Modulation of Repetitive Transcranial Magnetic Stimulation on Hippocampal Neurogenesis and Functional Network in Patients With Schizophrenia

Modulation of rTMS on Hippocampal Neurogenesis and Functional Network in Early Schizophrenia

Based on the hypothesis that high-frequency repetitive transcranial magnetic stimulation(rTMS) on the right dorsolateral prefrontal cortex(DLPFC) and left parietal cortex(LPC) could normalise cognitive abnormalities by promoting hippocampal neurogenesis and cortical-hippocampal function in patients with schizophrenia,this research plan to utilise multimodal functional magnetic imaging method(including structural MRI,resting-state functional magnetic resonance imaging and 1H-MRS) to investigate therapeutic efficacy of intermittent theta burst stimulation (iTBS) on cognitive impairment in SZ patients with memory defects,as well as to elucidate the correlation between treatment effects and hippocampal neuroplasticity.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation(DLPFC); Device: repetitive transcranial magnetic stimulation(LPC)

Detailed Description

This study includes 150 schizophrenia patients and 30 healthy controls.This study will investigate 1).abnormalities of hippocampal neurogenesis in patients with schizophrenia compared to healthy controls by using 1H-MRS technique 2a).potential modulation effects of repetitive transcranial magnetic stimulation(rTMS) on hippocampal neurogenesis and cortical-hippocampal function of patients with schizophrenia 2b).the optimal rTMS therapy pattern on promoting hippocampal neurogenesis and improving cortico-hippocampal function by comparing the outcome of stimulating two regions(right dorsolateral prefrontal cortex or left parietal cortex) respectively 3).the therapeutic efficacy of rTMS on cognitive impairments and other psychotic symptoms of patients with schizophrenia by adopting cognitive function and psychotic symptoms evaluation,as well as to explore the optimal rTMS treatment pattern on cognitive function by comparing the outcome of stimulating two regions(DLPFC or LPC) respectively 4)association between therapeutic efficacy of rTMS on cognitive deficits and rTMS modulation on hippocampal neurogenesis and its network function,in order to elucidate the underlying mechanism of therapeutic effects of rTMS on cognitive dysfunction in schizophrenia.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

• Early schizophrenia group:

Inclusion Criteria:

1. The Structured Interview for Prodromal Symptoms (SIPS) was employed.
2. Meet the diagnostic criteria of Diagnostic and Statistical Manual Diploma in Social Medicine(DSM-V) schizophrenia or schizophreniform psychosis.
3. 18-50years of age,right-handed,normal vision or corrected vision, Han nationality.
4. Disease course less than 5 years.
5. Written informed consent

Observation group: First-episode, In addition to criteria1-3,5,antipsychotics naïve,or antipsychotics withdrawal for more than 3 months.

Intervention group:In addition to criteria 1-6,currently under medication and medically stable for at least 1 month(PANSS score fluctuation<10%);continue the original antipsychotics for at least 1 months after recruitment,with consent of the patients,their psychiatrists and family members.

Exclusion criteria:

Current or past neurological illness,severe physical illness,substance abuse or addiction,alcohol dependence,mental retardation,pregnancy or lactation,extreme agitation, stupor, negative suicide,or those who can not cooperate.A history of MECT within 6 months,or those with contraindications to MRI,rTMS.Medically unstable for at least 1 month (PANSS score fluctuation>10%)

• Healthy controls:

Inclusion Criteria:

1. The Structured Interview for Prodromal Symptoms (SIPS) was employed
2. Matched to the early schizophrenia group in terms of age,sex ratio,handedness,and estimated premorbid IQ
3. normal vision or corrected vision, Han nationality
4. Written informed consent

Exclusion Criteria:

History of psychiatric disease in the subjects themselves or a family history of mental disorder in their first-degree relatives,neurological illness,severe physical illness,substance abuse or alcohol dependence,mental retardation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: rTMS targeting the right DLPFC; 60 patients will be randomly allocated into this group,half of them will receive iTBS on the right DLPFC,while the other half will receive sham stimulation.	Device: repetitive transcranial magnetic stimulation(DLPFC); high frequency(20Hz) repetitive transcranial magnetic stimulation on dorsolateral prefrontal cortex(DLPFC) .Duration:10 days.
SHAM_COMPARATOR: rTMS targeting the left LPC; 60 patients will be randomly allocated into this group,half of them will receive iTBS on left LPC,while the other half will receive sham stimulation.	Device: repetitive transcranial magnetic stimulation(LPC); high frequency(20Hz) repetitive transcranial magnetic stimulation on left parietal cortex(LPC).Duration:10 days
NO_INTERVENTION: Observation group; To investigate the abnormalities of hippocampal neurogenesis in patients with early schizophrenia(n=30) compared to healthy controls(n=30)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in MATRICS Consensus Cognitive Battery	MATRICS Consensus Cognitive Battery	baseline,24 hours after the rTMS treatment,30 days
Change of hippocampal neurogenesis(from baseline)	Quantify neural stem cells in hippocampal by using H1-MRS	baseline,24 hours after the rTMS treatment
Change of cortical-hippocampal functional network(from baseline)	Resting-state fMRI data are acquired	baseline,24 hours after the rTMS treatment
Change from baseline in associative memory	associative memory	baseline,24 hours after the rTMS treatment,30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Positive and Negative Syndrome Scale(PANSS)	Positive and Negative Syndrome Scale(PANSS)	baseline,24 hours after the rTMS treatment,30 days
Change from baseline in the Scale for the Assessment of Negative Symptoms(SANS)	Scale for the Assessment of Negative Symptoms	baseline,24 hours after the rTMS treatment,30 days
Change from baseline in UCSD Performance-based Skills Assessment-Brief(UPSA-B)	UCSD Performance-based Skills Assessment-Brief	baseline,24 hours after the rTMS treatment,30 days

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2019
• Primary Completion (ACTUAL): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: cognitive function; rTMS; MRS; first episode schizophrenia; hippocampal neurogenesis
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: YG2017ZD13

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