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MTHFR C677T Major Depressive Disorder

Kevin Cho, Zubair M Amin, Jie An, Kerry Anne Rambaran, Tyler B Johnson, Saeed K Alzghari
Major depressive disorder (MDD) is a disorder that carries significant psychosocial and economic implications. Research efforts have focused on identifying biomarkers that can aid in the prediction, diagnosis, and efficacious treatment of MDD. Most of this focus has been placed on a polymorphism of the methylenetetrahydrofolate reductase ( MTHFR ) gene, C677T. MTHFR C677T is screened during MDD diagnosis in many protocols. However, MTHFR C667T poses conflicting data in various ethnic groups and geographic populations calling into question its utility...
October 1, 2017: Curēus
Mohamed Amine Sayadi, Ons Achour, Asma Ezzaher, Ilham Hellara, Asma Omezzine, Wahiba Douki, Ali Bousslama, Lotfi Gaha, Mohamed Fadhel Najjar
BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis...
2016: Annals of General Psychiatry
Arnold W Mech, Andrew Farah
OBJECTIVE: This study was designed to evaluate the efficacy and safety of reduced B vitamins as monotherapy in adults with major depressive disorder (MDD) who were also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with depression and further test the hypothesis that reduced (metabolized) B vitamins will lower homocysteine in a majority of clinically responding patients. METHODS: 330 adult patients with MDD (DSM-5) and positive for either MTHFR C677T or A1298C polymorphism were enrolled in a trial conducted between August 1, 2014, and April 3, 2015...
May 2016: Journal of Clinical Psychiatry
N Eszlari, D Kovacs, P Petschner, D Pap, X Gonda, R Elliott, I M Anderson, J F W Deakin, G Bagdy, G Juhasz
Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309)...
March 1, 2016: Translational Psychiatry
Maria Gabriela Nielsen, Chiara Congiu, Marco Bortolomasi, Cristian Bonvicini, Stefano Bignotti, Maria Abate, Elena Milanesi, Andreas Conca, Nadia Cattane, Elisabetta Tessari, Massimo Gennarelli, Alessandra Minelli
BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) genetic variations have been widely studied in major depressive disorder (MDD) and antidepressants outcome. An interaction with catechol-O-methyltransferase (COMT) has also been proved affecting depression. The aim of this study was to clarify the role of the most commonly studied single nucleotide polymorphisms (SNPs) of MTHFR gene in MDD and in treatment response mechanisms, along with the impact of the interaction with COMT. METHODS: A total of 613 MDD patients, of whom 389 were classified as having treatment resistant depression (TRD), and 463 controls were enrolled...
September 1, 2015: Journal of Affective Disorders
A Lok, R J T Mocking, J Assies, M W Koeter, C L Bockting, G J de Vries, I Visser, E M Derks, M Kayser, A H Schene
BACKGROUND: An important biological factor suggested in the pathophysiology of (recurrent) Major Depressive Disorder (MDD) concerns a polymorphism in a gene encoding for the MTHFR-enzyme of the one-carbon (1-C)-metabolism. Integratively investigating key 1-C-components (folate, homocysteine, vitamin B6 and B12), including the possible effects of antidepressant medication and depressive state, could provide more insight in the possible association between the MTHFR-polymorphism and recurrent MDD...
September 2014: Journal of Affective Disorders
Xinhua Shen, Yanfeng Wu, Tiefeng Guan, Xiaoquan Wang, Mincai Qian, Min Lin, Zhongxia Shen, Jushui Sun, Hua Zhong, Jianhong Yang, Liang Li, Yonggui Yuan
BACKGROUND: In several previous biochemical and genetic studies, the Val158Met polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been suggested to be involved in the pathogenesis as well as the treatment response of major depressive disorder (MDD), but the results have been inconsistent. In this study, we investigate the association of COMT/MTHFR and their interactions with MDD and antidepressant response in Chinese Han population...
June 2014: Journal of Affective Disorders
Xiaoquan Wang, Zusen Wang, Yanfeng Wu, Yonggui Yuan, Zhenghua Hou, Gang Hou
AIMS: Increasing evidence suggests that the catechol-O-methyltransferase (COMT) gene might be associated with cognition in patients with mental disorders and healthy people. The metabolic pathways of COMT and methylenetetrahydrofolate reductase (MTHFR) are closely interconnected. In this study, we aimed to examine whether the COMT-MTHFR genotype interacted with cognitive function in late-onset depression (LOD) patients and COMT Val/Val homozygous individuals who also carried the MTHFR T allele and had poor neuropsychological test performance...
May 2014: Psychiatry and Clinical Neurosciences
Chad A Bousman, Maria Potiriadis, Ian P Everall, Jane M Gunn
Methylenetetrahydrofolate reductase (MTHFR) genetic variation has been associated with the diagnosis of major depressive disorder (MDD) but no study to date has examined the effect MTHFR variation has on MDD prognosis. We sought to examine the prospective effects of two common MTHFR variants (C677T and A1298C) as well as seven haplotype-tagging single nucleotide polymorphisms (htSNPs) on MDD prognosis over a 5-year (60-month) period. Participants were 147 depressed primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study...
January 2014: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
A Lok, C L H Bockting, M W J Koeter, H Snieder, J Assies, R J T Mocking, C H Vinkers, R S Kahn, M P Boks, A H Schene
Childhood trauma is associated with the onset and recurrence of major depressive disorder (MDD). The thermolabile T variant of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) is associated with a limited (oxidative) stress defense. Therefore, C677T MTHFR could be a potential predictor for depressive symptomatology and MDD recurrence in the context of traumatic stress during early life. We investigated the interaction between the C677T MTHFR variant and exposure to traumatic childhood events (TCEs) on MDD recurrence during a 5...
2013: Translational Psychiatry
Andrea Evinova, Eva Babusikova, Stanislav Straka, Igor Ondrejka, Jan Lehotsky
Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder...
December 2012: General Physiology and Biophysics
Elizabeth E Trimmer
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydofolate (CH2-H4folate) to 5-methyltetrahydrofolate (CH3-H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide (FAD), which accepts reducing equivalents from NAD(P)H and transfers them to CH2-H4folate. The reaction provides the sole source of CH3-H4folate, which is utilized by methionine synthase in the synthesis of methionine from homocysteine. MTHFR plays a key role in folate metabolism and in the homeostasis of homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia...
2013: Current Pharmaceutical Design
David Mischoulon, Stefania Lamon-Fava, Jacob Selhub, Judith Katz, George I Papakostas, Dan V Iosifescu, Albert S Yeung, Christina M Dording, Amy H Farabaugh, Alisabet J Clain, Lee Baer, Jonathan E Alpert, Andrew A Nierenberg, Maurizio Fava
OBJECTIVE: To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. METHODS: We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20-60 mg/day...
June 2012: CNS Spectrums
Asma Ezzaher, Dhouha Haj Mouhamed, Anwar Mechri, Asma Omezzine, Fadoua Neffati, Wahiba Douki, Ali Bouslama, Lotfi Gaha, Mohamed Fadhel Najjar
AIMS: The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism...
December 2011: Psychiatry and Clinical Neurosciences
Odette L J Peerbooms, Jim van Os, Marjan Drukker, Gunter Kenis, Loes Hoogveld, Marc de Hert, Philippe Delespaul, Ruud van Winkel, Bart P F Rutten
Past analyses examining the relationship between genetic variation in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders have provided mixed and largely inconclusive findings. MTHFR is involved in the one-carbon metabolic pathway which is essential for DNA biosynthesis and the epigenetic process of DNA methylation. We conducted a meta-analysis of all published case-control studies investigating associations between two common MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T (sample size 29,502) and A1298C (sample size 7934), and the major psychiatric disorders (i) schizophrenia (SZ), (ii) bipolar disorder (BPD), and (iii) unipolar depressive disorder (UDD)...
November 2011: Brain, Behavior, and Immunity
Edmund D Hong, Warren D Taylor, Douglas R McQuoid, Guy G Potter, Martha E Payne, Allison Ashley-Koch, David C Steffens
OBJECTIVE: The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been linked to unipolar major depressive disorder (MDD) and magnetic resonance imaging (MRI) hyperintensities. The authors examined the relationship between the MTHFR C677T polymorphism (C677T) and a) geriatric depression, b) MRI hyperintense lesion volume, and c) neurocognitive test performance. DESIGN: Cross-sectional. SETTING: Duke University Medical Center. PARTICIPANTS: Depressed (N = 178) and comparison (N = 85) elderly subjects...
October 2009: American Journal of Geriatric Psychiatry
Chih-Chuan Pan, Douglas R McQuoid, Warren D Taylor, Martha E Payne, Allison Ashley-Koch, David C Steffens
OBJECTIVE: Catechol-O-Methyltransferase (COMT) and Methylenetetrahydrofolate reductase (MTHFR) had been reported to relate to depression but with inconsistent results. The basal ganglia are also important in the pathophysiology of affective disorder via connections with limbic system and prefrontal cortex. The authors examined the relationship between an interaction of COMT/MTHFR polymorphisms and volumes of putamen in depressed and nondepressed elders. METHODS: Participants included 170 depressed and 83 nondepressed subjects aged 60 years or older...
August 2009: International Journal of Geriatric Psychiatry
D Gaysina, S Cohen, N Craddock, A Farmer, F Hoda, A Korszun, M J Owen, I W Craig, P McGuffin
Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta-analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations...
September 5, 2008: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Cheng-Sheng Chen, Jer-Chia Tsai, Hin-Yeung Tsang, Yu-Ting Kuo, Hsiu-Fen Lin, I-Chan Chiang, D P Devanand
OBJECTIVE: Epidemiological studies suggest that elevated plasma homocysteine is associated with an increased risk of depression and cerebrovascular disease. There are no published reports of homocysteine levels and methylenetetrahydrofolate reductase (MTHFR) C677T genotype in clinical samples of patients with late-onset major depressive disorder (MDD). The purpose of this study was to examine the association of homocysteine levels or MTHFR C677T genotype and late-onset MDD and assess whether this may be affected by brain magnetic resonance imaging (MRI) hyperintensities...
October 2005: American Journal of Geriatric Psychiatry
Alec Coppen, Christina Bolander-Gouaille
We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism...
January 2005: Journal of Psychopharmacology
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