The Difference of Grey Matter Volume Among the Patients of Schizophrenia

Schizophrenia is a heritable complex phenotype whose symptoms can be clustered into three domains: positive symptoms, negative symptoms and cognitive impairments. Constellations of negative symptoms in SCZ are composed of diminished motivation and pleasure, such as asociality, anhedonia, and avolition, or diminished expressivity such as blunted affect and alogia. Negative symptoms are associated with decreased quality of life and poor functional outcomes. Although antipsychotics are generally effective on positive symptoms, they are poorly effective on negative symptoms Currently, there are no licensed targeted medications for negative symptoms. In view of these problems, considerable interest in identifying new treatment targets for negative symptoms has grown over the past decade. Despite intense efforts in brain imaging that have opened new opportunities for addressing these issues, the neurobiological mechanism of negative symptoms remains unclear.

Structural brain measures from magnetic resonance imaging (MRI) are highly heritable and representatively have high reproducibility and low measurement error. Prior neuroimaging researches have consistently shown neuroanatomical abnormalities in the brains of individuals with SCZ, with the most robust and consistent group-level structural differences in widespread reduced volumes of hippocampal thalamus, amygdala and nucleus accumbens. SCZ have been associated with widespread structural brain abnormalities, but results from neuroimaging studies have been inconsistent.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Cognitive Dysfunction; Neuroimaging
• Intervention / Treatment: Other: This is not an intervention study

Detailed Description

Schizophrenia (SCZ) is a heritable complex phenotype whose symptoms can be clustered into three domains: positive symptoms, negative symptoms and cognitive impairments. Constellations of negative symptoms in SCZ are composed of diminished motivation and pleasure, such as asociality, anhedonia, and avolition, or diminished expressivity such as blunted affect and alogia. Negative symptoms are associated with decreased quality of life and poor functional outcomes. Although antipsychotics are generally effective on positive symptoms, they are poorly effective on negative symptoms Currently, there are no licensed targeted medications for negative symptoms. In view of these problems, considerable interest in identifying new treatment targets for negative symptoms has grown over the past decade. Despite intense efforts in brain imaging that have opened new opportunities for addressing these issues, the neurobiological mechanism of negative symptoms remains unclear.

Structural brain measures from magnetic resonance imaging (MRI) are highly heritable and representatively have high reproducibility and low measurement error. Prior neuroimaging researches have consistently shown neuroanatomical abnormalities in the brains of individuals with SCZ, with the most robust and consistent group-level structural differences in widespread reduced volumes of hippocampal thalamus, amygdala and nucleus accumbens. SCZ have been associated with widespread structural brain abnormalities, but results from neuroimaging studies have been inconsistent.

• Study Type: Observational
• Enrollment (Actual): 253

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population will include individuals with psychotic disorders (schizophrenia or schizophreniform disorder) and healthy comparison participants(without personal or family history of psychotic disorders). Participants will be women and men, all races and ethnicities. Participants with schizophrenia/schizophreniform disorder will be aged 18-60 years.

Description

Inclusion Criteria:

• All the patients satisfied the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) diagnostic criteria for schizophrenia or schizophreniform disorder.
• Women and men
• 18 to 60 years of age
• Able and willing to provide written informed consent; and willing to commit to the study protocol
• Able to read, speak, and understand Chinese

Exclusion Criteria:

• (i) were <18 years or >60 years
• (ii) psychotic patients in unstable clinical condition (e.g., being aggressive and uncooperative)
• (iii) had major neurological or other psychiatric disorders, or significant medical condition including neurological disease, severe cardiovascular, hepatic, renal diseases
• (iv)had MRI abnormalities, or had MRI contraindications.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PNS group; The patients with prominently negative symptoms (PNS) had a greater score on the negative than on the positive subscale of the PANSS, a negative symptoms score > 20, and at least one of items from PANSS negative symptoms scale ≥ 4 points	Other: This is not an intervention study
PPS group; The patients with predominantly positive symptoms (PPS) had a greater score on the positive than on the negative subscale of the PANSS	Other: This is not an intervention study
Control; Healthy control	Other: This is not an intervention study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMV difference among PNS, PPS and HC groups.	PNS、PPS and HC will undergo Magnetic Resonance Imaging (MRI) at baseline. And the GMV of the three group was collected and analysed.1)The PNS patients showed longer duration, less positive symptoms, more severe PANSS-total symptoms and negative symptoms (all p values ≤ 0.001) than PPS. 2)compared with HC group, PPS group showed reduced GMV in the right orbital gyrus.	baseline
Identifying genes associated with GMV alterations in PNS.	1)PLS1 weighted gene expression profile was positively correlated with PNS vs. HC GMV difference.2)The 2 overlapping genes (GRM7, RASSF7) exhibited significant negative correlations with regional GMV alterations in schizophrenia patients with predominantly negative symptoms.	baseline
PPI network construction and hub gene identification.	1)PPI analysis of hub genes revealed a network consisting of 10 connected proteins and 33 edges, which is remarkably significantly higher than the expected 2 edges.2)PPI analysis revealed a network consisting of 461 connected proteins and 706 edges, which is remarkably significantly higher than the expected 621 edges	baseline

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: GMV-2013

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