Intra-cortical Inhibition and Cognitive Deficits in Schizophrenia

NCT05542212 | Unknown

• 1 other identifier: PDJWLL-2021028
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive deficit is a core symptom of schizophrenia (SZ), but its pathological mechanism is poorly understood and the treatment effect is poor. The excitatory-inhibitory microcircuit (E-I) function imbalance formed by inhibitory interneurons and excitatory pyramidal cells in the cerebral cortex is a new mechanism of cognitive deficits in SZ discovered in recent years. Cortical E-I is expected to be a new target for the treatment of cognitive deficits in SZ. Paired transcranial magnetic stimulation (ppTMS)-induced intracortical inhibition (ICI) is dependent on cortical E-I functional integrity. We found that ICI deficiency is stable in SZ and is closely related to cognitive function. Therefore, ICI is likely to be a system-level biomarker for cognitive deficits caused by E-I imbalance. However, no study has yet explored the genetic basis of ICI and its impact on the occurrence, development and treatment response of cognitive deficits in SZ. Based on this, we intend to verify the value of ppTMS-induced ICI as a biomarker of E-I imbalance in SZ patients and normal controls at different stages: 1. To explore the correlation of ICI with multidimensional cognitive deficits and E-I pathway genes; 2. To explore ICI Combining candidate genes and serum inflammatory factors can predict whether TMS can improve the efficacy of cognitive deficits, and can be used for precise treatment of SZ cognitive deficits at the level of pathological mechanisms.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (7)

• Percent Change from Baseline Speed of Information Processing score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by summation of Trail Making Test, BACS Symbol coding and Verbal Fluency scores in MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia)

  Baseline, 2 weeks, 4 weeks

• Percent Change from Attention/Vigilance score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by Continuous Performence Test scores in MATRICS

  Baseline, 2 weeks, 4 weeks

• Percent Change from Working Memory score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by WMS-III SS scores in MATRICS

  Baseline, 2 weeks, 4 weeks

• Percent Change from Verbal Learning score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by HVLT-R scores in MATRICS

  Baseline, 2 weeks, 4 weeks

• Percent Change from Visual Learning score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by BVMT-R scores in MATRICS

  Baseline, 2 weeks, 4 weeks

• Percent Change from Reasoning and Problem Solving score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by NAB Mazes scores in MATRICS

  Baseline, 2 weeks, 4 weeks

• Percent Change from Social Cognition score at 2 weeks and 4 weeks assessed by MATRICS toolkit.

  Measured by MSCEIT Branch 4 scores in MATRICS

  Baseline, 2 weeks, 4 weeks

Secondary Outcomes (1)

• Change from baseline Intracortical inhibition

  Baseline, 2 weeks, 4 weeks

Study Arms (3)

TMS treatment group

EXPERIMENTAL

1. Receive ICI test and MATRICS test. 2. Receive active iTBS treatment on the dlPFC for 4 weeks, 1 treatment a day and 5 days a week.

Device: Transcranial Magenetic Stimulation

TMS Sham Control Group

SHAM COMPARATOR

1. Receive ICI test and MATRICS test. 2. Receive sham TMS treatment on the dlPFC for 4 weeks, 1 treatment a day and 5 days a week.

Device: Sham Transcranial Magenetic Stimulation

Normal Control

NO INTERVENTION

1\. Receive ICI test and MATRICS test.

Interventions

Transcranial Magenetic Stimulation DEVICE

Intermittent Theta Burst Stimulation (iTBS) treatment plan: iTBS treatment for the left dlPFC were used for a total of 20 treatments (one time each Monday to Friday, continuous treatment for 4 weeks).

TMS treatment group

Sham Transcranial Magenetic Stimulation DEVICE

Sham stimulation: The coil angle is set at 90° to the scalp for Sham stimulation of the left dlPFC for a total of 20 treatments (one time each Monday to Friday, continuous treatment for 4 weeks).

TMS Sham Control Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Volunteers or Schizophrenia patients: To be diagnosed as "schizophrenia" by the research doctor using the DSM-IV-TR Axis I Disorder Clinical Examination Guidelines Research Edition (SCID-I/P) ;
• Right-handed;
• Education level of junior high school or above;
• The patient is a permanent resident of Shanghai, and there is no plan to move to another place in the next 3 months, and can cooperate with follow-ups;
• Has signed an informed Consent;
• The patient should meet one of the following two conditions: A. First-time onset of schizophrenia, never taking antipsychotics, and PANSS score ≥ 70 points; B. Schizophrenia with less than 3 episodes Symptomatic patients, whose symptoms were relieved within the past 3 months (PANSS score \<60 points).

You may not qualify if:

• Those who have local or diffuse brain injury or severe brain trauma, and those who have intracranial hypertension;
• Those who have a history of epileptic seizures or a family history of idiopathic epilepsy;
• Those who have paramagnetic or non-paramagnetic metals in the head and neck Implants (such as cochlear implants, titanium clips, etc.);
• Those who have Alcohol dependence and other drug abusers;
• Those who have Severe heart disease, pacemaker or stent implantation;
• Have taken benzodiazepines or received TMS or electroconvulsive therapy within 3 months;
• Patients with moderate or higher depression (HAMD≥17) and anxiety (HAMA≥14) mood;
• Those who are considered unsuitable for enrollment by the researchers.

Sponsors & Collaborators

• Tongji University: lead

Study Sites (1)

Shanghai Pudong New Area Mental Health Center

Shanghai, Shanghai Municipality, 200124, China

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Weiqing Liu, Ph.D

  Shanghai Pudong New Area Mental Health Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weiqing Liu, Ph.D

CONTACT

+8613585699852; lwqkm2012@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 15, 2022
• Study Start: September 28, 2022
• Primary Completion: December 1, 2023
• Study Completion: February 1, 2024
• Last Updated: April 12, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)