Hypomethylation of MAOA׳s first exon region in depression: A replication study

Melas, Philippe A.; Forsell, Yvonne

doi:10.1016/j.psychres.2015.01.003

Cited by 38 publications

(41 citation statements)

References 7 publications

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“…While the present study consistently showed that hypermethylation of the MAOA ROI was associated with depression, two previous studies of males and females reported hypomethylation in this same region among depressed women (Melas et al 2013; Melas and Forsell 2015). The two previous studies included small samples with wide age ranges, a different measure of adversity, no measure of genotypes, and participants that may differ in comorbid disorders from the present sample.…”

Section: Discussionsupporting

confidence: 77%

“…The previous studies of methylation in this region among females also reported no association with a measure of adversity defined as parental death, divorce, financial problems, or other family problems (Melas et al 2013; Melas and Forsell 2015). …”

Section: Discussionmentioning

confidence: 77%

“…Methylation of the region flanking the MAOA first exon has been associated with MAO enzymatic activity in the brain (Shumay et al 2012), transcriptional downregulation in vitro, and with 5-HT levels in whole blood (Checknita et al 2015). In a recent study, higher methylation levels specific to the MAOA first exon were observed in women (mean 45.3%) compared to men (mean 13.7%) (Melas and Forsell 2015). Here, we report a similar level of methylation at MAOA exon 1 (mean 44.3%, SD 5.9) in women.…”

Section: Discussionmentioning

confidence: 93%

“…Stressful life events similarly associate with depression and anxiety (McCrory et al 2012). Hypermethylation of MAOA exon 1 was also observed among women relative to men, suggestive of X-chromosome inactivation given the gene’s location on the X-chromosome (Melas and Forsell 2015). It is not presently known whether PA and SA are associated with MAOA promoter methylation.…”

Section: Introductionmentioning

confidence: 98%

“…However, it is not known if hypermethylation is specifically associated with ASPD or with maltreatment that is common among men with ASPD (Hill and Nathan 2008), or substance use disorders that characterize almost all men with ASPD (Goldstein et al 2017), or anxiety disorders presented by approximately half of male offenders with ASPD (Hodgins et al 2010), or depression that is also elevated in this population (Lenzenweger et al 2007). Hypomethylation of this region was observed among women with depression (Melas et al 2013; Melas and Forsell 2015) and those with panic disorder relative to healthy women (Ziegler et al 2016). Stressful life events similarly associate with depression and anxiety (McCrory et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women

et al. 2018

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Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544–43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.Electronic supplementary materialThe online version of this article (10.1007/s00702-018-1875-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women

et al. 2018

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Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis

2017

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Type A monoamine oxidase (MAOA) catabolizes monoamine transmitters, serotonin, norepinephrine and dopamine, and plays a major role in the onset, progression and therapy of neuropsychiatric disorders. In depressive disorders, increase in MAOA expression and decrease in brain levels of serotonin and norepinephrine are proposed as the major pathogenic factors. The functional polymorphism of MAOA gene and genes in serotonin signal pathway are associated with depression. This review presents recent advance in studies on the role of MAOA in major depressive disorder and related emotional disorders. MAOA and serotonin regulate the prenatal development and postnatal maintenance of brain architecture and neurocircuit, as shown by MAOA-deficient humans and MAO knockout animal models. Impaired neurogenesis in the mature hippocampus has been proposed as "adult neurogenesis" hypothesis of depression. MAOA modulates the sensitivity to stress in the stages of brain development and maturation, and the interaction of gene-environmental factors in the early stage regulates the onset of depressive behaviors in adulthood. Vice versa environmental factors affect MAOA expression by epigenetic regulation. MAO inhibitors not only restore compromised neurotransmitters, but also protect neurons from cell death in depression through induction of anti-apoptotic Bcl-2 and prosurvival neurotrophic factors, especially brain-derived neurotrophic factor, the deficiency of which is detected in depression. This review discusses novel role of MAOA and serotonin in the pathogenesis and therapy of depressive disorders.

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Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons

2017

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Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death. MAO-A activity is regulated not only by genetic factor, but also by environmental factors, including stress, hormonal deregulation, and food factors. MAO-A activity fluctuates by genetic-environmental factors, modulates the neuronal response to the stimuli, and affects behavior and emotional activities. MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines. MAO-A knockdown suppressed the rasagiline-induced gene expression in SH-SY5Y cells, whereas MAO-B silencing enhanced the basal- and selegiline-induced gene expression in U118MG cells. MAO-A and B were shown to function as a mediator or repressor of gene expression, respectively. Further study on cellular mechanism underlying regulation of signal pathways by MAO-A and B may bring us a new insight on the role of MAOs in decision of neuronal fate and the development of novel therapeutic strategy may be expected for neuropsychiatric disorders.

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Hypomethylation of MAOA׳s first exon region in depression: A replication study

Cited by 38 publications

References 7 publications

Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women

Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women

Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis

Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons

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