Intra-cortical Inhibition and Cognitive Deficits in Schizophrenia

Last updated: April 10, 2023
Sponsor: Tongji University
Overall Status: Active - Recruiting

Phase

N/A

Condition

Tourette's Syndrome

Memory Loss

Dementia

Treatment

N/A

Clinical Study ID

NCT05542212
PDJWLL-2021028
  • Ages 18-60
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Healthy Volunteers or Schizophrenia patients: To be diagnosed as "schizophrenia" bythe research doctor using the DSM-IV-TR Axis I Disorder Clinical ExaminationGuidelines 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 toanother 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 ofschizophrenia, never taking antipsychotics, and PANSS score ≥ 70 points; B.Schizophrenia with less than 3 episodes Symptomatic patients, whose symptoms wererelieved within the past 3 months (PANSS score <60 points).

Exclusion

Exclusion Criteria:

  • Those who have local or diffuse brain injury or severe brain trauma, and those whohave intracranial hypertension;
  • Those who have a history of epileptic seizures or a family history of idiopathicepilepsy;
  • 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 3months;
  • Patients with moderate or higher depression (HAMD≥17) and anxiety (HAMA≥14) mood;
  • Those who are considered unsuitable for enrollment by the researchers.

Study Design

Total Participants: 200
Study Start date:
September 28, 2022
Estimated Completion Date:
February 29, 2024

Study Description

Study 1. In schizophrenia patients at different stages and normal controls, ppTMS-induced M1 intracortical inhibition was used as a candidate biomarker to comprehensively analyze its correlation with cognitive deficits in the seven dimensions of schizophrenia;

  1. To compare the differences in ppTMS-induced intracortical inhibition (SICI and LICI) in the M1 area between schizophrenic patients in the first drug-free period and remission period, and between patients and normal controls;

  2. To compare the differences in the 7 cognitive function dimensions of the MCCB between schizophrenic patients in the first episode of drug-free period and remission period, and between patients and normal controls;

  3. Analyze the correlation between intracortical inhibition (SICI and LICI) and seven cognitive function dimensions in first-episode drug-free schizophrenia, remission schizophrenia, and normal controls.

Study 2. In patients with schizophrenia and normal controls, to investigate whether there is a correlation between ppTMS-induced intracortical suppression in the M1 area and susceptibility genes that can regulate the function of the E-I microcircuit;

  1. Compare the 12 susceptibility genes related to the functional regulation of the E-I microcircuit between patients with schizophrenia and normal controls (including: GABA receptor encoding genes of different subtypes, NMDA receptor encoding genes and others that may affect E-I The distribution difference of 23 single nucleotide polymorphism sites (SNP) in the candidate genes of microcirculation and cognitive function) between the two groups;

  2. Compare the effects of the genotypes of each SNP site and the haplotypes of each SNP on the intracortical inhibitory indicators (SICI and LICI) of schizophrenia in the above samples;

  3. Further analyze whether the SNP sites found in the previous part that have a significant impact on SICI and LICI also affect cognitive functions in certain dimensions in the above samples. And analyze the potential causal relationship between susceptibility genes and intracortical inhibitory indicators and cognitive deficits;

Study 3. Intermittent theta-burst transcranial magnetic stimulation (iTBS) or sham stimulation intervention on the left dlPFC in patients with schizophrenia, analysis of the efficacy of iTBS in improving cognition and intracortical inhibition indicators at baseline and during the treatment interval and treatment The relationship between post-variation and E-I microcircuit function-related susceptibility genes and intracortical inhibition to predict the cognitive efficacy of iTBS.

  1. To analyze whether iTBS treatment can effectively reverse the cognitive deficits in patients with first-episode drug-free and remission schizophrenia;

  2. To further analyze whether iTBS treatment can reverse the intracortical inhibitory deficits in patients with first-episode drug-free and remission schizophrenia;

  3. Analyze whether the efficacy of iTBS in improving cognitive deficits is related to pre-treatment intracortical inhibition (SICI and LICI) in first-episode drug-free and remission schizophrenia patients; and whether the efficacy of iTBS is related to treatment interval and treatment The magnitude of the change in intracortical inhibition after the end correlates;

  4. Establish a predictive model for the early prediction of the efficacy of iTBS in improving cognitive deficits by E-I microcircuit function regulation susceptibility gene SNP and SICI and LICI indicators.

Connect with a study center

  • Shanghai Pudong New Area Mental Health Center

    Shanghai, Shanghai 200124
    China

    Active - Recruiting

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