Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression.
ABSTRACT In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels and clinical response in patients with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week, double-blind trial of either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine.
Fifty-five outpatients (mean +/- SD age = 41.7 +/- 10.6 years; 50.9% women) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to fluoxetine treatment initiation). Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of a logistic regression, we then assessed the relationship between (1) low or normal folate levels, (2) normal or low B12 levels, and (3) elevated or normal homocysteine levels and clinical response to double-blind treatment. The study was conducted from November 1992 to January 1999.
Low serum folate levels (chi2=3.626, p =.04), but not elevated homocysteine (p >.05) or low vitamin B12 levels (p >.05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7.1% versus 44.7%, respectively.
Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD.
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ABSTRACT: Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/- hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 08/2008; 28(28):7219-30. DOI:10.1523/JNEUROSCI.0940-08.2008 · 6.75 Impact Factor
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ABSTRACT: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.Journal of Psychopharmacology 07/2008; 22(4):343-96. DOI:10.1177/0269881107088441 · 2.81 Impact Factor
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ABSTRACT: Summary Depression in adolescence is associated with a range of negative outcomes and substantial risk for morbidity and mortality across the lifespan. Dietary improvement and supplementation may offer an inexpensive and acceptable adjunct to standard treatment; yet this has, to date, been largely overlooked, owing to lack of evidence and knowledge. This is important, as improving understanding of the role of diet in mental health and promotion of appropriate dietary practices could significantly reduce the personal and social impact of depression in young people. This article sets out to review the existing research literature on associations between diet and mental health in adolescence, in particular, the role of diet in the prevention and management of adolescent depression. A closer examination of associations between obesity and depression is also included, as these two conditions often co-occur. Research into diet and mental health tends to fall into two main categories: population-based observational studies and intervention studies; however, there is very little research evidence specific to adolescents. Potential implications for mental healthcare policy and practice are discussed.Nutrition Bulletin 02/2007; 32(s1):90 - 99. DOI:10.1111/j.1467-3010.2007.00608.x