MTHFR gene methylation is associated with perceived stress in healthy young adults

Jiménez, Karen M.; Pereira-Morales, Angela J.; Forero, Diego A.

doi:10.1097/ypg.0000000000000196

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…The epidemiological relationship between polysubstance use, defined as the consumption of more than one drug within a specified period of time, and several psychosocial factors (i.e., alcohol use, anxiety symptoms, and family functioning) in a Latin American sample was recently described by the group of Dr. Diego Forero at the Universidad Antonio Nariño , in Bogotá, Colombia (Pereira-Morales et al, 2017). In the same laboratory, methylenetetrahydrofolate reductase (MTHFR) methylation levels were found to be associated with perceived stress scores (Cohen’s Perceived Stress Scale), supporting vast evidence of epigenetic changes in stress and psychiatric disorders (Jiménez et al, 2018). In fact, the MTHFR C677T polymorphism has been associated with depression in the context of traumatic stress in early life (Lok et al, 2013), again pointing to genetic and epigenetic determinants of stress-induced negative affect.…”

Section: Latin American Non-clinical Studies and Translational Effortsmentioning

confidence: 82%

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

et al. 2018

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Drug addiction is a chronic neuropsychiatric disorder that escalates from an initial exposure to drugs of abuse, such as cocaine, cannabis, or heroin, to compulsive drug-seeking and intake, reduced ability to inhibit craving-induced behaviors, and repeated cycles of abstinence and relapse. It is well-known that chronic changes in the brain’s reward system play an important role in the neurobiology of addiction. Notably, environmental factors such as acute or chronic stress affect this system, and increase the risk for drug consumption and relapse. Indeed, the HPA axis, the autonomic nervous system, and the extended amygdala, among other brain stress systems, interact with the brain’s reward circuit involved in addictive behaviors. There has been a growing interest in studying the molecular, cellular, and behavioral mechanisms of stress and addiction in Latin-America over the last decade. Nonetheless, these contributions may not be as strongly acknowledged by the broad scientific audience as studies coming from developed countries. In this review, we compile for the first time a series of studies conducted by Latin American-based neuroscientists, who have devoted their careers to studying the interaction between stress and addiction, from a neurobiological and clinical perspective. Specific contributions about this interaction include the study of CRF receptors in the lateral septum, investigations on the neural mechanisms of cross-sensitization for psychostimulants and ethanol, the identification of the Wnt/β-catenin pathway as a critical neural substrate for stress and addiction, and the emergence of the cannabinoid system as a promising therapeutic target. We highlight animal and human studies, including for instance, reports coming from Latin American laboratories on single nucleotide polymorphisms in stress-related genes and potential biomarkers of vulnerability to addiction, that aim to bridge the knowledge from basic science to clinical research.

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Section: Latin American Non-clinical Studies and Translational Effortsmentioning

confidence: 82%

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

et al. 2018

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“…However, higher MTHFR DNAm was not associated with an increase in symptoms across ages 10, 13 and 15, and at the level of bivariate correlations, MTHFR DNAm at age 7 associated with lower depression symptoms at age 10, 13 and 15, combined. One other study has reported an association in a similar direction; an inverse association between MTHFR DNAm and depressive symptoms in a sample of young adults (mean age = 20.9 years; Jiménez et al, 2018). Taken together, these results imply an age-dependent association between MTHFR DNAm and depressive symptomatology, whereby higher DNAm during childhood is associated with increased early depressive symptoms (age 8) but lower depressive symptoms over time during late childhood and adolescence.…”

Section: Discussionmentioning

confidence: 66%

“…For example, a meta-analysis of 26 studies (4992 depression cases; 17,082 controls) suggested that the MTHFR C667T genotype can indeed contribute to increased depression risk (Wu et al, 2013). To date, only one published paper has examined MTHFR DNAm in association with depression symptoms, finding an inverse association with both perceived stress and depressive symptomatology (Jiménez, Pereira-Morales, & Forero, 2018). Research has yet to examine, in an integrative developmental model, whether DNAm in MTHFR associates with diet, serum cholesterol and depressive symptoms in children.…”

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confidence: 99%

Serum cholesterol, MTHFR methylation, and symptoms of depression in children.

Mesirow¹,

Roberts²,

Cecil³

et al. 2019

Developmental Psychology

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King's College LondonDepression is associated with dietary factors and epigenetics. Serum cholesterol, which is prone to dietary influences, has been linked to symptoms of depression. This relationship may be (in part) due to altered epigenetic regulation of Methylenetetrahydrofolate Reductase (MTHFR). MTHFR codes for the MTHFR enzyme, which has diverse metabolic functions, and has recently been linked individually with diet, serum cholesterol levels and depressive symptoms. In 514 mother-child pairs, we examined prospective relationships between maternal (pregnancy) and child (7 years) serum cholesterol, MTHFR DNA methylation (DNAm; birth, 7 years), and development of depression symptoms from 8 -15 years. After adjusting for potential confounding, we had three main findings. First, higher prenatal cholesterol associated (at a small effect size) with higher MTHFR DNAm at birth. Second, there was small effect size continuity for MTHFR DNAm between birth and age 7. Third, higher age 7 MTHFR DNAm associated with higher initial symptoms of depression symptoms at age 8, again at a small effect size. Overall, our findings provide preliminary evidence for a relationship between prenatal cholesterol, MTHFR DNAm, and symptoms of depression in children.

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“…Some implied a direct impact on the regulation of the monoamines and neurotransmitters (COMT and MAO) and other indicated a direct involvement in the response to stress (e.g. NR3C1, 24) and methylenetetrahydrofolate reductase (MTHFR) [25] ( may lead to higher DA levels in the brain cortex, reduced pain threshold and enhanced vulnerability to stress, what could align with the upper limit blood DA levels found in the patient (Table 1). Additional missense variants in heterozygosis: Ala222Val of the MTHFR leads to reduced processing of folic acid and Val16Ala of the superoxide dismutase (SOD) gene translates into oxidative stress alterations.…”

Section: Biochemical and Genetic Analysesmentioning

confidence: 65%

Stress-Related Chronic Fatigue Syndrome: A Case Report with Positive Response to Alpha-Methyl-P-Tyrosine (AMPT) Treatment

Ljungström,

Oltra,

Pardo

2024

Preprint

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Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

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MTHFR gene methylation is associated with perceived stress in healthy young adults

Abstract: To our knowledge, this is the first study that reports an association between perceived stress and MTHFR methylation levels. This report adds evidence to the emerging role of epigenetic changes in endophenotypes related to affective disorders.

Cited by 8 publications

References 54 publications

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

Serum cholesterol, MTHFR methylation, and symptoms of depression in children.

Stress-Related Chronic Fatigue Syndrome: A Case Report with Positive Response to Alpha-Methyl-P-Tyrosine (AMPT) Treatment

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