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

Abstract

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.

The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

“…The enzyme product of MAOA breaks down the same monoamines increased at the synapse by SSRIs. Checknita et al 2018 did not find a significant effect of antidepressants on MAOA methylation in saliva, but it is unclear how well the DNA methylation in heterogeneous saliva cell samples correlates to cells of the CNS [64]. Domschke et al 2015 found a nominal association between 2 CpG sites within MAOA and response to escitalopram [65].…”

“…There are countless approaches to measure subjects' response to antidepressants, including scales of depression severity, functional level, suicidality, residual symptoms, and number of failed antidepressant trials [86]. Furthermore, the articles in our review often studied distinct populations that prevent generalizability of the results, such as combat-exposed male veterans [88] or females who had experienced physical and/or sexual abuse [64]. Methylation profiles of these samples may be affected by life experiences, comorbid anxiety disorders [65], or age [95].…”

“…Twenty-four articles met full inclusion criteria. The articles described the relationship between antidepressant administration and DNA methylation in the following genes: Brain-derived neurotrophic factor (BDNF) [49][50][51][52][53][54][55][57][58][59] (Table 1), monoamine oxidase A (MAOA) [64,65] (Table 2), 5-hydroxytryptamine (serotonin) transporter (SLC6A4) [67][68][69][70][71] (Table 3), norepinephrine transporter (SLC6A2) [72] (Table 3), 5-hydroxytryptamine transporters 1A and 1B (5HTR1A/1B) [77,78] (Table 4), interleukin-6 (IL6) [82], and interleukin-11 (IL11) [85] (Table 5). Two papers reported antidepressant effects on global DNA methylation [86,88] (Table 6).…”

“…Table 2 summarizes the included studies of the relationship between MAOA DNA methylation and antidepressant medications. Checknita et al 2018 examined methylation of the MAOA promoter in 114 young Swedish women with abuse histories compared to female controls [64]. Increased methylation of CpG-7/8 of MAOA occurred in women with active depression and lifetime use of psychotropic medication (stimulants, hypnotics, anxiolytics, antidepressants, and antipsychotics), but no significant differences in methylation occurred when lifetime antidepressant use alone was analyzed [64].…”

“…Checknita et al 2018 examined methylation of the MAOA promoter in 114 young Swedish women with abuse histories compared to female controls [64]. Increased methylation of CpG-7/8 of MAOA occurred in women with active depression and lifetime use of psychotropic medication (stimulants, hypnotics, anxiolytics, antidepressants, and antipsychotics), but no significant differences in methylation occurred when lifetime antidepressant use alone was analyzed [64]. Among women with current depression, higher methylation was associated with past or current use of any medication (stimulants, hypnotics, anxiolytics, antidepressants, or antipsychotics) at CpG 7/8.…”