Psychotic Disorder NOS, Schizoaffective Disorder, Schizophrenia, Schizophreniform
Conditions
Brief summary
The primary objective of this study is to determine if NAC, added to existing antipsychotic treatment, is superior to placebo for cortical erosion in patients with early stage psychosis. The primary hypothesis is that there will be significantly less cortical erosion as measured by cortical thickness, cortical volume and cortical white matter density (assessed by DTI) in patients treated for 12 months with NAC as compared to those treated with placebo. The secondary objectives of this study are to determine if 12 months of NAC add-on treatment is superior to placebo for fMRI determined working memory and semantic memory tasks, cortical MR spectroscopy measures (glutathione, N-acetylaspartate, and glutamine/glutamate levels), electrophysiologically determined attention measures (e.g., mismatch negativity, P300), symptoms, functional measures and cognitive functioning.
Detailed description
Schizophrenia is a severe, debilitating illness that typically begins during the teen-age years and early twenties, and worsens over time as it evolves into a chronic, life-long disorder. Existing treatments suppress psychotic symptoms but do not prevent the evolution of underlying disease processes that results in poor, long term outcomes. Recent studies have shown that progressive erosion of cortical mass occurs during the early stages of schizophrenia (1-3). The investigators hypothesize that arresting cortical erosion during the early phases of schizophrenia will prevent subsequent clinical deterioration and the descending course of illness associated with this disorder. The investigators propose to establish a research program that will assess the ability of agents with neuroprotective properties to halt cortical loss and thereby prevent subsequent clinical deterioration. N-acetyl cysteine (NAC) is an attractive molecule for the proposed study because of two of its mechanistic properties. First, it is an established neuroprotective agent. NAC is a precursor to glutathione which is a primary detoxifier of reactive oxygen and other radical molecules which damage neuronal tissue (4-6). Glutathione deficiencies have been well documented in schizophrenia (7, 8). Second, NAC modulates glutamate release. NMDA hypofunction and altered glutamate release have been hypothesized to contribute to the cortical atrophy observed in early stage schizophrenia (9, 10). NAC has been shown to antagonize both the phencyclidine (PCP) effects of increased frontal glutamate levels and induction of social isolation in rodents (11). PCP is a pharmacological model of schizophrenia. In a controlled clinical trial of patients with chronic schizophrenia, NAC improved mismatch negativity, a pre-attentive measure of cortical information processing that has been consistently implicated in the pathophysiology of schizophrenia and has been shown to correlate with cortical erosion in early stage patients (12, 13). In a double-blind, placebo controlled clinical trial of chronic schizophrenic patients, NAC significantly improved general psychopathology scores, negative symptoms and extrapyramidal symptoms (14). NAC was well tolerated with no significant effects on any safety parameter or adverse events. The favorable tolerability of NAC has been further demonstrated in a recent study conducted at IUSM Riley Hospital in children (ages 4 to 12 years) with autism at relatively high doses (dose range of 900 to 4200 mg/day) in which there were no serious adverse events reported and NAC was well tolerated (15). The investigators propose to determine if NAC has disease modifying potential in early stage schizophrenia. The investigators hypothesize that NAC will improve measures of cortical integrity in early stage schizophrenia and these brain effects will be related to improvements in negative symptoms and cognitive functioning. Primary outcome measures in the trials will be serial assessments of cortical integrity using magnetic resonance structural (cortical thickness, cortical volume, diffuses tensor imaging, DTI). In addition the investigators will assess the possible effects of NAC treatment on other parameters linked to cortical erosion including fMRI coupled with working memory and semantic memory tasks, MR spectroscopy (cortical glutathione, N-acetylaspartate, and glutamine/glutamate levels) and electrophysiological measures (e.g., mismatch negativity, P300). The investigators will also determine the relationship between effects of NAC on negative symptoms, positive symptoms, functional status, cognition (BACS), and safety parameters; and brain indices.
Interventions
DRUGN-Acetyl Cysteine
NAC and matched placebo will be supplied in unmarked capsules. Each NAC capsule will contain 480 mg of NAC. Dosing will begin at 480 mg/d and titrated up by 480 mg/d each week until a maximum dose of 2880 mg/d (BID) is reached. This approximate dose was effective and well tolerated in a recent study of treatment refractory obsessive-compulsive disorder by Krystal and colleagues at Yale (16). In addition, a double-blind placebo controlled trial recently completed at IUSM Riley Hospital in children (age 4 to 12 years) with autism spectrum disorders used doses ranging from 900 mg/day to 4200 mg/day and reported no serious adverse events and found the agent well tolerated (15). Dose adjustments downward to 1920 mg/d will be permitted if tolerability issues are encountered at the maximum dose
OTHERsugar pill
matched placebo will be supplied in unmarked capsules. Dosing regimen will be the same as in the N-Acetyl Cysteine arm.
Sponsors
Stanley Medical Research Institute
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
16 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
SUBJECTS DIAGNOSED WITH A PSYCHOTIC DISORDER Inclusion Criteria: * Patients with a DSM-IV diagnosis of schizophrenia, schizophreniform, schizoaffective, psychosis disorder NOS * Age range 16-35 years * Male or female * Within 2 years of the first onset of psychotic symptoms that resulted in work/school/social dysfunction and/or treatment (PI will review potential subjects who have been experiencing symptoms \>2 years but \<5 years and will allow to enter the trial on a case-by-case basis) * Ability to provide informed consent and/or assent (all subjects) * For subjects 16 and 17 years of age, parental/guardian consent
Exclusion criteria
* Unstable medical conditions * Active seizure disorder * Pregnant or lactating women * Females unwilling to utilize birth control * Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculoperitoneal shunt (because of MR studies). * Known IQ less than 70 * DSM-IV-TR diagnosis of substance dependence (with the exception of nicotine or caffeine dependence) * Psychotic symptoms secondary to substance use * Considered a high risk for suicidal acts - active suicidal ideation with intent to act as determined by clinical interview HEALTHY CONTROL SUBJECTS The comparison subjects will consist of 40 healthy normal volunteers recruited from the community who will be age and gender matched to subjects diagnosed with a psychotic disorder entering the NAC treatment study Inclusion Criteria: 1. Age range of 18-30 (inclusive) and able to give voluntary informed consent (Note: Subjects diagnosed with a psychotic disorder under the age of 18 will be age matched to control subjects aged 18). 2. Male or Female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortical Thickness | 12 months | We anticipate that 12 months treatment with NAC as an add-on treatment will show significantly less cortical erosion as measured by cortical thickness than treatment with placebo |
| Cortical Volume | 12 months | We anticipate that 12 months treatment with NAC as an add-on treatment will show a difference in cortical volume than treatment with placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attention Measures | 12 months | determine if 12 months of NAC add-on treatment is superior to placebo for attention measures (e.g., mismatch negativity, P300) as measured by electrophysiology methods. Electrophysiology measures will be recorded from a 64 channel, silver/silver-chloride scalp electrode montage. |
| Symptoms of a Psychotic Disorder | 12 months | Determine if 12 months of NAC add-on treatment is superior to placebo for symptom management of a psychotic disorder as assessed by the Positive and Negative Syndrome Scale (PANSS). The PANSS is a semi-structured interview, containing 30 items that assess positive, negative, and general psychopathology symptoms. Positive symptoms=7 items, negative symptoms=7 items, and general psych.=16 items. Scores for each item range from 1-absent to 7-extreme. To calculate total score, all items on the scale are summed to yield a score from 30-210,a lower score reflecting fewer symptoms. To calculate factor scores various items from positive, negative, and general psych. are summed together to yield Cognitive/Disorganized, Negative, and Positive factor scores. Cog/Disorg factor scores sum 7 items, ranging from 7-49. Neg factor scores sum 7 items, ranging from 7-49. Pos factor scores sum 8 items, ranging from 8-56. For all factor scores a lower score reflects less symptom severity. |
| Working Memory | Baseline and 12 months | determine if 12 months of NAC add-on treatment is superior to placebo as determined by brain activity during n-back working memory task during fMRI. |
| Functional Status | Baseline and 12 months | determine if 12 months of NAC add-on treatment is superior to placebo for functional measures as measured by the Personal and Social Performance Scale (PSP). The PSP scale is a 100-point, single item, clinician rated scale to assess 4 domains of functioning, including personal and social relationships, socially useful activities, self care and disturbing and aggressive behaviors. A score from 0-100 is generated, with a higher score representing better performance. |
| Mismatch Negativity Voltage Differences | 12 months | Determine if 12 months of NAC add-on treatment is superior to placebo for attention measures as measured by the voltage of the Mismatch Negativity (MMN) of the event-related potential. The voltage of the peak MMN response was measured at the Fz electrode site. |
| Cognitive Functioning | Baseline and 12 months | determine if 12 months of NAC add-on treatment is superior to placebo for cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS is a battery specifically designed to measure treatment-related changes in cognition by utilizing 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. |
| Number of Participants With Glutamine/Glutamate Level Changes | 12 months | Identify number of participants with 12 months of NAC treatment who had glutamine/glutamate level changes as measured by cortical magnetic resonance spectroscopy measures. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-Acetyl Cysteine NAC and matched placebo will be supplied in unmarked capsules. Each NAC capsule will contain 600 mg of NAC. Dosing will begin at 600 mg/d and titrated up over 5 weeks until a maximum dose of 3600 mg/d is reached. Dose adjustments downward to 1920 mg/d will be permitted if tolerability issues are encountered at the maximum dose. | 30 |
| Sugar Pill matched placebo
sugar pill: matched placebo will be supplied in unmarked capsules. Dosing regimen will be the same as in the N-Acetyl Cysteine arm. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Sugar Pill | N-Acetyl Cysteine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 28 Participants | 57 Participants |
| Age, Continuous | 25.0 years STANDARD_DEVIATION 5.2 | 22.2 years STANDARD_DEVIATION 4.2 | 23.1 years STANDARD_DEVIATION 4.8 |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 24 Participants | 23 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 30 | 27 / 30 |
| serious Total, serious adverse events | 3 / 30 | 2 / 30 |
Outcome results
Primary
Cortical Thickness
We anticipate that 12 months treatment with NAC as an add-on treatment will show significantly less cortical erosion as measured by cortical thickness than treatment with placebo
Time frame: 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Cortical Thickness | Left Total Cortical Thickness at 52 Weeks | 2.53 mm | Standard Error 0.03 |
| N-Acetyl Cysteine | Cortical Thickness | Right Total Cortical Thickness at 52 weeks | 2.51 mm | Standard Error 0.03 |
| N-Acetyl Cysteine | Cortical Thickness | Left Caudal Middle Frontal Thickness at 52 Weeks | 2.59 mm | Standard Error 0.04 |
| N-Acetyl Cysteine | Cortical Thickness | Right Caudal Middle Frontal Thickness at 52 Weeks | 2.49 mm | Standard Error 0.04 |
| N-Acetyl Cysteine | Cortical Thickness | Left Middle Temporal Thickness at 52 Weeks | 2.84 mm | Standard Error 0.04 |
| N-Acetyl Cysteine | Cortical Thickness | Right Middle Temporal Thickness at 52 Weeks | 2.91 mm | Standard Error 0.04 |
| N-Acetyl Cysteine | Cortical Thickness | Left Superior Parietal Thickness at 52 Weeks | 2.16 mm | Standard Error 0.03 |
| N-Acetyl Cysteine | Cortical Thickness | Right Superior Parietal Thickness at 52 Weeks | 2.17 mm | Standard Error 0.03 |
| Sugar Pill | Cortical Thickness | Right Superior Parietal Thickness at 52 Weeks | 2.18 mm | Standard Error 0.04 |
| Sugar Pill | Cortical Thickness | Left Total Cortical Thickness at 52 Weeks | 2.54 mm | Standard Error 0.03 |
| Sugar Pill | Cortical Thickness | Left Middle Temporal Thickness at 52 Weeks | 2.87 mm | Standard Error 0.05 |
| Sugar Pill | Cortical Thickness | Right Total Cortical Thickness at 52 weeks | 2.52 mm | Standard Error 0.03 |
| Sugar Pill | Cortical Thickness | Left Superior Parietal Thickness at 52 Weeks | 2.21 mm | Standard Error 0.04 |
| Sugar Pill | Cortical Thickness | Left Caudal Middle Frontal Thickness at 52 Weeks | 2.57 mm | Standard Error 0.04 |
| Sugar Pill | Cortical Thickness | Right Middle Temporal Thickness at 52 Weeks | 2.95 mm | Standard Error 0.05 |
| Sugar Pill | Cortical Thickness | Right Caudal Middle Frontal Thickness at 52 Weeks | 2.49 mm | Standard Error 0.05 |
Primary
Cortical Volume
We anticipate that 12 months treatment with NAC as an add-on treatment will show a difference in cortical volume than treatment with placebo
Time frame: 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Cortical Volume | Total Cortical Gray Matter Volume at 52 Weeks | 233.0 mm^3 | Standard Error 5.2 |
| N-Acetyl Cysteine | Cortical Volume | Total Cortical White Matter Volume at 52 Weeks | 423.8 mm^3 | Standard Error 11.5 |
| Sugar Pill | Cortical Volume | Total Cortical Gray Matter Volume at 52 Weeks | 235.8 mm^3 | Standard Error 6 |
| Sugar Pill | Cortical Volume | Total Cortical White Matter Volume at 52 Weeks | 418.5 mm^3 | Standard Error 13.1 |
Secondary
Attention Measures
determine if 12 months of NAC add-on treatment is superior to placebo for attention measures (e.g., mismatch negativity, P300) as measured by electrophysiology methods. Electrophysiology measures will be recorded from a 64 channel, silver/silver-chloride scalp electrode montage.
Time frame: 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Attention Measures | EEG Alpha power | 3.81 Hz | Standard Error 0.4 |
| N-Acetyl Cysteine | Attention Measures | Auditory Steady State Response 40 Hz | 0.05 Hz | Standard Error 0.01 |
| N-Acetyl Cysteine | Attention Measures | EEG Delta power | 2.96 Hz | Standard Error 0.25 |
| N-Acetyl Cysteine | Attention Measures | EEG Gamma power | 0.37 Hz | Standard Error 0.03 |
| N-Acetyl Cysteine | Attention Measures | EEG Theta power | 1.33 Hz | Standard Error 0.3 |
| Sugar Pill | Attention Measures | EEG Theta power | 1.33 Hz | Standard Error 0.35 |
| Sugar Pill | Attention Measures | EEG Gamma power | 0.47 Hz | Standard Error 0.05 |
| Sugar Pill | Attention Measures | EEG Alpha power | 4.18 Hz | Standard Error 0.73 |
| Sugar Pill | Attention Measures | Auditory Steady State Response 40 Hz | 0.06 Hz | Standard Error 0.01 |
| Sugar Pill | Attention Measures | EEG Delta power | 3.46 Hz | Standard Error 0.35 |
Secondary
Cognitive Functioning
determine if 12 months of NAC add-on treatment is superior to placebo for cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS is a battery specifically designed to measure treatment-related changes in cognition by utilizing 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Cognitive Functioning | BACS Composite Score Baseline | 26.91 scores on a scale | Standard Error 3.22 |
| N-Acetyl Cysteine | Cognitive Functioning | BACS Composite Score at 52 Weeks | 30.03 scores on a scale | Standard Error 3.22 |
| Sugar Pill | Cognitive Functioning | BACS Composite Score Baseline | 27.70 scores on a scale | Standard Error 3.35 |
| Sugar Pill | Cognitive Functioning | BACS Composite Score at 52 Weeks | 29.37 scores on a scale | Standard Error 3.36 |
Secondary
Functional Status
determine if 12 months of NAC add-on treatment is superior to placebo for functional measures as measured by the Personal and Social Performance Scale (PSP). The PSP scale is a 100-point, single item, clinician rated scale to assess 4 domains of functioning, including personal and social relationships, socially useful activities, self care and disturbing and aggressive behaviors. A score from 0-100 is generated, with a higher score representing better performance.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Functional Status | PSP Adjusted Score at Baseline | 62.51 scores on a scale | Standard Error 2.26 |
| N-Acetyl Cysteine | Functional Status | PSP Adjusted Score at 52 Weeks | 64.51 scores on a scale | Standard Error 2.33 |
| Sugar Pill | Functional Status | PSP Adjusted Score at Baseline | 64.46 scores on a scale | Standard Error 2.35 |
| Sugar Pill | Functional Status | PSP Adjusted Score at 52 Weeks | 65.44 scores on a scale | Standard Error 2.42 |
Secondary
Mismatch Negativity Voltage Differences
Determine if 12 months of NAC add-on treatment is superior to placebo for attention measures as measured by the voltage of the Mismatch Negativity (MMN) of the event-related potential. The voltage of the peak MMN response was measured at the Fz electrode site.
Time frame: 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| N-Acetyl Cysteine | Mismatch Negativity Voltage Differences | -2.51 microvolts | Standard Error 0.28 |
| Sugar Pill | Mismatch Negativity Voltage Differences | -3.44 microvolts | Standard Error 0.38 |
Secondary
Number of Participants With Glutamine/Glutamate Level Changes
Identify number of participants with 12 months of NAC treatment who had glutamine/glutamate level changes as measured by cortical magnetic resonance spectroscopy measures.
Time frame: 12 months
Population: Several subjects were excluded from the MR spectroscopy measures due to visible motion between image acquisitions. Data were not collected for the Placebo group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N-Acetyl Cysteine | Number of Participants With Glutamine/Glutamate Level Changes | 18 Participants |
| Sugar Pill | Number of Participants With Glutamine/Glutamate Level Changes | 0 Participants |
p-value: 0.32ANOVA
Secondary
Symptoms of a Psychotic Disorder
Determine if 12 months of NAC add-on treatment is superior to placebo for symptom management of a psychotic disorder as assessed by the Positive and Negative Syndrome Scale (PANSS). The PANSS is a semi-structured interview, containing 30 items that assess positive, negative, and general psychopathology symptoms. Positive symptoms=7 items, negative symptoms=7 items, and general psych.=16 items. Scores for each item range from 1-absent to 7-extreme. To calculate total score, all items on the scale are summed to yield a score from 30-210,a lower score reflecting fewer symptoms. To calculate factor scores various items from positive, negative, and general psych. are summed together to yield Cognitive/Disorganized, Negative, and Positive factor scores. Cog/Disorg factor scores sum 7 items, ranging from 7-49. Neg factor scores sum 7 items, ranging from 7-49. Pos factor scores sum 8 items, ranging from 8-56. For all factor scores a lower score reflects less symptom severity.
Time frame: 12 months
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Symptoms of a Psychotic Disorder | PANSS Total Score at 52 Weeks | 46.79 scores on a scale | Standard Error 2.24 |
| N-Acetyl Cysteine | Symptoms of a Psychotic Disorder | PANSS Cognitive/Disorganized Factor at 52 Weeks | 11.09 scores on a scale | Standard Error 0.68 |
| N-Acetyl Cysteine | Symptoms of a Psychotic Disorder | PANSS Negative Symptom Factor at 52 Weeks | 10.35 scores on a scale | Standard Error 1.02 |
| N-Acetyl Cysteine | Symptoms of a Psychotic Disorder | PANSS Positive Symptom Factor at 52 Weeks | 14.77 scores on a scale | Standard Error 1.05 |
| Sugar Pill | Symptoms of a Psychotic Disorder | PANSS Positive Symptom Factor at 52 Weeks | 16.38 scores on a scale | Standard Error 1.09 |
| Sugar Pill | Symptoms of a Psychotic Disorder | PANSS Total Score at 52 Weeks | 56.44 scores on a scale | Standard Error 2.32 |
| Sugar Pill | Symptoms of a Psychotic Disorder | PANSS Negative Symptom Factor at 52 Weeks | 13.22 scores on a scale | Standard Error 1.06 |
| Sugar Pill | Symptoms of a Psychotic Disorder | PANSS Cognitive/Disorganized Factor at 52 Weeks | 13.68 scores on a scale | Standard Error 0.7 |
Secondary
Symptoms of a Psychotic Disorder
determine if 12 months of NAC add-on treatment is superior to placebo for symptom management of a psychotic disorder as assessed by the Clinical Global Impressions Severity Scale (CGI-S). The CGI-S is used for repeated evaluations of global psychopathology and is a 7 point Likert scale rating severity on a scale of 1 (normal, not ill) to 7 (very severely ill).
Time frame: 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| N-Acetyl Cysteine | Symptoms of a Psychotic Disorder | 2.78 scores on a scale | Standard Error 0.18 |
| Sugar Pill | Symptoms of a Psychotic Disorder | 3.00 scores on a scale | Standard Error 0.19 |
Secondary
Working Memory
determine if 12 months of NAC add-on treatment is superior to placebo as determined by brain activity during n-back working memory task during fMRI.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-Acetyl Cysteine | Working Memory | Baseline pre exposure to NAC | 0.299 Bold signal change | Standard Deviation 0.2 |
| N-Acetyl Cysteine | Working Memory | 6 months exposure to NAC | 0.351 Bold signal change | Standard Deviation 0.24 |
| N-Acetyl Cysteine | Working Memory | 12 months exposure to NAC | 0.315 Bold signal change | Standard Deviation 0.185 |
| Sugar Pill | Working Memory | Baseline pre exposure to NAC | 0.356 Bold signal change | Standard Deviation 0.24 |
| Sugar Pill | Working Memory | 6 months exposure to NAC | 0.398 Bold signal change | Standard Deviation 0.28 |
| Sugar Pill | Working Memory | 12 months exposure to NAC | 0.406 Bold signal change | Standard Deviation 0.23 |