PQQ for Cognitive and Negative Symptoms

Inclusion criteria

Eligible male and female patients aged 18 to 50 years, diagnosed with schizophrenia according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5), will be included in the study. Participants are required to meet the following criteria: a Positive and Negative Syndrome Scale (PANSS) total scores of ≥ 60 (indicating an active phase of the illness), a PANSS negative subscale scores of ≥ 20, and a duration of illness of at least 2 years (indicating chronic schizophrenia). Additionally, participants must have been on a stable dose of antipsychotic medication for a minimum of 6 weeks prior to enrollment, and the use of antioxidants or anti-inflammatory medications is prohibited within 2 weeks preceding enrollment.

Exclusion criteria

Patients with comorbid psychiatric disorders as defined by the DSM-5, such as substance abuse or dependence (excluding nicotine), or intellectual disability (IQ < 70); those with significant depressive symptoms, defined as a score ≥14 on the 17-item Hamilton Depression Rating Scale (HAMD-17) or ≥ 4 on the depression item of PANSS; individuals with severe medical or neurological conditions, or those unable to communicate effectively; patients with a known allergy to PQQ disodium salt, or who are pregnant, breastfeeding, or have severe hepatic or renal impairment; women of childbearing potential who are not using reliable contraception; patients who have received modified electroconvulsive therapy (MECT) or other physical treatments within six months prior to enrollment; and those currently receiving treatments that cannot be discontinued, including antidepressants, mood stabilizers, antihistamines, or combination therapy with two or more antipsychotics (except for low-dose aripiprazole, ≤ 5 mg/day, used solely for prolactin reduction).

Additional exclusion criteria for participants undergoing fMRI scanning:

Participants are required to complete a comprehensive safety questionnaire addressing potential risks associated with exposure to a 3-Tesla magnetic field and the MRI environment. MRI-specific exclusion criteria include: the presence of MRI-incompatible implants (e.g., cochlear implants, insulin pumps, pacemakers, or other metallic implants); a history of possible intraocular metallic foreign bodies due to manual labor without appropriate eye protection; tattoos containing red pigments; claustrophobia; or unwillingness to be informed of any incidental structural brain abnormalities detected during the scan.