The Impact of Environment on Mental Health – the Epigenetics of Bulimia
Bulimia Nervosa, a well-known eating disorder is commonly characterized by recurrent binge-eating, subsequent compensatory behaviors, and body image obsession. In addition to these common symptoms, some individuals with BN also suffer from other disorders such as mood fluctuations, anxiety, substance abuse, and personality problems. However, other individuals do not. Due to the variations in the presence of these secondary symptoms, it has been purposed that there may be multiple BN etiologies – and perhaps different biological and environmental factors contributing to the phenotypic variances in BN individuals.
Epigenetic mechanisms have been shown to be a link between environmental stimulus, such as a traumatic event, and mental illnesses. Additionally, alterations in the epigenetic status of specific genes have been correlated with certain disorders. For example, individuals with anorexia tend to have hypermethylation of the alpha-synuclein gene. Hypermethylation of the atrial natriuretic peptide gene promoter has been implicated in anxiety, depression, and stress.
Using these findings as a springboard, a recent study by Thaler et al. sought to investigate wither Bulimia may be influenced by, or associated with, alterations in DNA methylation profiling. The authors focus on the brain-derived neurotrophic factor (BDNF) gene because in the past, animal studies have shown that maltreatment corresponded with an increase in methylation. In human studies of post-traumatic stress disorder, individuals suffering from PTSD also displayed hypermethylation of the BDNF promoter. The group hypothesized that individuals with BN may display hypermethylation of BDNF, compared to normal-eater (NE) individuals.
Targeted bisulfite sequencing was used to survey the DNA methylation status of the BDNF gene in lymphocytes from whole blood. As they expected, they found that individuals with BN had increased DNA methylation at specific sites in the BDNF promoter compared to NE individuals. Although this finding itself is a thought-provoking conclusion, what they did next has some very interesting implications! They next split their BN group into several smaller groups – stratified by different traumatic events experienced by the individuals (such as abuse or maltreatment). Across the groups, there were a few sites that were consistently methylated in comparison to NE. However, different kinds of traumatic events among BN individuals were associated with methylation at different CpG sites along the BDNF promoter! When the group looked more closely at each site, they found that each one was a transcription factor binding site – implying that the significantly changed CpG sites that were found may be involved in separate regulatory pathways.
Traits such as personality and metal health are vastly complex and rely on the interaction of innumerable factors. The findings of this study may have broader implications than just within the field of BN research. DNA methylation is involved in more than merely turning a gene on or off – it may also serve as a way to regulate pathways by controlling availability of transcription factor binding sites in a context dependent manner, depending on the stimulus. This study provides insight into how multiple environmental factors work together to influence phenotypes through epigenetic regulation.
Thaler L, Gauvin L, Joober R, Groleau P, de Guzman R, Ambalavanan A, Israel M, Wilson S, & Steiger H (2014). Methylation of BDNF in women with bulimic eating syndromes: Associations with childhood abuse and borderline personality disorder. Progress in neuro-psychopharmacology & biological psychiatry, 54, 43-9 PMID: 24801751