The goal of this clinical trial is to investigate whether adjunctive thyroxine treatment can ameliorate motivation deficits in adults with schizophrenia experiencing predominant avolition (core negative symptom).

The main questions it aims to answer are:

• Does adjunctive thyroxine reduce avolition symptoms compared to placebo?
• Does adjunctive thyroxine normalize cortico-striatal circuit activity during reward processing?

Researchers will compare the treatment group (adjunctive sodium tablets, 50μg/day) with the control group (dose-equivalent placebo starch tablet) to see if thyroid hormone:

1. Significantly improves clinical scores of avolition
2. Modulates neural activation in motivation-processing brain circuits

Participants will:

• Maintain stable antipsychotic therapy for 8 weeks
• Receive daily levothyroxine/placebo tablets
• Complete the following assessments pre-/post-treatment:
• Clinical evaluations (PANSS, NSA, PSP)
• MRI scans (resting-state, structural, fMRI during reward tasks)
• Blood tests
• Behavioral motivation tasks

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.