Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Dorsal Caudate (DCA) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of the levels of Glx over water in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Medial Prefrontal Cortex (MPFC) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of glx levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.

Memory, attention, reasoning, emotional intelligence, and verbal ability will be assessed using the MCCB before and after 4 weeks of treatment. MATRICS Consensus Cognitive Battery (MCCB) as measure of Neurocognitive/Functional Measures is a standardized battery designed to measure cognitive functioning in people with schizophrenia. The MCCB is represented as a percentile score. This score can go from 0 to 100 where a higher score indicates a better performance. For patients this is a change measure. For control subjects, this is a one time measure.

The WAMI Score at Baseline is a measure of socioeconomic status across countries and culture. The index scale goes from 0 (lower socioeconomic situation) to 1 (highest socioeconomic situation).

Changes in Positive and Negative Symptoms will be assessed across the treatment period using the PANSS.

Participants are rated on a scale of

• (Absent)
• (Minimal)
• (Mild)
• (Moderate)
• (Moderate severe)
• (Severe)
• (Extreme)

to describe Positive, Negative and General symptomatology. Items from each subscale (Positive, Negative, and General) are summed for their respective scales, with lower numbers indicating less severe or absent symptomatology, and higher scores indicating more severe symptoms. A total sum of all subscales is also computed to reflect overall symptom severity.

Positive Subscale: 7 items, minimum score = 7, maximum score = 49 Negative Subscale: 7 items, minimum score = 7, maximum score = 49 General Subscale: '16 items, minimum score = 16, maximum score = 112 Total Score: 30 items, minimum score = 30, maximum score = 210.

For patients this is a change measure. For control subjects, this is a one time measure.

Motor symptomatology associated with tardive dyskinesia (TD) assessed using the AIMS.

The measure consists of 10 items with scale/scores for each item of:

0 None

• Minimal
• Mild
• Moderate
• Severe Higher ratings = higher levels of motor symptoms which is worse. This scale assesses abnormal movements for parts of the body.

The total score is a sum score of items 1-10 and can be 0-40, with 40 being the most symptomatic (i.e., most extrapyramidal side effects, or worse).

Changes in clinical severity over the course of treatment will be monitored using the The Clinical Global Impression Scale (CGI) consists of two items.- Severity scale (CGI-S).

Severity - The first item assesses the patient's current level of mental health symptomatology compared to the clinician's experience with other patients with the same diagnosis. The scale ranges from

• (Normal, not at all ill)
• (Borderline mentally ill)
• (Mildly ill)
• (Moderately ill)
• (Markedly ill)
• (Severely ill)
• (Among the most extremely ill patients)

Improvement - The second item assesses how much the patient's symptomatology has changed since the last clinical visit.

• Very much improved
• Much improved
• Minimally improved
• No change
• Minimally worse
• Much worse
• Very much worse

For patients this is a change measure. For control subjects, this is a one time measure.

The possible score range is 1-7 with 1 being least and 7 being most symptomatic.

Changes in global functioning over the course of treatment will be assessed using the Global Assessment of Functioning (GAF).

Participants are rated 1-100 on their level of functioning, according to clinical observation:

91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 If symptoms are present, they expected reactions to stressors 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Impairment in reality testing or communication or major impairment in several areas 21-30 Behavior influenced by delusions or hallucinations or serious impairment in communication/judgment/inability to function in almost all areas 11-20 Some danger of hurting self or others or occasionally fails to maintain minimal personal hygiene or gross impairment in communication 1-10 Persistent violence risk or lack of self-care 0 No info

For patients this is a change measure. For control subjects, this is a one time measure.

This measure is a self-reported questionnaire which assesses for any use of the following substances within the past month prior to the initial research visit Tobacco (if the respondent indicates that they have used tobacco in the past month, they are additionally asked, "On average, how many cigarettes per day have you smoked in the past 7 days?" Alcohol, Cocaine, Marijuana, Opiates, Amphetamines, phencyclidine (PCP) Other Drugs of Abuse (if the respondent indicates they have used other drugs of abuse within the past month of the initial research visit, they are given the opportunity to "specify" which other drugs of abuse they used

This measure assesses a participant's verbal ability to determine whether they are cognitively able to complete the measures involved in the study. The participant will read from a list of 50 English words and the rater will record whether the pronunciation was correct on a score card for each word spoken. A standard score below the 70th percentile on this measure is indicative of an intellectual disability which would exclude a participant from being clinically and cognitively eligible to complete this study. The potential score range is 0-50. A higher score indicates better cognitive ability. There is only one total score.

This measure assesses a participant's preference regarding which hand they would use to complete a specific task. They have the option to indicate whether they would use they would always or most of the time use their left, right, or both left and right hands to complete each task. This measure assesses handedness based on the amount of responses which indicate the participant is either left handed, right handed, or ambidextrous. Below we specifically report on the number of individuals who were predominantly right handed.