Psychiatry and Clinical Psychopharmacology

Mechanisms of fish oil (Omega-3 fatty acids), vitamin B12, folate and other add-on treatments in psychiatric disorders

Psychiatry and Clinical Psychopharmacology 2011; 21: -
Read: 971 Published: 23 March 2021

The need for new treatments has led several investigators to examine the potential role of omega-3 fatty acids, found in marine and plant sources, in the treatment of psychiatric disorders. Omega-3 fatty acids are associated with normal brain development, neuronal plasticity, and function (1). Cell biology and molecular studies suggest that omega-3 fatty acids modulate membrane şuidity and dopaminergic and serotonergic neurotransmission (2). It has been observed that omega-3 fatty acids have effects on the phospholipid cell membrane and the secondary messenger system similar to mood stabilizing drugs like lithium (3). It has been also demonstrated by recent studies that add-on treatments with omega-3 fatty acids in mood disorders significantly improved the symptoms. Another way to investigate the effects of omega-3 fatty acids is by estimating the regional brain concentrations of various metabolites with proton magnetic resonance spectroscopy (PMRS). In a study that used this method in a population with first-episode psychosis, improvement of the negative symptoms of the patients were observed parallel to the increase in glutathione availability and modulation of the glutamine/glutamate cycle with ethyl-eicosapenthaenoic acid augmentation treatment (4). Post-mortem polyunsaturated fatty acid concentrations in the prefrontal areas of antipsychotic-naive schizophrenia patients were found to be lower than those of schizophrenia patients treated with atypical antipsychotics. Additionally, in an animal study, increases in the omega-3 fatty acid concentration in erythrocytes and prefrontal cortex were observed after long-term treatment with risperidone.

One of the earliest reports about the possible psychiatric effects of vitamin B12 deficiency belongs to Langdon in 1905. Vitamin B12 together with folate are essential for conversion of homocysteine to methionine and synthesis of adenosyl-methionine. S-adenosyl-methionine is responsible for methylation in the metabolism of neurotransmitters (5). There are various studies that showed associations of depression, dementia and schizophrenia with deficiencies of folate and vitamin B12. Some studies have focussed on folate rather than vitamin B12 and have suggested a stronger role for folate in depression. Independent from serum levels of folate and vitamin B12, augmention with these vitamins may be beneficial to patients who have predominantly cognitive symptoms, who are resistant to treatment, pregnantor use lithium (6).

Consequently, augmentation with omega-3 fatty acids, folate and vitamin B12 may have some clinical benefits in the treatment of some psychiatric disorders. However, mechanisms of their actions still need to be further elucidated.

References:

1. Bazan NG. Lipid signaling in neural plasticity, brain repair, and neuroprotection. Mol Neurobiol 2005; 32: 89–103
2. Yao JK, Leonard S, Reddy R. Altered glutathione redox state in schizophrenia. Dis Markers 2006; 22: 83–93
3. Frangou S, Lewis M, Wollard J, Simmons A. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder. J Psychopharmacol 2007; 21: 435-439
4. Berger GE, Wood SJ, Wellard RM, Proffitt TM, McConchie M, Amminger GP, Jackson GD, Velakoulis D, Pantelis C, McGorry PD. Ethyl-eicosapentaenoic acid in first-episode psychosis. A 1H-MRS study. Neuropsychopharmacology 2008; 33: 2467-2473
5. Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996; 54:382-390
6. Lindeman RD, Romero LJ, Koehler KM, Liang HC, LaRue A, Baumgartner RN, Garry PJ. Serum vitamin B12, C and folate concentrations in the New Mexico elder health survey: Correlations with cognitive and affective functions. J Am Coll Nutr 2000; 19: 68-76

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