Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-α-Induced Depression by Regulating Polyunsaturated Fatty Acids Levels

Kuan Pin Su, Shih Yi Huang, Cheng Yuan Peng, Hsueh Chou Lai, Chieh Liang Huang, Yi Chih Chen, Katherine J. Aitchison, Carmine M. Pariante

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Abstract

Background: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Methods: Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-α treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent "replication" sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined. Results: Twenty-eight percent of participants developed INF-α-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-α-induced depression (odds ratio = 3.1 and 3.5, respectively). The "at risk" PLA2 genotype was associated with lower EPA levels, and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN-α treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-α-induced depression and in the replication sample of patients with major depression. Conclusions: Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-α-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

Original languageEnglish
Pages (from-to)550-557
Number of pages8
JournalBiological Psychiatry
Volume67
Issue number6
DOIs
Publication statusPublished - Mar 15 2010

Fingerprint

Phospholipases A2
Cyclooxygenase 2
Unsaturated Fatty Acids
Interferons
Depression
Genes
Eicosapentaenoic Acid
Docosahexaenoic Acids
Genotype
Cytokines
Illness Behavior
Chronic Hepatitis C
Virus Diseases
Arachidonic Acid
Single Nucleotide Polymorphism
Therapeutics
Erythrocytes
Odds Ratio

Keywords

  • Cyclooxygenase 2 (COX-2)
  • cytokine
  • depression
  • immune
  • inflammation
  • interleukin (IL)-6
  • phospholipase A2 (PLA2)
  • polyunsaturated fatty acids (PUFAs)
  • prostaglandins
  • psychoneuroimmunology

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-α-Induced Depression by Regulating Polyunsaturated Fatty Acids Levels. / Su, Kuan Pin; Huang, Shih Yi; Peng, Cheng Yuan; Lai, Hsueh Chou; Huang, Chieh Liang; Chen, Yi Chih; Aitchison, Katherine J.; Pariante, Carmine M.

In: Biological Psychiatry, Vol. 67, No. 6, 15.03.2010, p. 550-557.

Research output: Contribution to journalArticle

Su, Kuan Pin ; Huang, Shih Yi ; Peng, Cheng Yuan ; Lai, Hsueh Chou ; Huang, Chieh Liang ; Chen, Yi Chih ; Aitchison, Katherine J. ; Pariante, Carmine M. / Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-α-Induced Depression by Regulating Polyunsaturated Fatty Acids Levels. In: Biological Psychiatry. 2010 ; Vol. 67, No. 6. pp. 550-557.
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abstract = "Background: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Methods: Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-α treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent {"}replication{"} sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined. Results: Twenty-eight percent of participants developed INF-α-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-α-induced depression (odds ratio = 3.1 and 3.5, respectively). The {"}at risk{"} PLA2 genotype was associated with lower EPA levels, and the {"}at risk{"} COX2 genotype was associated with lower DHA levels, during IFN-α treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-α-induced depression and in the replication sample of patients with major depression. Conclusions: Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-α-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.",
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T1 - Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-α-Induced Depression by Regulating Polyunsaturated Fatty Acids Levels

AU - Su, Kuan Pin

AU - Huang, Shih Yi

AU - Peng, Cheng Yuan

AU - Lai, Hsueh Chou

AU - Huang, Chieh Liang

AU - Chen, Yi Chih

AU - Aitchison, Katherine J.

AU - Pariante, Carmine M.

PY - 2010/3/15

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N2 - Background: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Methods: Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-α treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent "replication" sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined. Results: Twenty-eight percent of participants developed INF-α-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-α-induced depression (odds ratio = 3.1 and 3.5, respectively). The "at risk" PLA2 genotype was associated with lower EPA levels, and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN-α treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-α-induced depression and in the replication sample of patients with major depression. Conclusions: Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-α-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

AB - Background: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Methods: Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-α treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent "replication" sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined. Results: Twenty-eight percent of participants developed INF-α-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-α-induced depression (odds ratio = 3.1 and 3.5, respectively). The "at risk" PLA2 genotype was associated with lower EPA levels, and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN-α treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-α-induced depression and in the replication sample of patients with major depression. Conclusions: Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-α-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

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KW - inflammation

KW - interleukin (IL)-6

KW - phospholipase A2 (PLA2)

KW - polyunsaturated fatty acids (PUFAs)

KW - prostaglandins

KW - psychoneuroimmunology

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