This is a randomized, double-blind, placebo-controlled, multi-centre trial. A total of 300 CHR subjects will be identified in the course of face-to-face interviews using the Structured Interview for Prodromal Syndromes. All participants will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The study duration includes an intervention for 52 consecutive weeks, and additional 1-year follow-up. The primary outcome is 2-year conversion rate of psychosis. Secondary outcomes include 1-year conversion rate of psychosis, the severity and duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and peripheral blood biomarkers of inflammation, oxidative stress and metabolism. Safety monitoring will be performed using scales for side effect, serious adverse events recording, and laboratory tests.

Study design: This study is designed as a randomized, double-blind, placebo-controlled, clinical multi-centre trial. Its main objective is to evaluate the efficacy of SFN vs placebo in decreasing risk and conversion rate of psychosis in CHR population. A total of 300 CHR subjects will be recruited at eight research centres. All participants will be provided withan explanation about the study, and informed consent will be obtained from each participant before participation. The study duration includes an intervention with SFN or placebo for 52 consecutive weeks, and additional 1-year follow-up. The primary outcome is conversion rate of psychosis at the end of follow-up (104 weeks). The secondary outcomes mainly include conversion rate of psychosis at the end of intervention (52 weeks), the severity and the duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and biomarkers of inflammation, oxidative stress and metabolism in peripheral blood. Safety outcomes include side-effects, serious adverse events, laboratory tests, which will be obtained from all participants.

Setting:This study involves eight research centres in China include Shanghai Mental Health Center, Shanghai Xuhui District Mental Health Center, Shanghai Pudong Nanhui Mental Health Center, Suzhou Guangji Hospital, Second Xiangya Hospital of Central South University, Guangzhou Huiai Hospital, Tianjin Anding Hospital, and the First Affiliated Hospital of Zhengzhou University. Shanghai Mental Health Center is the leading centre. Before the trial, standardized training in interview and rating will be provided to all centres equally.

CHR identification: CHR subjects will be identified in the course of face-to-face interviews using the structured interview for prodromal syndromes (SIPS) (Miller et al., 2002; Miller et al., 2003). CHR subjects meet the criteria of prodromal syndromes (COPS) for the attenuated positive symptom syndrome (APSS), brief intermittent psychotic syndrome (BIPS), or genetic risk and deterioration syndrome (GRDS) according to the SIPS. CHR diagnosis will be made by a panel of senior psychiatrists. Severity of CHR subjects' prodromal symptoms will be assessed using the scale of prodromal symptoms (SOPS) (Miller et al., 1999) based on SIPS. In addition, the Positive and Negative Syndrome Scale (PANSS) will be used for rating the severity of psychotic symptoms.

Inclusion criteria:The inclusion criteria of this study are as follows: (a) Subjects meet the criteria of CHR according to SIPS; (b) Subjects will have no history of being medicated with either antipsychotics or mood stabilizers at their first study visit; (c) Age, within the range of 15 to 45 years; (d) Patients and/or their legal guardians for those younger than 18 year old, can understand and sign informed consent, and agree to take the study interventions and complete all visits and examinations.

Exclusion criteria: The exclusion criteria of this study are as follows: (a) A history of schizophrenia or any other psychotic disorders; (b) Severe physical diseases (ie, cardiac and neurologic diseases, brain trauma, liver and kidney diseases, haematopoietic system and immune system dysfunction), or cancer, or other serious complicated diseases; (c) IQ < 70 is assessed by Wechsler Adult Intelligence Scale-Revised in China, or a specific of developmental delay or intellectual disability; (d) Abnormal laboratory test results with clinical significance which will affect the safety of participants as determined by the investigator; (e) A past and/or current abuse of alcohol, amphetamine or any other psychostimulants; (f) Suicidal ideation, plan, or suicidal behaviour in the last 3 months; (g) Clinically significant allergic reaction to broccoli; (h) Pregnancy or preparing for pregnancy, and/or lactation; (i) Participation in another clinical trial within the last 30 days. (j) Other conditions that make the candidate subject unsuitable for this study as determined by the principal investigators (eg, aggressive behaviour, safety concerns, difficulty to complete the follow-up, etc.).

The study will use the following exit/discontinuation criteria: (a) Voluntary discontinuation by the subject who is at any time free to discontinue his or her participation in the study, without prejudice to further assessment and treatment; (b) Severe non-compliance to protocol as judged by the investigator; (c) Subject meets criteria of transition to psychosis; (d) Subject meets exclusion criteria during the intervention (eg, physical diseases, pregnancy, etc.).

Interventions: A total of 300 CHR subjects will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The intervention duration with SFN or placebo is 52 consecutive weeks. SFN will be delivered as its precursor GR along with a conversion enzyme, myrosinase, which converts GR to SFN in the body. The dosage is six active tablets (411 μmol GR) per day. ZHIYINGUOSU, SFN-producing dietary supplement, is provided at no cost by Shenzhen Fushan Biotech Co., Ltd. (China). The placebo group will be given six placebo tablets per day. Active and placebo tablets are manufactured uniformly with same appearance and similar smell and taste by Shenzhen Fushan Biotech Co., Ltd. (China). Patient compliance will be assessed using Brief Adherence Rating Scale (BARS). The BARS is a brief, pencil-paper, clinician-administered adherence assessment instrument. It consists of four items: three questions and an overall visual analogue rating scale to assess the proportion of doses taken by the patient in the past month (Byerly, Nakonezny, & Rush, 2008). Tablets counting will be conducted monthly for the whole intervention period. After intervention, a 1-year follow-up will be conducted. Temporary use of antipsychotics or anti-depressants is allowed in the whole trial based on the recommendation of the treating clinician, and the information of specific drugs, dosage, treatment period and rationale will be recorded.

Safety: To evaluate the tolerability, we conducted a safety test in over 100 subjects, with the daily dosage is six active tablets. Apart from mild gastrointestinal discomfort, no significant safety or side-effect issues were found in this test.We also found that taking the tablets just after meal reduced the risk of gastrointestinal discomfort. Procedures in the proposed study allow the subject to increase the dosage gradually if the subject experiences significant gastrointestinal discomfort. If the subject experiences a serious adverse event his or her participation can be terminated.

Outcomes: Clinical investigators will collect general information such as gender, age, height, weight, body mass index, demographics and medical history. In addition, vital signs and laboratory tests results will be obtained. These will include body temperature, arterial pulse, blood pressure, heart rate, complete blood cell count, blood electrolytes (K, Na, Cl) and liver and kidney function tests.

The primary outcome is the 2-year conversion rate of psychosis at the end of follow-up (104 weeks). Psychosis conversion is operationally defined according to the criteria of POPS (presence of psychotic symptoms in SIPS/SOPS). Two are required: (a) at least one positive symptom is present at a psychotic level of intensity (rated at level '6' using SOPS); (b) any criterion symptom at sufficient frequency and duration or urgency: the symptom has occurred over a period of 1 month for at least 1 hour per day at a minimum average frequency of 4 days per week, or the symptom is seriously disorganizing or dangerous.

The secondary outcomes include: (a) the 1-year conversion rate of psychosis at the end of intervention period (52 weeks); (b) scores of SOPS; (c) scores of PANSS; (d) the duration of psychotic symptoms; (e) Global Assessment of Functioning; (f) individual predictive risk of psychosis calculated by NAPLS-2 psychosis risk calculator (Carrion et al., 2016) and SHARP psychosis risk calculator (Zhang et al., 2019); (g) scores of MATRICS consensus cognitive battery (MCCB) (Kern et al., 2008; Nuechterlein et al., 2008); (h) the number of participants who receive antipsychotic treatment during the trial; (i) levels of peripheral blood biomarkers of inflammation, oxidative stress and metabolism. Others: (a) Serious adverse events; (b) side-effects of SFN and placebo will be assessed by Systematic Assessment For Treatment Emergent Events (SAFTEE) scale (Levine & Schooler, 1986); (c) Compliance to SFN or placebo assessed using BARS; (d) Usage of antidepressants or other medications; (e) plasma and urinary measures of GR metabolites.

Inclusion Criteria:

1. Subjects meet the criteria of CHR according to the Structured Interview for Prodromal Syndromes (SIPS);
2. Subjects will have no history of being medicated with either antipsychotics or mood stabilizers at their first study visit;
3. Age, within the range of 15 to 45 years;
4. Patients and/or their legal guardians for those younger than 18 year old, can understand and sign informed consent, and agree to take the study interventions and complete all visits and examinations.

Exclusion Criteria:

1. A history of schizophrenia or any other psychotic disorders;
2. Severe physical diseases (ie, cardiac and neurologic diseases, brain trauma, liver and kidney diseases, haematopoietic system and immune system dysfunction), or cancer, or other serious complicated diseases;
3. IQ < 70 is assessed by Wechsler Adult Intelligence Scale-Revised in China, or a specific of developmental delay or intellectual disability;
4. Abnormal laboratory test results with clinical significance which will affect the safety of participants as determined by the investigator;
5. A past and/or current abuse of alcohol, amphetamine or any other psychostimulants;
6. Suicidal ideation, plan, or suicidal behaviour in the last 3 months;
7. Clinically significant allergic reaction to broccoli;
8. Pregnancy or preparing for pregnancy, and/or lactation;
9. Participation in another clinical trial within the last 30 days.
10. Other conditions that make the candidate subject unsuitable for this study as determined by the principal investigators (eg, aggressive behaviour, safety concerns, difficulty to complete the follow-up, etc.).