Lack of association of SNPs from the FADS1-FADS2 gene cluster with major depression or suicidal behavior

Sublette, M. Elizabeth; Vaquero, Concepción; Baca‐García, Enrique; Pachano, Gabriela; Huang, Yung‐yu; Oquendo, María A.; Mann, J. John

doi:10.1097/ypg.0000000000000111

Cited by 9 publications

(5 citation statements)

References 78 publications

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“…This fatty acid signature would suggest that EPA+DHA deficits cannot be attributed to impaired microsomal desaturase and elongase activity. This is also supported by a recent genotyping study which did not observe an association between common single-nucleotide polymorphisms in FADS1 or FASD2 genes and depression or suicidality in MDD patients [127]. However, DNA methylation in the Elovl5 gene was found to be associated with depression and suicidality [128], and abnormalities in FADS1 and FADS2 mRNA expression have been observed in the postmortem prefrontal cortex of patients with mood disorders [129–131].…”

Section: Etiological Mechanismsmentioning

confidence: 54%

Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application

Messamore

Almeida

Jandacek

et al. 2017

Progress in Lipid Research

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A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders.

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Section: Etiological Mechanismsmentioning

confidence: 54%

Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application

Messamore

Almeida

Jandacek

et al. 2017

Progress in Lipid Research

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“…However, the link between FADS haplotype and the risk of developing neuropsychiatric disorders (schizophrenia or depression) is weak ( Fallin et al, 2004 ; Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium, 2011 ). A study conducted in patients with major depression found no association between FADS single nucleotide polymorphisms and major depression ( Sublette et al, 2016 ). Recently, a study suggested that genetic variation in the FADS gene influences the ω6/ω3 PUFAs ratio which appears to be associated with major depression ( Cribb et al, 2017 ).…”

Section: The Role Of ω3 Pufas In Depression and Anxiety Disordersmentioning

confidence: 99%

Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety

2018

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The central nervous system (CNS) has the highest concentration of lipids in the organism after adipose tissue. Among these lipids, the brain is particularly enriched with polyunsaturated fatty acids (PUFAs) represented by the omega-6 (ω6) and omega-3 (ω3) series. These PUFAs include arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively. PUFAs have received substantial attention as being relevant to many brain diseases, including anxiety and depression. This review addresses an important question in the area of nutritional neuroscience regarding the importance of ω3 PUFAs in the prevention and/or treatment of neuropsychiatric diseases, mainly depression and anxiety. In particular, it focuses on clinical and experimental data linking dietary intake of ω3 PUFAs and depression or anxiety. In particular, we will discuss recent experimental data highlighting how ω3 PUFAs can modulate neurobiological processes involved in the pathophysiology of anxiety and depression. Potential mechanisms involved in the neuroprotective and corrective activity of ω3 PUFAs in the brain are discussed, in particular the sensing activity of free fatty acid receptors and the activity of the PUFAs-derived endocannabinoid system and the hypothalamic–pituitary–adrenal axis.

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“…Previous research has explored the role of the FADS gene cluster in schizophrenia [ 33 ], response to omega-3 supplementation [ 39 ] and infant cognition [ 40 ]. Studies investigating the FADS genotype in MDD have been inconclusive, though sample sizes have been comparatively small [ 41 , 42 ]. On the one hand, this adds weight to the biological plausibility of causal inference, being involved in a rate-limiting step in the elongation of short-chain fatty acids to the long-chain derivatives important for brain health (such as EPA and DHA).…”

Section: Discussionmentioning

confidence: 99%

Omega-3 fatty acids and major depression: a Mendelian randomization study

Carnegie,

Borges,

Jones

et al. 2024

Transl Psychiatry

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Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so far been unsuccessful. Whether this association is causal remains unclear. We used two sample Mendelian randomization (MR) to investigate causality. Genetic variants associated with circulating omega-3 and omega-6 fatty acids in UK Biobank (UKBB, n = 115,078) were selected as exposures. The Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWAS) of MDD (n = 430,775; cases = 116,209; controls = 314,566) and recurrent depression (rMDD, n = 80,933; cases = 17,451; controls = 62,482), were used as outcomes. Multivariable MR (MVMR) models were used to account for biologically correlated lipids, such as high- and low-density cholesterol and triglycerides, and to explore the relative importance of longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) using data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866). Genetic colocalization analyses were used to explore the presence of a shared underlying causal variant between traits. Genetically predicted total omega-3 fatty acids reduced the odds of MDD (ORIVW 0.96 per standard deviation (SD, i.e. 0.22 mmol/l) (95% CIs 0.93–0.98, p = 0.003)). The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OREPA 0.92; 95% CI 0.88–0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. ‘Leave-one-out’ analyses highlighted the FADS gene cluster as a key driver of the effect. Colocalization analyses suggested a shared causal variant using the primary outcome sample, but genomic confounding could not be fully excluded. This study supports a role for omega-3 fatty acids, particularly EPA, in the aetiology of depression, although pleiotropic mechanisms cannot be ruled out. The findings support guidelines highlighting the importance of EPA dose and ratio for MDD and question whether targeted interventions may be superior to universal prevention trials, as modest effect sizes will limit statistical power.

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Lack of association of SNPs from the FADS1-FADS2 gene cluster with major depression or suicidal behavior

Cited by 9 publications

References 78 publications

Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application

Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical application

Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety

Omega-3 fatty acids and major depression: a Mendelian randomization study

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