Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder

McNamara, Robert K.; Hahn, Chang-Gyu; Jandacek, Ronald J.; Rider, Therese; Tso, Patrick; Stanford, Kevin E.; Richtand, Neil M.

doi:10.1016/j.biopsych.2006.08.026

Cited by 229 publications

(195 citation statements)

References 75 publications

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“…Decreased omega-3 fatty acid levels have been found in blood and postmortem brain cell membranes in several neuropsychiatric conditions (Schachter et al, 2005), in particular schizophrenia (Berger et al, 2006;Fenton et al, 2000;McNamara et al, 2007), bipolar affective disorders (Chiu et al, 2003;Hitzemann et al, 1984;Mahadik et al, 1996;Ranjekar et al, 2003), major depression (FrasureSmith et al, 2004;McNamara et al, 2006;Mischoulon and Fava, 2000;Peet et al, 1998), and attention deficit (hyperactivity) disorder (Burgess et al, 2000;Stevens et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Berger

Wood

Wellard

et al. 2008

Neuropsychopharmacol

107

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Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12 ¼ 6.1, p ¼ 0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20 ¼ 4.4, p ¼ 0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r ¼ À0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

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Section: Introductionmentioning

confidence: 99%

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Berger

Wood

Wellard

et al. 2008

Neuropsychopharmacol

107

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show abstract

“…Since aspirin, a cycloxygenase inhibitor, had no apparent effect on the desipramine-induced regeneration of NA axons (unpublished data, Nakamura), it seems unlikely that the cycloxygenase system would play a critical role in the desipramine-induced regeneration of NA axons. Many reports have shown lower levels of EPA and/or DHA being associated with clinical depression (Peet et al, 1998;De Vriese et al, 2003;Frasure-Smith et al, 2004;McNamara et al, 2007;Lin et al, 2010;Su et al, 2010). Animal studies demonstrated that administration of EPA and DHA had an antidepressant-like effect, reducing immobility in the forced swim test (Carlezon et al, 2005;Huang et al, 2008).…”

Section: Phospholipase A2mentioning

confidence: 99%

Antidepressants and Morphological Plasticity of Monoamine Neurons

Nakamura¹

2012

Effects of Antidepressants

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“…Although omega-3 PUFA levels in patients with major depressive disorder are consistently found to be reduced compared to healthy controls this defi ciency is not limited solely to EPA, with ALA and DHA also being diminished, and in a manner which is heterogeneous between different studies (reviewed in Ross, 2007). Indeed, although most studies have measured fatty acids levels in various blood compartments, one post mortem brain study reports that it is DHA levels which are reduced in the frontal cortex of patients with depression and bipolar disorder, although due to the very low abundance of EPA in brain the levels of this omega-3 PUFA were not assessed (McNamara et al 2007(McNamara et al , 2008. While a predominantly DHA involvement may suggest that omega-3 PUFA deficiency and antidepressant efficacy are uncorrelated, it cannot presently be ruled out that the brain may be much more sensitive to EPA defi ciency than to that of the other omega-3 PUFA species.…”

Section: Correction Of a Brain Omega-3 Pufa Defi Ciencymentioning

confidence: 99%

Article Commentary: The Emerging Role of Eicosapentaenoic Acid as an Important Psychoactive Natural Product: Some Answers but a Lot more Questions

Ross

2008

Lipid�Insights

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Omega-3 polyunsaturated fatty acids play important roles in both the structure and communication processes of cells. Dietary defi ciences of these fatty acids have been implicated in cardiac dysfunction, cancer and mood disorders. In the latter, clinical trials have strongly suggested that not all types of omega-3 PUFA are equally effi cacious. In particular eicosapentaenoic acid (EPA) appears to be the most useful in ameliorating the symptoms of major depressive disorder. The mechanism by which omega-3 PUFA have these effects, and why EPA is apparently more effective in this role than the much more abundant brain lipid docosahexaenoic acid, is unclear. The available data do suggest various biologically plausible mechanisms all of which are amenable to study using straightforward experimental approaches. To progress further, a better understanding of how EPA and other omega-3 PUFA effect neurophysiological and neurosignalling processes is required.

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Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder

Cited by 229 publications

References 75 publications

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Antidepressants and Morphological Plasticity of Monoamine Neurons

Article Commentary: The Emerging Role of Eicosapentaenoic Acid as an Important Psychoactive Natural Product: Some Answers but a Lot more Questions

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