Assessing the effects of coenzyme QIO in schizophrenia & schizoaffective disorder: a randomised, placebo controlled trial
Citation:
MAGUIRE, ÁINE, Assessing the effects of coenzyme QIO in schizophrenia & schizoaffective disorder: a randomised, placebo controlled trial, Trinity College Dublin.School of Medicine, 2020Download Item:
Abstract:
Background: Schizophrenia is a complex, heterogeneous, neurodevelopmental disorder. Cognitive impairments and negative symptoms such as avolition and asociality are prevalent in the majority of patients with a diagnosis of schizophrenia. They are considered a major source of disability and strongly associated with functional and psychosocial outcomes, as well as ability to engage with psychological interventions. While anti-psychotic medication is typically a mainstay treatment for positive symptoms, there are few widely accessible and low-cost therapies for the remaining features available. Further, there has been a shift towards interventions which not only target symptoms or impairments, but also enhance quality of life and overall functioning. Thus alternative interventions to support people living with schizophrenia, including those which enhance cognition and reduce negative symptoms are receiving increasing attention. One encouraging line of enquiry in the development of effective interventions is based on the hypothesis that the symptoms of schizophrenia, particularly affective and negative symptoms and cognitive impairments are related to mitochondrial function. Coenzyme Q10 (CoQ10) is an endogenous compound that is essential for energy production within the mitochondria, but also functions as a potent anti-oxidant, inhibiting oxidative stress and damage. However, endogenous levels of CoQ10 can decline due to genetic and environmental factors, and associated mitochondrial impairment. Often deficits of CoQ10 are associated with fatigue, myopathy, and cognitive impairment. In light of its many functions, CoQ10 supplementation to minimise decline and improve symptoms has been investigated in multiple disorders associated with mitochondrial dysfunction, including neurological and neuropsychiatric disorders. This thesis investigated the potential role of CoQ10 supplementation in schizophrenia and schizoaffective disorder.
Aims and structure of thesis: The primary aim of this thesis was to examine the potential effect of CoQ10 supplementation on 1) cognitive function and 2) psychological and physical health in schizophrenia. A double-blind, randomised, placebo-controlled trial (RCT) was conducted to assess the effects of CoQ10 supplementation (300mg/day) on the pre-specified primary outcomes of attention and working memory performance after 3 and 6 months of supplementation. Secondary cognitive outcomes were: processing speed, executive function, and estimated current IQ. Secondary psychological symptom outcomes were depression, anxiety, and negative symptoms: avolition, asociality, blunted affect and alogia. Secondary health-related outcomes were: energy, diastolic and systolic blood pressure, physical activity, quality of life, and functional status. Secondary biochemical outcomes were CoQ10 status and mitochondrial function. Chapter 1 discusses findings in the literature supporting the use of CoQ10 supplementation in neurological and neuropsychiatric disorders. Chapter 2 describes the methods employed during the RCT. Methodological issues that presented during the conduct of the RCT and influenced subsequent analyses and interpretation of findings are discussed in Chapter 3. Chapter 4 outlines the results of CoQ10 supplementation on primary and secondary cognitive outcomes. Chapter 5 outlines the results of CoQ10 supplementation on secondary outcomes: CoQ10 levels, mitochondrial function, energy, psychological, and health-related outcomes. Finally, Chapter 6 presents a general discussion of the findings.
Results: In total 70 patients with a diagnosis of schizophrenia and schizoaffective disorders were randomised to the CoQ10 (300mg/day) and placebo intervention groups. The effects of CoQ10 supplementation were compared to placebo at 3 and 6 months on primary and secondary outcomes. The primary analysis of outcomes was based on complete cases for each outcome variable. Sensitivity analysis followed an Intention to Treat (ITT) approach that used multiple imputations to account for missing values. Overall, there was no effect of CoQ10 supplementation on the primary or secondary cognitive outcome measures at either time point. This is despite observing an increase in plasma CoQ10 concentration at 3 months in the CoQ10 group compared to placebo, a comparative plasma increase which subsequently disappeared at 6 month analysis. Further CoQ10 supplementation also had no effect on mitochondrial function (plasma lactate concentration), energy, psychological and health-related outcomes outcome measures at either time point. Post-hoc secondary analyses including only patients who fully adhered to assigned intervention and those who remained on the same concomitant medication throughout the study also showed no effect of CoQ10.
Conclusion: While a number of limitations including modest sample size, attrition, and adherence may reduce estimates of effect, the results of the study indicate that CoQ10 supplementation confers minimal benefit on cognitive, energy, psychological and health-related outcomes in schizophrenia and schizoaffective disorder. It appears likely that the non-significant findings related to an absence of CoQ10 deficit within schizophrenia.
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Trinity College Dublin (TCD)
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https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:AFMAGUIRDescription:
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Author: MAGUIRE, ÁINE
Advisor:
Gill, MichaelPublisher:
Trinity College Dublin. School of Medicine. Discipline of PsychiatryType of material:
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