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The Vitamins in Psychosis Study: A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Vitamins B12, B6, and Folic Acid on Symptoms and Neurocognition in First-Episode Psychosis

  • Kelly Allott
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Patrick D. McGorry
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Hok Pan Yuen
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Joseph Firth
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    NICM Health Research Institute, Western Sydney University, Sydney, New South Wales, Australia
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  • Tina-Marie Proffitt
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    School of Psychology, University of Waikato, Hamilton, Waikato, New Zealand
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  • Gregor Berger
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychiatric University Clinic, Zurich, Switzerland
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  • Paul Maruff
    Affiliations
    Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia
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  • Michaela K. O’Regan
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Alicia Papas
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Timothy C.B. Stephens
    Affiliations
    Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
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  • Colin P. O’Donnell
    Correspondence
    Address correspondence to Colin P. O’Donnell, M.D., Department of Psychiatry, Donegal Mental Health Service, Letterkenny University Hospital, Co. Donegal, Republic of Ireland.
    Affiliations
    Department of Psychiatry, Donegal Mental Health Service, Letterkenny University Hospital, Letterkenny, Donegal, Republic of Ireland
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      Abstract

      Background

      Elevated homocysteine is observed in schizophrenia and associated with illness severity. The aim of this study was to determine whether vitamins B12, B6, and folic acid lower homocysteine and improve symptomatology and neurocognition in first-episode psychosis. Whether baseline homocysteine, genetic variation, sex, and diagnosis interact with B-vitamin treatment on outcomes was also examined.

      Methods

      A randomized, double-blind, placebo-controlled trial was used. A total of 120 patients with first-episode psychosis were randomized to an adjunctive B-vitamin supplement (containing folic acid [5 mg], B12 [0.4 mg], and B6 [50 mg]) or placebo, taken once daily for 12 weeks. Coprimary outcomes were change in total symptomatology (Positive and Negative Syndrome Scale) and composite neurocognition. Secondary outcomes included additional measures of symptoms, neurocognition, functioning, tolerability, and safety.

      Results

      B-vitamin supplementation reduced homocysteine levels (p = .003, effect size = −0.65). B-vitamin supplementation had no significant effects on Positive and Negative Syndrome Scale total (p = .749) or composite neurocognition (p = .785). There were no significant group differences in secondary symptom domains. A significant group difference in the attention/vigilance domain (p = .024, effect size = 0.49) showed that the B-vitamin group remained stable and the placebo group declined in performance. In addition, 14% of the sample had elevated baseline homocysteine levels, which was associated with greater improvements in one measure of attention/vigilance following B-vitamin supplementation. Being female and having affective psychosis was associated with improved neurocognition in select domains following B-vitamin supplementation. Genetic variation did not influence B-vitamin treatment response.

      Conclusions

      While 12-week B-vitamin supplementation might not improve overall psychopathology and global neurocognition, it may have specific neuroprotective properties in attention/vigilance, particularly in patients with elevated homocysteine levels, patients with affective psychosis, and female patients. Results support a personalized medicine approach to vitamin supplementation in first-episode psychosis.

      Keywords

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      Linked Article

      • B Vitamin Supplements in First-Episode Psychosis: Some Neurodevelopmental and Physiologic Context
        Biological PsychiatryVol. 86Issue 1
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          Could an inexpensive, benign, and readily available intervention offer meaningful benefits for patients with serious mental illnesses (SMIs)? This question might be met with a reflexive skepticism among investigators in the field, for understandable reasons. Despite decades of research, standard drug therapies for schizophrenia and other SMIs remain inadequate, and simple remedies for such biologically complex disorders might seem implausible. Further, because our most ill patients often require some of the most toxic interventions in our arsenal (e.g., clozapine, lithium, or monoamine oxidase inhibitors), we may be conditioned to think, as through an algebraic property, that benign interventions will be the least effective.
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