Transcranial Sonography and Machine Learning for Schizophrenia Identification (TCS-ML-SZ)

Development and Validation of an Early Prediction Model for Schizophrenia Integrating Transcranial Sonography Structural Imaging and Machine Learning

Schizophrenia is a serious mental illness. Doctors usually diagnose schizophrenia by talking with patients, reviewing symptoms, and using clinical assessment. In early or less typical cases, diagnosis may be difficult.

This study will look at whether brain ultrasound information can help doctors identify features related to schizophrenia. The ultrasound scan used in this study is called transcranial sonography. It is a non-invasive scan that uses sound waves to look at brain structures through natural thin areas of the skull.

The study will include adults with schizophrenia and adults without a personal or family history of mental disorders. All participants will have a transcranial sonography scan and provide basic clinical information. The researchers will measure brain ultrasound features, including the substantia nigra, raphe nuclei, and third ventricle, and will combine these features with clinical information.

The main question is whether a computer model using ultrasound and clinical information can help distinguish adults with schizophrenia from adults without schizophrenia. The model is intended only as a research tool and possible future aid for doctors. It will not replace diagnosis by a psychiatrist and will not change the participant's usual medical care.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Diagnostic test: Transcranial Sonography

Detailed Description

This is a prospective observational case-control study designed to develop and evaluate a machine-learning model for identifying schizophrenia using transcranial sonography (TCS) structural imaging features and clinical information.

Schizophrenia is clinically heterogeneous, and diagnosis depends mainly on clinical symptoms and psychiatric assessment. TCS is a non-invasive imaging method that can assess selected deep brain structures through the temporal acoustic window. Previous studies suggest that ultrasound features of structures such as the substantia nigra, raphe nuclei, and third ventricle may be related to neuropsychiatric disorders. This study will investigate whether TCS-derived structural imaging features, combined with clinical variables, can support auxiliary identification of schizophrenia.

Adults aged 18 to 65 years with schizophrenia diagnosed according to ICD-10 criteria and matched adults without a personal or family history of psychiatric disorders will be enrolled. The planned enrollment is 200 participants, including approximately 100 participants with schizophrenia and 100 healthy controls. Participants will undergo baseline TCS assessment and clinical data collection. No therapeutic intervention will be assigned by the investigators, and participation will not replace or alter usual clinical care.

TCS assessments will focus on selected brain structural imaging features, including substantia nigra echogenicity, raphe nuclei echogenicity, and third-ventricle width. Clinical information may include demographic characteristics, medical history, family history, disease course, medication history, and symptom assessment data when available. TCS measurements will be performed according to a standardized procedure, and image quality control will be conducted to reduce measurement variability.

The collected TCS and clinical variables will be integrated into a structured dataset for model development. Candidate machine-learning methods may include logistic regression, random forest, support vector machine, and XGBoost. Feature selection and model optimization will be performed within the model development process. Internal validation will be used to assess model performance, and additional independent data may be used for external validation if available.

Model performance will be evaluated using discrimination, calibration, and clinical utility metrics, including the area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, F1 score, calibration assessment, and decision curve analysis where appropriate. Model interpretability will be explored using SHAP to assess the relative contribution of TCS imaging features and clinical variables.

The resulting model is intended as an auxiliary research tool for schizophrenia identification. It is not intended to make a definitive diagnosis, replace psychiatric assessment, or guide treatment decisions independently.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Xiaochen Zhang; Phone Number: +8615967690053; Email: 15967690053@163.com

Study Locations

• China
  • Zhejiang
    • Taizhou, Zhejiang, China, 317200
      • Taizhou Second People's Hospital
      • Contact: Xiaochen Zhang; Phone Number: +8615967690053; Email: 15967690053@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 to 65 years will be recruited from Taizhou Second People's Hospital and related recruitment channels. The study population will include participants with schizophrenia diagnosed according to ICD-10 criteria and healthy control participants without a personal or family history of psychiatric disorders. Healthy controls will be matched as far as possible to the schizophrenia group by basic demographic characteristics. All participants will undergo baseline transcranial sonography assessment and clinical data collection.

Description

Inclusion Criteria:

Schizophrenia group:

1. Adults aged 18 to 65 years.
2. Diagnosis of schizophrenia according to ICD-10 criteria by a psychiatrist.
3. Able to complete clinical assessment and transcranial sonography examination.
4. No other severe physical disease, neurological disease, or major psychiatric disorder.
5. Written informed consent provided by the participant or legally authorized representative.

Healthy control group:

1. Adults aged 18 to 65 years.
2. No personal history of psychiatric disorders.
3. No family history of psychiatric disorders.
4. No severe physical disease, neurological disease, or major psychiatric disorder.
5. Basic demographic characteristics matched as far as possible to the schizophrenia group.
6. Able to complete clinical assessment and transcranial sonography examination.
7. Written informed consent provided by the participant or legally authorized representative.

Exclusion Criteria:

1. Severe physical disease or neurological disease.
2. History of drug or alcohol abuse.
3. Inability to complete clinical assessment or transcranial sonography examination.
4. Inadequate temporal acoustic window or poor image quality preventing valid transcranial sonography measurements.
5. Acute or clinically unstable state that prevents completion of study procedures.
6. Comorbid major psychiatric disorder, such as major depressive disorder.
7. Refusal or withdrawal of informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Schizophrenia Group; Adults aged 18 to 65 years with schizophrenia diagnosed according to ICD-10 criteria. Participants will undergo baseline transcranial sonography assessment and clinical data collection.	Diagnostic test: Transcranial Sonography; Baseline transcranial sonography assessment of brain structural imaging features, including substantia nigra echogenicity, raphe nuclei echogenicity, and third-ventricle width.
Healthy Control Group; Adults aged 18 to 65 years without a personal or family history of psychiatric disorders and matched as far as possible to the schizophrenia group by basic demographic characteristics. Participants will undergo baseline transcranial sonography assessment and clinical data collection.	Diagnostic test: Transcranial Sonography; Baseline transcranial sonography assessment of brain structural imaging features, including substantia nigra echogenicity, raphe nuclei echogenicity, and third-ventricle width.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the ROC Curve of the Final TCS-Clinical Model	The area under the receiver operating characteristic curve will be used to assess the ability of the final machine-learning model, based on transcranial sonography and clinical variables, to distinguish participants with ICD-10 schizophrenia from healthy controls. The reference standard will be clinical diagnosis according to ICD-10 criteria.	Baseline; analyzed after completion of baseline data collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of the Final TCS-Clinical Model	Sensitivity and specificity will be calculated for the final model for distinguishing participants with schizophrenia from healthy controls, using a pre-specified or internally optimized classification threshold.	Baseline; analyzed after completion of baseline data collection
Other Classification Performance Metrics of the Final Model	Accuracy, precision, recall, and F1 score will be calculated to further evaluate the classification performance of the final model for distinguishing participants with schizophrenia from healthy controls.	Baseline; analyzed after completion of baseline data collection
Calibration Performance of the Final TCS-Clinical Model	Calibration will be evaluated by comparing predicted probabilities with observed diagnostic status using calibration plots, calibration slope, calibration intercept, and/or Brier score, as appropriate.	Baseline; analyzed after completion of baseline data collection

Collaborators and Investigators

• Sponsor: Taizhou Second People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 17, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Machine Learning; Case-Control Study; Diagnostic Model; Transcranial Sonography; Schizophrenia Identification; Substantia Nigra; Raphe Nuclei; Brain Ultrasound
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Neurological; Radiography; Ultrasonography; Echoencephalography; Neuroradiography; Neuroimaging; Ultrasonography, Doppler; Ultrasonography, Doppler, Transcranial
• Other Study ID Numbers: 25YWB115; TZEY-EC-2026-05 (Other Identifier: Ethics Committee of Taizhou Second People's Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data generated or analyzed during this study will not be publicly shared because of participant privacy, the sensitive nature of psychiatric clinical data, and restrictions in the ethics approval and informed consent. Aggregated results will be reported in the published article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No