MitoQ for Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction

The planned clinical trial aims to test the effect of an oral administration of MitoQ on neurocognition, psychiatric symptoms, functioning, and exosomal levels of the mechanism-based biomarkers miR-137 and COX6A2 in HR individuals in the early phase of schizophrenia-spectrum disorders (E-SSD). The investigators propose to implement a randomized, double-blind, placebo-controlled stratified clinical trial with MitoQ as an adjunctive treatment for 12 weeks in a sample of n=25 patients with early-stage psychosis. The primary outcome will be a change in global cognition as defined by the MATRICS Consensus Cognitive Battery (MCCB). Specifically, the hypothesis is that MitoQ will lead to an increase in the MCCB cognitive composite score in the subgroup of early psychosis patients displaying peripheral markers of mitochondrial dysfunction. To test whether the oral administration of MitoQ will improve neurocognition in the HR subgroup, the investigators will conduct a double-blind, randomized, placebo-controlled trial at two sites (McLean Hospital and Yale School of Medicine). The overall goal of the study is to assess 100 patients (50 per site) with early phase psychotic disorders for HR status (with a blood test) and randomize 50 HR patients (25 per site). This 50% proportion is based on the fact that, in the Early psychosis Lausanne Cohort, the HR patients constitute half of the entire cohort 1. The two sites will conduct research procedures in parallel, following the same protocol, but undergo independent processes of human subjects review and oversight by each site's local institutional review board. Thus, at McLean (for which the Mass General Brigham IRB will serve as the IRB of record), the investigators plan to assess 50 early psychosis patients for HR status and randomize 25 HR patients to MitoQ vs. placebo. An equivalent number of participants will be enrolled and randomized at Yale (for which the Yale IRB will serve as the IRB of record). With 20% attrition, it is expected that there will be 20 completers per site at the end of the study. Patients will be asked to take part in a clinical trial consisting of a randomization to either MitoQ or placebo for 12-weeks and a follow up visit 4 weeks after the end of the last intervention. Patients who are in the first 5 years of treatment for a SCZ-spectrum disorder will be eligible 30. All eligible patients with an early phase psychotic disorder will be recruited for this study. Patients who enroll in the study will undergo a blood test during the screening visit to determine if their plasma mIR137 and COX6A2 levels are consistent with high risk (HR) or low risk (LR) status. Once this categorization has been made, only HR patients will be invited to proceed with the study. HR patients who wish to continue will be assigned randomly to either the MitoQ or the placebo arm. Primary outcome: \- Our primary outcome is change in cognitive function, as measured by change in the composite MCCB score from baseline to 12 weeks. Secondary outcomes: * The investigators will also measure each specific neurocognitive domain within the MCCB because each domain includes differential information. For example, attention/vigilance appears to best differentiate HR from LR patients. * The investigators will also include change in clinical outcomes and blood biomarkers as described in the sections below: 1. Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) 2. Positive and negative symptoms (Positive and Negative Syndrome Scale- PANSS) 3. Blood biomarkers: Improvement/normalization of the exosomal levels of miR-137 and COX6A2 to demonstrate target engagement. 4. Clinical global impression (CGI) score: Change in global illness severity, measured with the Clinical Global Impressions-Severity (CGI-S). Safety Outcomes: All adverse effects, vital signs, ED visits and hospitalizations, and the Generic assessment of side effects scale (GASE-D) score will be recorded at every visit. There will also be an EKG obtained at the screening visit, at the start of treatment (week 0), and at week 12.