100%. However, %PPI can theoretically be infinitely negative since SM on pp+P trials could be infinitely large (prepulse facilitiation (PPF)), i.e. SM is potentiated in the presence of a pp. PPF is normal at very short & very long pp intervals, but not within a species-specific physiological range of intervals.
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Prepulse Inhibition (PPI) | Placebo | 22.629 % inhibition of startle | Standard Deviation 62.657 |
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Prepulse Inhibition (PPI) | Amphetamine | 32.656 % inhibition of startle | Standard Deviation 57.669 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Prepulse Inhibition (PPI) | Amphetamine | 39.545 % inhibition of startle | Standard Deviation 33.429 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Prepulse Inhibition (PPI) | Placebo | 41.162 % inhibition of startle | Standard Deviation 42.103 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Prepulse Inhibition (PPI) | Placebo | 50.626 % inhibition of startle | Standard Deviation 25.85 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Prepulse Inhibition (PPI) | Amphetamine | 45.822 % inhibition of startle | Standard Deviation 31.777 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Prepulse Inhibition (PPI) | Placebo | 50.626 % inhibition of startle | Standard Deviation 29.621 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Prepulse Inhibition (PPI) | Amphetamine | 53.029 % inhibition of startle | Standard Deviation 24.671 |
Secondary
MATRICS Consensus Cognitive Battery Performance (MCCB)
The T-score indicates the performance on a neurocognitive battery of tests. Higher score reflects better performance.
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | MATRICS Consensus Cognitive Battery Performance (MCCB) | amphetamine | 33.842 standardized T-score | Standard Deviation 16.269 |
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | MATRICS Consensus Cognitive Battery Performance (MCCB) | placebo | 31.895 standardized T-score | Standard Deviation 15.937 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | MATRICS Consensus Cognitive Battery Performance (MCCB) | amphetamine | 38.105 standardized T-score | Standard Deviation 12.552 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | MATRICS Consensus Cognitive Battery Performance (MCCB) | placebo | 39.895 standardized T-score | Standard Deviation 11.704 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | MATRICS Consensus Cognitive Battery Performance (MCCB) | placebo | 54.476 standardized T-score | Standard Deviation 11.557 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | MATRICS Consensus Cognitive Battery Performance (MCCB) | amphetamine | 55.476 standardized T-score | Standard Deviation 11.383 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | MATRICS Consensus Cognitive Battery Performance (MCCB) | placebo | 57.870 standardized T-score | Standard Deviation 11.153 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | MATRICS Consensus Cognitive Battery Performance (MCCB) | amphetamine | 56.000 standardized T-score | Standard Deviation 11.286 |
Secondary
Targeted Cognitive Training (TCT): PositScience, Inc.
Auditory discrimination learning: Subjects identify direction (up vs. down) of 2 consecutive sound sweeps. Parameters (e.g. inter-sweep interval, sweep duration) are established for subjects to maintain 80% correct responses. On screen and test days, subjects complete 1h of TCT. Analytic software yields the key measures: auditory processing speed (APS) and APS learning. APS is the shortest inter-stimulus interval at which a subject performs to criteria and APS learning is the difference (ms) between the first APS and the best APS of the subsequent trials. A smaller APS reflects better discrimination (i.e., subject correctly identified frequency sweep direction despite a smaller ms gap between stimuli) and a larger ms value for APS learning reflects more learning, i.e., faster APS with repeated trials. Limits for APS are capped at 0-to-1000 ms; values for APS learning are capped at (-) 1000-to-APS.
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Targeted Cognitive Training (TCT): PositScience, Inc. | placebo | -15.118 msec | Standard Deviation 346.088 |
| Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Targeted Cognitive Training (TCT): PositScience, Inc. | amphetamine | 52.647 msec | Standard Deviation 305.887 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Targeted Cognitive Training (TCT): PositScience, Inc. | amphetamine | 101.000 msec | Standard Deviation 434.379 |
| Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Targeted Cognitive Training (TCT): PositScience, Inc. | placebo | -50.158 msec | Standard Deviation 218.464 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Targeted Cognitive Training (TCT): PositScience, Inc. | placebo | 5.911 msec | Standard Deviation 75.105 |
| Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Targeted Cognitive Training (TCT): PositScience, Inc. | amphetamine | 35.905 msec | Standard Deviation 64.539 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Targeted Cognitive Training (TCT): PositScience, Inc. | placebo | -2.113 msec | Standard Deviation 107.563 |
| Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Targeted Cognitive Training (TCT): PositScience, Inc. | amphetamine | 29.190 msec | Standard Deviation 83.183 |