A Clinical Trial of Adjunctive Thyroxine for Avolition in Schizophrenia

Inclusion Criteria: 1. Meet the diagnostic criteria for schizophrenia according to the International Classification of Diseases, 10th Revision (ICD-10) (World Health Organization, 1993); 2. Aged between 18 and 45 years, right-handed; 3. Currently clinically stable, with the primary antipsychotic medication formulation and dosage unchanged for at least 4 weeks, and a total PANSS score ≤ 60; 4. Predominant avolition symptoms, defined as a score ≥ 16 on the Motivation subscale of the Negative Symptom Assessment (NSA-15) (Zhou et al., 2023), with fewer than 3 items scoring ≥ 4 and fewer than 2 items scoring ≥ 5 on the PANSS positive subscale (Rabinowitz et al., 2013); 5. Receiving one or two second-generation antipsychotics (SGAs), with stable medication doses for at least 1 month; 6. Willingness and ability to maintain stable medication doses throughout the trial period; 7. Capacity to understand study procedures, cooperate with all testing requirements, and provide written informed consent. Exclusion Criteria: 1. Current treatment with clozapine or first-generation antipsychotics; 2. Current use of thyroid hormone medications or presence of thyroid dysfunction; 3. Hypersensitivity to levothyroxine sodium; or history of non-hypothyroid-related heart failure, tachyarrhythmias, or recent myocardial infarction; 4. Current use of medications known to interact with levothyroxine sodium that may affect its efficacy or safety (e.g., antidiabetic drugs, coumarin derivatives); 5. History of endocrinological or cardiovascular/cerebrovascular diseases; 6. IQ \< 80 assessed by the Chinese short-form Wechsler Adult Intelligence Scale (Gong, 1981); 7. History of substance abuse or drug addiction; 8. History of traumatic brain injury or neurological disorders; 9. Receiving electroconvulsive therapy (ECT) within the last 3 months; 10. Pregnancy, lactation, or planning pregnancy within the next 2 months (for female participants); 11. Claustrophobia; implanted metal devices (e.g., prosthetic implants, pacemakers); or other contraindications to MRI scanning.