Study on Predictiors and Mechanism of Conversion to Psychosis in Individuals at Ultra-high Risk Group

Considering the complex pathological mechanism and the poor treatment outcomes of schizophrenia, early detection and intervention gradually become the key work for the foundational and clinical research in schizophrenia. Ultra-high risk for psychosis (UHP) is defined as individuals at the prodromal stage of schizophrenia. Early intervention in individual at UHP can effectively delay or even prevent the development of the illness. Long-term longitudinal studies suggested that there are clinical outcomes in people at UHP. Nearly 1/3 of individuals at UHP may be naturally relieved without any intervention, about 1/3 of individuals at UHP will remain at the prodromal stage of schizophrenia, and only 1/3 individuals at UHP will eventually develop schizophrenia. In this regard, it will cause adverse effects on false positive individuals if they accept clinical intervention. Unfortunately, it is difficult to accurately predict which individuals at UHP will make a transition to frank illness. To solve this issue, we explore the association between baseline brain structural and functional networks, methylation modifications, gene expression, neurocognitive function and the clinical outcomes of UHP individuals, and to identify the potential biological and clinical predictors for the long-term outcomes in the individuals at UHP. In addition, we also detect the changes of brain structure and function, methylation status and gene expression in individuals at UHP during follow-up, and further to investigate the etiology and pathogenesis of schizophrenia.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The 2nd Xiangya Hospital of Central South University
      • Contact: Xiaogang Chen, Ph.D; Phone Number: (+86)0731-85531571; Email: Chenxiaogang@csu.edu.cn
      • Contact: Ying He, Ph.D; Phone Number: (+86)0731-85531571; Email: yinghe@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Ultra-high risk for psychosis (UHP) is defined as individuals at the prodromal stage of schizophrenia.

Description

Inclusion Criteria:

• 1. age of 13-30 years;
• 2. meet the diagnostic criteria of COPS prodromal syndrome by SIPS clinical interviews;
• 3. have not received any psychiatric medication;
• 4. be in good health, without major mental illness or physical illness;
• 5. normal intelligence, can be operated on a clinical scale;
• 6. volunteer to participate in the study and sign the written consent form.

Exclusion Criteria:

• 1. exclusion of current or previous psychiatric disorders by SCID interview;
• 2. meet the diagnostic criteria for substance abuse and substance dependence in DSM-IV;
• 3. contraindications for MRI;
• 4. pregnant or lactating women.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Ultra-high risk for psychosis (UHP); Ultra-high risk for psychosis (UHP) is defined as individuals at the prodromal stage of schizophrenia. Inclusion Criteria: age of 13-30 years; meet the diagnostic criteria of COPS prodromal syndrome by SIPS clinical interviews; have not received any psychiatric medication; be in good health, without major mental illness or physical illness; normal intelligence, can be operated on a clinical scale; volunteer to participate in the study and sign the written consent form. Exclusion criteria: exclusion of current or previous psychiatric disorders by SCID interview; meet the diagnostic criteria for substance abuse and substance dependence in DSM-IV; contraindications for MRI; pregnant or lactating women.
Healthy controls; Inclusion Criteria: the gender, age, and education level of the group are matched with the Ultra-high risk group; 13 to 30 years old; right-handed; no history of mental illness; no mental disorder consistent with DSM-IV diagnostic criteria within two or three generations; No contraindications for MRI; volunteer to participate in the study and sign the written consent form. Exclusion criteria: history of disturbance of consciousness over 5 minutes; history of brain organic disease or head injury; history of alcohol and drug dependence; history of coma; history of endocrine disease; abnormity in examination of blood, heart, liver, or renal function; pregnant or lactating women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion to psychosis.	Conversion is operationalized as the criteria of POPS (Presence of Psychotic Symptoms in SIPS/SOPS). Subjects have to demonstrate at least one psychotic level symptom (rated a '6') on at least one of the five P(Positive) symptoms (P1, unusual thought content; P2, suspiciousness; P3, grandiosity; P4, perceptual abnormalities; and P5, disorganized communication), with either sufficient frequency and duration or at a level that is disorganizing or dangerous.	Two years.

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University
• Collaborators: Sun Yat-sen University
• Investigators: Principal Investigator: Xiaogang Chen, Ph.D, Professor

Publications and helpful links

General Publications

• He Y, Kosciolek T, Tang J, Zhou Y, Li Z, Ma X, Zhu Q, Yuan N, Yuan L, Li C, Jin K, Knight R, Tsuang MT, Chen X. Gut microbiome and magnetic resonance spectroscopy study of subjects at ultra-high risk for psychosis may support the membrane hypothesis. Eur Psychiatry. 2018 Sep;53:37-45. doi: 10.1016/j.eurpsy.2018.05.011. Epub 2018 Jun 2.
• He Y, Li Z, Ma X, Yuan L, Ouyang L, Tang J, Tsuang MT, Chen X. Olfactory and cognitive functions in Chinese individuals at clinical high risk for psychosis. Psychiatry Res. 2019 Feb;272:51-53. doi: 10.1016/j.psychres.2018.12.074. Epub 2018 Dec 14.
• He Y, Yuan L, Li Z, Zhou Y, Ma X, Ouyang L, Chen X. Plasma protein levels of brain-derived neurotrophic factor pathways and their association with cognitive performance in patients with clinical high risk for psychosis and first episode psychosis. Schizophr Res. 2019 Apr;206:460-461. doi: 10.1016/j.schres.2018.11.016. Epub 2018 Nov 28. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: May 26, 2019
• First Submitted That Met QC Criteria: May 26, 2019
• First Posted (ACTUAL): May 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 29, 2019
• Last Update Submitted That Met QC Criteria: May 26, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; Ultra-high risk for psychosis; Predictors; Pathogenesis
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: 81871056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No