No Effect of Coenzyme Q10 on Cognitive Function, Psychological Symptoms, and Health-related Outcomes in Schizophrenia and Schizoaffective Disorder: Results of a Randomized, Placebo-Controlled Trial.

BACKGROUND: Cognitive impairments, negative symptoms, affective symptoms, and low energy are highly prevalent features of schizophrenia. Mitochondrial dysfunction has been hypothesized as one of the numerous factors to underlie the manifestation of these symptoms. The objective of this study was to evaluate whether Coenzyme Q10 (CoQ10) has a role in the treatment of schizophrenia and schizoaffective disorder. METHODS: A double-blind, randomized, placebo-controlled trial was conducted to assess the effects of CoQ10 supplementation (300 mg/day) on the co-primary outcomes of attention and working memory performance after 3 and 6 months. Secondary outcomes included plasma CoQ10 levels, mitochondrial function, energy, depression, anxiety, negative symptoms, and quality oflife. FINDINGS: In total, 72 patients were randomized to intervention groups. Overall, there was no effect of CoQ10 supplementation on the primary outcome measures at 3 or 6 months. Further, with the exception of plasma CoQ10 levels, CoQ10 supplementation also had no effect on the secondary outcomes. At 3 months, CoQ10 concentration was significantly higher in the CoQ10 group (3.85 µg/mL) compared with placebo (1.13 µg/mL); this difference was not present at 6 months. CONCLUSIONS: The results of the study suggest that CoQ10 supplementation at 300 mg/day for 6 months is unlikely to be beneficial for cognitive, psychological and health-related outcomes in schizophrenia and schizoaffective disorder. However, a number of limitations including low adherence, modest sample size, and attrition, likely reduce estimates of effects. As such, results should be considered preliminary.

Prevalence of N-Methyl-d-Aspartate Receptor antibody (NMDAR-Ab) encephalitis in patients with first episode psychosis and treatment resistant schizophrenia on clozapine, a population based study.

INTRODUCTION: N-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis consensus criteria has recently been defined. We aimed to examine the prevalence of NMDAR-Ab encephalitis in patients with first episode psychosis (FEP) and treatment resistant schizophrenia (TRS) on clozapine, using clinical investigations, antibody testing and to retrospectively apply diagnostic consensus criteria. METHODS: Adult (18-65 years old) cases of FEP meeting inclusion criteria were recruited over three years and assessed using the Structured Clinical Interview for DSM-IV disorders (SCID). NMDAR-Ab was identified using a live cell-based assay (L-CBA). Seropositive cases were clinically investigated for features of encephalitis including neuro-imaging, EEG and CSF where possible. Serum was retested using immunohistochemistry (IHC) as part of diagnostic criteria guidelines. A cohort of patients with TRS was also recruited. RESULTS: 112 FEP patients were recruited over 3 years. NMDAR-Ab seroprevalence was 4/112 (3.5%) cases. One case (<1%) was diagnosed with definite NMDAR-Ab encephalitis and treated with immunotherapy. One of the three other seropositive cases met criteria for probable encephalitis. However all three were ultimately diagnosed with mood disorders with psychotic features. None have developed neurological features at three year follow up. 1/100 (1%) of patients with TRS was 100 patients with TRS were recruited. One case (1%) seropositive for NMDAR-Ab but did not meet criteria for encephalitis. CONCLUSIONS: NMDAR-Ab encephalitis as defined by consensus guidelines occured rarely in psychiatric services in this study. Further studies are needed to establish pathogenicity of serum NMDAR-Ab antibodies. Psychiatric services should be aware of the clinical features of encephalitis.

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study.

BACKGROUND: Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia. AIMS: To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort. METHOD: Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479). RESULTS: In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16-34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58-14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28-19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9-86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0-100.0%) for the replication cohort. CONCLUSIONS: These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.