MitoQ for improving cognition in early course psychosis illnesses

This 12-week double-blind, randomized, placebo-controlled trial aims to assess the effect of MitoQ on neurocognition, psychiatric symptoms, functioning, and exosomal biomarkers (miR-137 and COX6A2) in individuals with early-phase schizophrenia-spectrum disorders (E-SSD). Conducted at Yale University and McLean Hospital/Harvard Medical School, the study will involve 50 participants at Yale, stratified into high risk (HR) and low risk (LR) groups based on mitochondrial dysfunction markers. The primary objective is to evaluate changes in global cognition using the MATRICS Consensus Cognitive Battery (MCCB). Secondary objectives include assessing changes in clinical outcomes (GAF, SOFAS, PANSS) and blood biomarkers. The hypothesis is that MitoQ will improve cognitive function, particularly in the HR subgroup with mitochondrial dysfunction.

Inclusion Criteria:

• Male or female aged 18 to 35 years old
• Patients who have been diagnosed with one of the following schizophrenia-spectrum disorders: schizophreniform disorder, schizophrenia, schizoaffective disorder, unspecified psychosis.
• Less than five years in treatment for psychosis (note that the duration of psychosis may be longer than 5 years, but this is more difficult to ascertain and therefore less reliable as an inclusion criterion).
• PANSS score < 75
• Ability to provide informed consent.

Exclusion Criteria:

• Meeting DSM-5 criteria for any substance use disorder diagnosis in the past 6 months will be exclusionary EXCEPT tobacco and mild/moderate cannabis use disorder, which will be included
• Any acute medical condition requiring actively changing treatment (e.g., autoimmune disorders, acute infections, HIV/AIDS, cancer, renal failure, hepatic dysfunction, cardiovascular disease, or abnormal thyroid findings). Individuals with chronic medical conditions that are stable will not be excluded (e.g., person with hypothyroidism who is taking thyroid hormone replacement and has TSH levels within the normal range; person with well-managed diabetes; etc.)
• Epilepsy or another seizure disorder
• Intellectual disability (e.g., history of IQ < 70).
• Under legal guardianship
• Not English speaking. The questionnaires, instruments, cognitive assessments used in this research study have not been translated, validated, or studied extensively in non-English-speaking individuals. For this reason, we will not enroll individuals who do not speak English to maintain validity in the study.
• MitoQ allergy
• Treatment with antioxidants: omega3 (fish oil), Vitamin E, Vitamin C, multivitamins, NAC (N-acetyl cysteine) within the last 14 days. If the treatment is taken without prescription, we will ask the patient to stop using it for at least 14 days to become eligible for the present study.
• Children and adolescents, pregnant women, women who have the intention to become pregnant during the course of the study, and breastfeeding women are excluded from the study. This is because no MitoQ pharmacokinetic data are available in pediatric populations, pregnancy or breastfeeding.
• Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of childbearing potential.
• Enrollment of study staff, their family members, and other dependent persons