Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients

Kuan Pin Su, Hui Ting Yang, Jane Pei Chen Chang, Yin Hua Shih, Ta Wei Guu, Satyanarayanan Senthil Kumaran, Piotr Gałecki, Anna Walczewska, Carmine M. Pariante

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been proven critical in the development and management of major depressive disorder (MDD) by a number of epidemiological, clinical and preclinical studies, but the molecular mechanisms underlying this therapeutic action are yet to be understood. Although eicosapentaenoic acid (EPA) seems to be the active component of omega-3 PUFAs' antidepressant effects, the biological research about the difference of specific genetic regulations between EPA and docosahexaenoic acid (DHA), the two main components of omega-3 PUFAs, is still lacking in human subjects. Methods We conducted a 12-week randomized-controlled trial comparing the effects of EPA and DHA on gene expressions of phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX2), serotonin transporter (5HTT), and Tryptophan hydroxylase 2 (TPH-2) in 27 MDD patients. In addition, the erythrocyte PUFA compositions and the candidate gene expressions were also compared between these 27 MDD patients and 22 healthy controls. Results EPA was associated with a significant decrease in HAM-D scores (CI: − 13 to − 21, p < 0.001) and significant increases in erythrocyte levels of EPA (CI: + 1.0% to + 2.9%, p = 0.001) and DHA (CI: + 2.9% to + 5.6%, p = 0.007). DHA treatment was associated with a significant decrease in HAM-D scores (CI: − 6 to − 14, p < 0.001) and a significant increase in DHA levels (CI: + 0.2% to + 2.3%, p = 0.047), but not of EPA levels. The cPLA2 gene expression levels were significantly increased in patients received EPA (1.9 folds, p = 0.038), but not DHA (1.08 folds, p = 0.92). There was a tendency for both EPA and DHA groups to decrease COX-2 gene expressions. The gene expressions of COX-2, cPLA2, TPH-2 and 5-HTT did not differ between MDD cases and healthy controls. Conclusions EPA differentiates from DHA in clinical antidepressant efficacy and in upregulating cPLA2 gene regulations, which supports the clinical observation showing the superiority of EPA's antidepressant effects. Trial registration: ClinicalTrials.gov identifier: NCT02615405

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume80
DOIs
Publication statusPublished - Jan 3 2018
Externally publishedYes

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Eicosapentaenoic Acid
Docosahexaenoic Acids
Phospholipases A2
Gene Expression
Major Depressive Disorder
Unsaturated Fatty Acids
Omega-3 Fatty Acids
Antidepressive Agents
Tryptophan Hydroxylase
Erythrocytes
Serotonin Plasma Membrane Transport Proteins
Cyclooxygenase 2
Randomized Controlled Trials
Observation

Keywords

  • Docosahexaenoic acid (DHA)
  • Eicosapentaenoic acid (EPA)
  • Gene expressions
  • Major depressive disorder (MDD)
  • Omega-3 polyunsaturated fatty acids (n-3 PUFAs)
  • Phospholipase A2 (PLA2)

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this

Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients. / Su, Kuan Pin; Yang, Hui Ting; Chang, Jane Pei Chen; Shih, Yin Hua; Guu, Ta Wei; Kumaran, Satyanarayanan Senthil; Gałecki, Piotr; Walczewska, Anna; Pariante, Carmine M.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 80, 03.01.2018, p. 227-233.

Research output: Contribution to journalArticle

Su, Kuan Pin ; Yang, Hui Ting ; Chang, Jane Pei Chen ; Shih, Yin Hua ; Guu, Ta Wei ; Kumaran, Satyanarayanan Senthil ; Gałecki, Piotr ; Walczewska, Anna ; Pariante, Carmine M. / Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018 ; Vol. 80. pp. 227-233.
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title = "Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients",
abstract = "Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been proven critical in the development and management of major depressive disorder (MDD) by a number of epidemiological, clinical and preclinical studies, but the molecular mechanisms underlying this therapeutic action are yet to be understood. Although eicosapentaenoic acid (EPA) seems to be the active component of omega-3 PUFAs' antidepressant effects, the biological research about the difference of specific genetic regulations between EPA and docosahexaenoic acid (DHA), the two main components of omega-3 PUFAs, is still lacking in human subjects. Methods We conducted a 12-week randomized-controlled trial comparing the effects of EPA and DHA on gene expressions of phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX2), serotonin transporter (5HTT), and Tryptophan hydroxylase 2 (TPH-2) in 27 MDD patients. In addition, the erythrocyte PUFA compositions and the candidate gene expressions were also compared between these 27 MDD patients and 22 healthy controls. Results EPA was associated with a significant decrease in HAM-D scores (CI: − 13 to − 21, p < 0.001) and significant increases in erythrocyte levels of EPA (CI: + 1.0{\%} to + 2.9{\%}, p = 0.001) and DHA (CI: + 2.9{\%} to + 5.6{\%}, p = 0.007). DHA treatment was associated with a significant decrease in HAM-D scores (CI: − 6 to − 14, p < 0.001) and a significant increase in DHA levels (CI: + 0.2{\%} to + 2.3{\%}, p = 0.047), but not of EPA levels. The cPLA2 gene expression levels were significantly increased in patients received EPA (1.9 folds, p = 0.038), but not DHA (1.08 folds, p = 0.92). There was a tendency for both EPA and DHA groups to decrease COX-2 gene expressions. The gene expressions of COX-2, cPLA2, TPH-2 and 5-HTT did not differ between MDD cases and healthy controls. Conclusions EPA differentiates from DHA in clinical antidepressant efficacy and in upregulating cPLA2 gene regulations, which supports the clinical observation showing the superiority of EPA's antidepressant effects. Trial registration: ClinicalTrials.gov identifier: NCT02615405",
keywords = "Docosahexaenoic acid (DHA), Eicosapentaenoic acid (EPA), Gene expressions, Major depressive disorder (MDD), Omega-3 polyunsaturated fatty acids (n-3 PUFAs), Phospholipase A2 (PLA2)",
author = "Su, {Kuan Pin} and Yang, {Hui Ting} and Chang, {Jane Pei Chen} and Shih, {Yin Hua} and Guu, {Ta Wei} and Kumaran, {Satyanarayanan Senthil} and Piotr Gałecki and Anna Walczewska and Pariante, {Carmine M.}",
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T1 - Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients

AU - Su, Kuan Pin

AU - Yang, Hui Ting

AU - Chang, Jane Pei Chen

AU - Shih, Yin Hua

AU - Guu, Ta Wei

AU - Kumaran, Satyanarayanan Senthil

AU - Gałecki, Piotr

AU - Walczewska, Anna

AU - Pariante, Carmine M.

PY - 2018/1/3

Y1 - 2018/1/3

N2 - Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been proven critical in the development and management of major depressive disorder (MDD) by a number of epidemiological, clinical and preclinical studies, but the molecular mechanisms underlying this therapeutic action are yet to be understood. Although eicosapentaenoic acid (EPA) seems to be the active component of omega-3 PUFAs' antidepressant effects, the biological research about the difference of specific genetic regulations between EPA and docosahexaenoic acid (DHA), the two main components of omega-3 PUFAs, is still lacking in human subjects. Methods We conducted a 12-week randomized-controlled trial comparing the effects of EPA and DHA on gene expressions of phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX2), serotonin transporter (5HTT), and Tryptophan hydroxylase 2 (TPH-2) in 27 MDD patients. In addition, the erythrocyte PUFA compositions and the candidate gene expressions were also compared between these 27 MDD patients and 22 healthy controls. Results EPA was associated with a significant decrease in HAM-D scores (CI: − 13 to − 21, p < 0.001) and significant increases in erythrocyte levels of EPA (CI: + 1.0% to + 2.9%, p = 0.001) and DHA (CI: + 2.9% to + 5.6%, p = 0.007). DHA treatment was associated with a significant decrease in HAM-D scores (CI: − 6 to − 14, p < 0.001) and a significant increase in DHA levels (CI: + 0.2% to + 2.3%, p = 0.047), but not of EPA levels. The cPLA2 gene expression levels were significantly increased in patients received EPA (1.9 folds, p = 0.038), but not DHA (1.08 folds, p = 0.92). There was a tendency for both EPA and DHA groups to decrease COX-2 gene expressions. The gene expressions of COX-2, cPLA2, TPH-2 and 5-HTT did not differ between MDD cases and healthy controls. Conclusions EPA differentiates from DHA in clinical antidepressant efficacy and in upregulating cPLA2 gene regulations, which supports the clinical observation showing the superiority of EPA's antidepressant effects. Trial registration: ClinicalTrials.gov identifier: NCT02615405

AB - Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been proven critical in the development and management of major depressive disorder (MDD) by a number of epidemiological, clinical and preclinical studies, but the molecular mechanisms underlying this therapeutic action are yet to be understood. Although eicosapentaenoic acid (EPA) seems to be the active component of omega-3 PUFAs' antidepressant effects, the biological research about the difference of specific genetic regulations between EPA and docosahexaenoic acid (DHA), the two main components of omega-3 PUFAs, is still lacking in human subjects. Methods We conducted a 12-week randomized-controlled trial comparing the effects of EPA and DHA on gene expressions of phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX2), serotonin transporter (5HTT), and Tryptophan hydroxylase 2 (TPH-2) in 27 MDD patients. In addition, the erythrocyte PUFA compositions and the candidate gene expressions were also compared between these 27 MDD patients and 22 healthy controls. Results EPA was associated with a significant decrease in HAM-D scores (CI: − 13 to − 21, p < 0.001) and significant increases in erythrocyte levels of EPA (CI: + 1.0% to + 2.9%, p = 0.001) and DHA (CI: + 2.9% to + 5.6%, p = 0.007). DHA treatment was associated with a significant decrease in HAM-D scores (CI: − 6 to − 14, p < 0.001) and a significant increase in DHA levels (CI: + 0.2% to + 2.3%, p = 0.047), but not of EPA levels. The cPLA2 gene expression levels were significantly increased in patients received EPA (1.9 folds, p = 0.038), but not DHA (1.08 folds, p = 0.92). There was a tendency for both EPA and DHA groups to decrease COX-2 gene expressions. The gene expressions of COX-2, cPLA2, TPH-2 and 5-HTT did not differ between MDD cases and healthy controls. Conclusions EPA differentiates from DHA in clinical antidepressant efficacy and in upregulating cPLA2 gene regulations, which supports the clinical observation showing the superiority of EPA's antidepressant effects. Trial registration: ClinicalTrials.gov identifier: NCT02615405

KW - Docosahexaenoic acid (DHA)

KW - Eicosapentaenoic acid (EPA)

KW - Gene expressions

KW - Major depressive disorder (MDD)

KW - Omega-3 polyunsaturated fatty acids (n-3 PUFAs)

KW - Phospholipase A2 (PLA2)

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