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.

doi:10.1016/j.biopsych.2009.11.005

Cited by 159 publications

(115 citation statements)

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“…In addition, cPLA2 BanI polymorphism may be associated with somatic symptoms in MDD via the changes in EPA levels. PLA2 enzyme deacylates EPA from membrane phospholipids, thus an increased PLA2 enzyme activity in BanI GG genotypes may lead to depletion changes in EPA levels [21], which contributes to perception of somatic complaints in MDD [4]. On the other hand, although polymorphism of COX-2 rs4648308 genotypes have been associated with development of MDD, no association was found between COX-2 rs4648308 polymorphism and somtiac symptoms in MDD in this study.…”

Section: Discussioncontrasting

confidence: 61%

“…Moreover, genotypes of the key enzymes for phospholipids metabolism, such as Phospholipase A2 (PLA2) and cyclo-oxygenase-2 (COX-2), have been associated with major depressive disorder [19,20] and Interferon (IFN)-α induced depression [21]. The major subtype of PLA2 enzymes is the cytosolic A2 (cPLA2), and the gene for cPLA2 (PLA2G4A) has also been cloned and localized to chromosome 1q25 [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, MDD [19] and IFN-αinduced depression associated somatic symptoms [21] have been associated with GG genotype of BanI polymorphism of the cPLA2 gene, while development of major depression has been associated with COX-2 rs4648308 AG genotype [21].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, depression has also been associated with increased levels of pro-inflammatory markers, such as C-reactive protein (CRP) [31], and MDD associated somatic symptoms have also been associated with inflammation [4] and higher levels of proinflammatory cytokines [32]. The aim of the study is to investigate the effect of BanI polymorphism of cPLA2 gene and COX-2 rs4648308 polymorphism on somatic symptoms in MDD with a subset data from a larger study [21]. We hypothesized patients with Ban I GG genotype will have more somatic symptoms than those with BanI AA or AG genotypes.…”

Section: Introductionmentioning

confidence: 99%

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BanI polymorphism of cytosolic phospholipase A2 gene and somatic symptoms in medication-free acute depressed patients

Chang

Guu

Chen

et al. 2018

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Somatic symptoms are commonly seen in patients with major depressive disorder (MDD) and might be associated with inflammatory activation. Cytosolic phospholipase A2 (cPLA2) and cyclo-oxygenase-2 (COX-2) are the key enzymes in the metabolism of polyunsaturated fatty acids (PUFAs), which in turn may play an important role in inflammation and somatic symptoms in depression. This study investigated the effects of BanI polymorphism of cPLA2 gene and COX-2 rs4648308 genotypes on somatic symptoms and inflammatory marker in patients with MDD.Eighty-two patients with MDD were assessed for their psychopathology including 2 psychiatric and somatic symptoms, BanI polymorphism of cPLA2 and COX-2 rs4648308 genotypes and CRP levels. The results revealed that MDD patients with the cPLA2 BanI GG genotypes had higher somatic symptoms and higher levels of C-reactive protein (CRP), while no differences were found among the COX-2 rs4648308 genotypes. Inflammatory process, such as arachidonic acid cascade pathway, might help explain the effect of cPLA2 BanI polymorphism on the somatic symptoms, and may be a potential target for future investigation on treatment for MDD with somatic symptoms. However, the interpretation of the findings in this study is limited since we analyzed the data from a subset data from a larger study.

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Section: Discussioncontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BanI polymorphism of cytosolic phospholipase A2 gene and somatic symptoms in medication-free acute depressed patients

Chang

Guu

Chen

et al. 2018

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…Several quantitative assessments, rather than a categorical outcome of MDD, were selected because of increasing evidence that many genetic vulnerabilities may be associated with specific symptom clusters during IFN-a therapy (Lotrich et al, 2010;Lotrich et al, 2011;Su et al, 2010). Subjects were given the opportunity to either mail in questionnaire results or complete them on routine clinic days.…”

Section: Depression Assessmentmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Lotrich

Albusaysi

Ferrell

2012

Neuropsychopharmacol

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Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brainderived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Montgomery-Asberg Depression Rating Scale (MADRS) in 124 initially euthymic patients during treatment with interferon-alpha (IFN-a), assessing serum BDNF and rs6265. Using mixed-effect repeated measures, lower pretreatment BDNF was associated with higher depression symptoms during IFN-a treatment (F 144,17.2 ¼ 6.8; Po0.0001). However, although the Met allele was associated with lower BDNF levels (F 1,83.0 ¼ 5.0; P ¼ 0.03), it was only associated with increased MADRS scores (F 4,8.9 ¼ 20.3; Po0.001), and not the BDI-II or HADS. An exploratory comparison of individual BDI-II items indicated that the Met allele was associated with suicidal ideation, sadness, and worthlessness, but not neurovegetative symptoms. Conversely, the serotonin transporter promoter polymorphism (5-HTTLPR) short allele was associated with neurovegetative symptoms such as insomnia, poor appetite and fatigue, but not sadness, worthlessness, or suicidal ideation. IFN-a therapy further lowered BDNF serum levels (F 4,37.7 ¼ 5.0; P ¼ 0.003), but this decrease occurred regardless of depression development. The findings thus do not support the hypothesis that decreasing BDNF is the primary pathway by which IFN-a worsens depression. Nonetheless, the results support the hypothesis that BDNF levels influence resiliency against developing inflammatory cytokine-associated depression, and specifically to a subset of symptoms distinct from those influenced by 5-HTTLPR. Neuropsychopharmacology (2013) 38, 985-995;

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Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms

Tseng²,

Lin

et al. 2018

JAMA Netw Open

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107

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Key Points Question Is omega-3 polyunsaturated fatty acid treatment associated with an improvement in anxiety symptoms? Findings In this systematic review and meta-analysis of 19 clinical trials including 2240 participants from 11 countries, improvement in anxiety symptoms was associated with omega-3 polyunsaturated fatty acid treatment compared with controls in both placebo-controlled and non–placebo-controlled trials. The anxiolytic effects of omega-3 polyunsaturated fatty acids were also stronger in participants with clinical conditions than in subclinical populations. Meaning Omega-3 polyunsaturated fatty acid treatment for anxiety might be effective in clinical settings.

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

Cited by 159 publications

References 57 publications

BanI polymorphism of cytosolic phospholipase A2 gene and somatic symptoms in medication-free acute depressed patients

BanI polymorphism of cytosolic phospholipase A2 gene and somatic symptoms in medication-free acute depressed patients

Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms

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