Folic acid and psychopathology

https://doi.org/10.1016/0278-5846(89)90037-7Get rights and content

Abstract

  • 1.

    1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia.

  • 2.

    2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms.

  • 3.

    3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels.

  • 4.

    4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients.

  • 5.

    5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15–20 mg/day) are known to be toxic and to cause mental symptoms.

  • 6.

    6. Two placebo-controlled studies have demonstrated beneficial effects of Folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day.

  • 7.

    7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxy-tryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT.

  • 8.

    8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency.

  • 9.

    9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms.

  • 10.

    10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.

References (76)

  • L.A. Ordonez et al.

    Folic acid deficiency and methyl group metabolism in rat brain: effects of L-dopa

    Arch. Biochem. Biophys.

    (1974)
  • A.J. Ralston et al.

    Effects of folic acid on fit-frequency and behaviour in epileptics on anticonvulsants

    Lancet

    (1970)
  • E.H. Reynolds

    Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients

    Lancet

    (1967)
  • E.H. Reynolds

    Anticonvulsants, folic acid, and epilepsy

    Lancet

    (1973)
  • E.H. Reynolds et al.

    Neuropsychiatric aspects of anticonvulsant megaloblastlc anaemia

    Lancet

    (1968)
  • E.H. Reynolds et al.

    Folic acid and anticonvulsants

    Lancet

    (1969)
  • E.H. Reynolds et al.

    Methylation and mood

    Lancet

    (1984)
  • W.E. Thornton

    Folate deficiency in Puerperal psychosis

    Am. J. Obstet. Gynecol.

    (1977)
  • A.J. Turner

    The roles of folate and pteridine derivatives in neurotransmitter metabolism

    Biochem. Pharmacol.

    (1977)
  • M.T. Abou-Saleh et al.

    Folate deficiency in dementia

    Brit. J. Psychiatry

    (1986)
  • M.J. Bober

    Senile dementia and nutrition

    Brit. Med. J.

    (1984)
  • M.I. Botez et al.

    Neurophysiological correlates of folic acid deficiency: facts and hypotheses

  • M.L. Botez et al.

    Folate deficiency and decreased brain 5-hydroxytryptamine synthesis in man and rat

    Nature

    (1979)
  • M.I. Botez et al.

    The effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid

    Ann. Neurol.

    (1982)
  • M.I. Botez et al.

    The Wechsler subtests in mild organic brain damage associated with folate deficiency

    Psychol. Med.

    (1984)
  • T. Bottiglieri et al.

    Folate status in psychiatric patients: relationship with CSF neurotransmitter metabolites

  • N. Callaghan et al.

    The relationship of serum folic acid and vitamin B12 levels to psychosis in epilepsy

    Irish J. Med. Sci.

    (1969)
  • M.W.P. Carney

    Serum folate values in 423 psychiatric patients

    Br. Med. J.

    (1967)
  • M.W.P. Carney

    Folate-responsive schizophrenia

    Lancet

    (1975)
  • M.W.P. Carney

    Neuropharmacology of S-adenosyl methionine

    Clin. Neuropharmacol.

    (1986)
  • M.W.P. Carney et al.

    Associations of subnormal serum folate and vitamin B12 values and effects of replacement therapy

    J. Nerv. Ment. Dis.

    (1970)
  • M.W.P. Carney et al.

    Serum folic acid and B12 in 272 psychiatric inpatients

    Psychol. Med.

    (1978)
  • N. Colman et al.

    Dietary assessments with special emphasis on prevention of folate deficiency

  • A. Coppen et al.

    Plasma folate and affective morbidity during longterm lithium therpay

    Br. J. Psychiat.

    (1982)
  • T. Del Ser Quijano et al.

    Psychological disturbances and folic acid in chronic epileptic outpatients

    Epilepsia

    (1983)
  • L. Elsborg

    Inhibition of intestinal absorption of folic acid by phenytoin

    Acta Haematol.

    (1974)
  • J.M. Freeman et al.

    Folate-responsive homocystinuria and “schizophrenia”. A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity

    New Engl. J. Med.

    (1975)
  • J.S. Goodwin et al.

    Association between nutritional status and cognitive functioning in a healthy elderly population

    J. Amer. Med. Assoc.

    (1983)
  • Cited by (0)

    View full text