Conceptualizing the role of estrogens and serotonin in the development and maintenance of bulimia nervosa

Abstract

Serotonergic dysregulation is thought to underlie much of the pathology in bulimia nervosa (BN). The purpose of this review is to expand the serotonergic model by incorporating specific and nonspecific contributions of estrogens to the development and maintenance of bulimic pathology in order to guide research from molecular genetics to novel therapeutics for BN. Special emphasis is given to the organizing theory of general brain arousal which allows for integration of specific and nonspecific effects of these systems on behavioral endpoints such as binge eating or purging as well as arousal states such as fear, novelty seeking, or sex. Regulation of the serotonergic system by estrogens is explored, and genetic, epigenetic, and environmental estrogen effects on bulimic pathology and risk factors are discussed. Genetic and neuroscientific research support this two-system conceptualization of BN with both contributions to the developmental and maintenance of the disorder. Implications of an estrogenic-serotonergic model of BN are discussed as well as guidelines and suggestions for future research and novel therapeutic targets.

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

“…We continue to believe that estrogen’s genetic effects during puberty are likely due to its traditional, genomic effects within the central nervous system. Extant data indicate that estrogen regulates gene transcription (i.e., estrogen turns genes on and off) within several neural systems (e.g., serotonin, dopamine, opioids; Becker, 2009; Craft, 2008; Culbert et al, 2009; Hildebrandt et al, 2010; Klump et al, 2003; Ostlund et al, 2003) that are disrupted in binge related phenotypes and eating disorders. Estrogen activation at puberty could lead to differential production of these important neurotransmitters, their receptors, or their signal transduction mechanisms.…”

Influences of Ovarian Hormones on Dysregulated Eating

“…As we have proposed previously (Klump, 2013; Klump et al, 2013a), it is likely that hormones influence dysregulated eating in all women via their regulatory effects on gene expression within the central nervous system. Ovarian hormones in general, and estrogen in particular, act as gene transcription factors to activate and de-activate genes within several neurotransmitter systems (e.g., serotonin, dopamine, opioids) that are believed to be important for binge eating and eating disorders characterized by binge eating (e.g., BN) (Becker, 1999; Craft, 2008; Hildebrandt, Alfano, Tricamo, & Pfaff, 2010; Ostlund, Keller, & Hurd, 2003). Ovarian hormone effects on dysregulated eating in all women therefore might result from the hormones’ effects on the production of these important neurotransmitters, their receptors, or their signal transduction mechanisms.…”

Genetic aspects of binge eating disorder Part 2. Molecular genetics and pharmacogenetic approaches

“…Существенное влияние нейроэндокринной систе-мы, в частности эстрогенов, на серотониновую нейроме-диацию делает перспективным изучение совместного генетического влияния этих систем на риск развития ВЕD [15]. Изучение других компонентов нейроэндо-кринной системы, например глюкокортикоидов, пока-зало связь полиморфизма rs6198 гена глюкокортикоид-ного рецептора с симптомами ВЕD, но не с анорексией и булимией, а полиморфизм rs56149945 (N363S) в этом же гене оказался связан с показателями индекса массы тела (body mass index, BMI) при ожирении вне зависимости от психопатологического варианта расстройства пищевого поведения [16].…”