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Personalized, Circuit-Based Transcranial Magnetic Stimulation for Highly Refractory Schizophrenia

Poster No:

Submission Type:

Abstract Submission

Authors:

Qiang Hua¹, Xiya Zhao², Weichao Tian², Hai Cao², Toongqing Huang², Wenqiang Xu², Kai Wang¹, Gong-Jun Ji²

Institutions:

¹Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ²School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui

First Author:

Qiang Hua
Department of Neurology, The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui

Co-Author(s):

Xiya Zhao
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Weichao Tian
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Hai Cao
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Toongqing Huang
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Wenqiang Xu
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Kai Wang
Department of Neurology, The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui

Gong-Jun Ji
School of Mental Health and Psychological Sciences, Anhui Medical University
Hefei, Anhui

Introduction:

Schizophrenia is one of the most severe mental illnesses. Despite advances in treatment, a subset of patients with highly refractory schizophrenia (HRS) continues to face limited treatment options for symptom relief. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a therapy for schizophrenia, though its clinical benefits were limited and inconsistent across studies. In current study, we calculate personalized rTMS targets based on a schizophrenia-specific circuit and assess its clinical efficacy in patients with HRS.

Methods:

The study was registered at ClinicalTrials.gov with the identifier NCT06732817. Patients meeting HRS criteria (disease duration exceeding six years, more than two hospitalizations, and an insufficient response to at least two antipsychotics) were prospectively recruited. Patients with HRS receive a 3-week personalized, schizophrenia circuit-based dual-target rTMS treatment, and collected structural and resting-state functional MRI data for each patient before treatment. A schematic of the trial design is shown in Fig. 1A.
The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total scores from baseline to week 3. Secondary outcomes included changes in the PANSS subscales, Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and Auditory Hallucination Rating Scale (AHRS) were also included as a secondary outcome.
The personalized dual targets in the left DLPFC and left TPJ were computed using a schizophrenia-specific circuit and each patient's rs-fMRI data. This schizophrenia-specific circuit, identified in our previous brain network mapping study, was associated with schizophrenia symptom remission (Wang Y, 2024, Schizophrenia Bulletin). We used this circuit as a seed map to compute its functional connectivity to every voxel in the patient's rs-fMRI data. The clusters with the strongest functional connectivity within the left DLPFC and TPJ masks were chosen as the two target sites, respectively (Fig 1B).

·Fig 1. Schematic of Trial Design and Personalized Target Calculation.

Results:

Twenty patients (17 women [85%]; mean [SD] age, 40.70 [10.56] years) completed three weeks of rTMS treatment. All patients were characterized by chronic, drug-resistant schizophrenia, with a mean [SD] disease duration of 13.13 [6.21] months, a mean [SD] of 5.10 [2.59] hospitalizations, and with a mean [SD] current olanzapine equivalent dosage of 21.46 [13.68] mg. Patients had been treated with an average of 3.35 [1.27] different antipsychotics before this study, without sufficient therapeutic responses.
The treatment was well-tolerated, with no serious adverse events occurring. There were significant reductions in PANSS total scores (t = 5.37, P <.0001; Fig 2A), PANSS positive scores (t = 3.99, P =.0008; Fig 2A), PANSS negative scores (P =.0009; Fig 2A), PANSS general scores (t = 4.59, P =.0002) after treatment. We also found significant improvements in AHRS scores (t = 2.35, P =.04), HAMA scores (P =.01), and HAMD scores (t = 2.67, P =.02). Additionally, we found that the reduction rates in PANSS total scores were significantly correlated with the disease duration (r =-0.55, P=.01; Fig 2B), suggesting shorter disease duration linked to better treatment benefits.

·Fig 2. Clinical Outcomes.

Conclusions:

Personalized, circuit-based, dual-target rTMS can effectively alleviate the symptoms of HRS without serious adverse events.

Brain Stimulation:

Non-invasive Magnetic/TMS ¹

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ²

Keywords:

MRI

Psychiatric

Schizophrenia

Transcranial Magnetic Stimulation (TMS)

Other - Highly refractory schizophrenia (HRS); Personalized; Schizophrenia-specific circuit; Dual target;

^1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was this research conducted in the United States?

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI

Structural MRI

TMS

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

SPM

Other, Please list - WhiteMatterSF; TMStarget

Provide references using APA citation style.

Wang, Y., Yang, Y., Xu, W., Yao, X., Xie, X., Zhang, L., Sun, J., Wang, L., Hua, Q., He, K., Tian, Y., Wang, K., & Ji, G. J. (2024). Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission. Schizophrenia bulletin, 50(3), 545–556. https://doi.org/10.1093/schbul/sbae003

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