Background: Schizophrenia is a serious mental illness. The diagnosis and severity evaluations of schizophrenia are generally based on patient behaviors. Biomarkers are objectively measured and used as indicators for diagnosis confirmation, symptom assessment, and evaluation of pharmacologic responses to therapeutic interventions. Neuroendocrine and metabolite substrates are potential biomarkers of the pathogenic processes in schizophrenia.

Aims: The aims of this study are to determine (a) the differences in neuroendocrine and metabolite substrates between patients diagnosed with schizophrenia and healthy controls; and (b) the associations among the neuroendocrine and metabolite substrates, cognitive function, clinical symptoms, and treatment responses of patients diagnosed with schizophrenia.

Methods: (a) The investigators plan to recruit 100 patients diagnosed with schizophrenia and 100 healthy controls as participants. (b) At the baseline and Week 12, patient blood samples will be obtained to measure the levels of neuroendocrine substrates and metabolite markers. Clinical symptoms and cognitive function will be evaluated. (c) For the healthy control participants, blood samples will be obtained once to measure neuroendocrine and metabolite marker levels.

Expected Results: The results of this study may contribute to identifying potential neuroendocrine and metabolite biomarkers of schizophrenia, and clarify the associations among the neuroendocrine and metabolite substrates, cognitive function, clinical symptoms, and treatment responses of patients diagnosed with schizophrenia. Such information is crucial for clinical evaluations and future research.

1. The investigators plan to recruit 100 patients with schizophrenia and 100 healthy control subjects.
2. For the patients, diagnoses of schizophrenia will be confirmed using the Chinese version of the Mini International Neuropsychiatric Interview (MINI). At the baseline and Week 12, patient blood samples will be obtained to measure the levels of neuroendocrine substrates (didehydroepiandrosterone, dehydroepiandrosterone sulfate, pregnenolone, and cortisol) and metabolite markers (lipid profiles, glycerate, eicosenoic acid, pyruvate, b-hydroxybutyrate, Cysteine). Cognitive function will be evaluated using the Brief Assessment of Cognition in Schizophrenia. The participants' clinical symptoms and daily activities will be assessed using the Positive and Negative Syndrome Scale, 17-item Hamilton Depression Rating Scale, and Personal and Social Performance Scale.
3. For the healthy control subjects, psychiatric diagnoses will be verified using MINI, and blood samples will be obtained once to measure neuroendocrine and metabolite marker levels.

Patients with Schizophrenia

Inclusion criteria:

1. Diagnosed with schizophrenia and will be confirmed using the Chinese version of the Mini International Neuropsychiatric Interview (MINI).
2. Age between 18 to 79.
3. Have signed the informed consent.

Exclusion criteria:

1. Having history of illicit drug use or other major psychiatric disorders (e.g., bipolar disorder, major depressive disorder, or organic mental disorders).

Healthy Controls

Inclusion criteria:

1. Psychiatric diagnosis without schizophrenia will be confirmed using the Chinese version of MINI.
2. Age between 18 to 79.
3. Have signed the informed consent.

Exclusion criteria:

1. Having history of illicit drug use or other major psychiatric disorders (e.g., psychosis, bipolar disorder, major depressive disorder, or organic mental disorders).

1. Patients with schizophrenia will be recruited from the out-patient department in Kaohsiung Chang Gung Memorial Hospital, Kaohsiung city, Taiwan
2. Healthy controls will be recruited from the staff in Kaohsiung Chang Gung Memorial Hospital and from the communities in Kaohsiung city, Taiwan