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Univariate analysis To define the effect of drug exposure over 4 weeks and 8 weeks of treatment, linear mixed effects models (using the R package nlme 52 ) were fitted on each metabolite adjusting for age, gender, and HRSD 17 scores at baseline with subjects as random variable

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In the alternative pathway, StARD1, a mitochondrial cholesterol transporter, and CYP27A1 limit mitochondrial oxysterol synthesis

It is important to note that B12 levels should ideally be measured before commencing replacement therapy, as supplementation rapidly normalises biochemical markers, potentially obscuring the diagnosis