N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis

Positive and Negative Symptom Scale was used to assess psychopathology. The sum of items N1 - N7 including N1) blunted affect, N2) emotional withdrawal, N3) poor rapport, N4) passive apathetic social withdrawal, N5) difficulty in abstract thinking, N6) lack of spontaneity and flow of conversation, and N7) sterotyped thinking were used to analyze negative symptoms of schizophrenia and were assessed for the previous week: RATING SCALE 1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

Time frame: at 6 months

Population: Analysis was done with those who completed the 6 month treatment protocol.

Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.

Time frame: at 6 months

Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. The level of glutathione is measured in blood cells.

Time frame: at 6 months

The MATRICS is neurocognitive battery designed to assess cognition. Sustained attention and Vigilance is a composite score based on the Continuous Performance Test -Identical Pairs. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

The MATRICS is neurocognitive battery designed to assess cognition. Problem Solving is a composite score based on the NAB Mazes. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

The MATRICS is neurocognitive battery designed to assess cognition. Processing speed is a composite score including the following tests: Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

The MATRICS is neurocognitive battery designed to assess cognition. Verbal Learning is a composite score based on the Hopkins Verbal Learning Test-Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

The MATRICS is neurocognitive battery designed to assess cognition. Visual Learning is a composite score based on the Brief Visuospatial Memory test - Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

The MATRICS is neurocognitive battery designed to assess cognition. Working Memory score is a composite score based on the following sub-test WMS-III Spatial Span and Letter-Number Span. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.

Time frame: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

Positive and Negative Symptom Scale was used to assess psychopathology. The Positive symptom subscale of schizophrenia includes the sum of items P1 -P7 including P1) Delusions, P2) conceptual Disorganization, P3) Hallunicatory Behavior, P4) Excitement, P5) Grandiosity, P6) Suspiciousness and Persecution, and P7) Hostility and were assessed for the previous week: RATING SCALE 1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

Time frame: at 6 months

Population: Analysis was done with participants who completed the 6 month treatment phase

Measure Description: Clinical Measure of Global level of Symptoms (Sx) and Functioning from 1 (Worst) to 100 (Best) in groups of 10: 100 - 91: Superior functioning 90 - 81: Absent or minimal Sx 80 - 71: If symptoms are present and expected 70 - 61:Some mild Sx 60 - 51: Moderate Sx 50 - 41: Serious Sx 40 - 31: Some impairment in reality testing or communication 30 - 21: Behavior is considerably influenced by delusions or hallucinations 20 - 11: Some danger of hurting self or others 10 - 1: Persistent danger of severely hurting self or others

Time frame: at 6 months

Brain marker, glutamate, was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutamate is an excitatory neurotransmitter in the brain.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

GPxBC is a measurement of glutathiione peroxidase enzymatic activity in glutathione synthesis and the redox system in blood cells. Measured as umol/min/gHb from blood cells.

Time frame: at 6 months

Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Time frame: at 6 months

Population: The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.

Measure of social and occupational functioning using the Social and Occupational Functioning Assessment Scale Measure Description: Rating of Overall Social and Occupational Functioning on a scale of 1 (worst) to 100 (best) in groups of 10: 100-91: Superior functioning 90-81: Good functioning 80-71: Slight impairment 70-61: Some difficulty 60-51: Moderate difficulty 50-41: Serious impairment 40-31: Major impairment 30-21: Inability to function in almost all areas 20-11: Unable to function independently 10-1: Unable to function without harming self or others

Time frame: at 6 months