Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that is involved in just about everything. It helps ensure proper cell growth, maturation and migration during development. Serotonin is also important in regulating emotions, cognitive functions, appetite, pain, circadian rhythms, and our endocrine system in adulthood. It is hardly a surprise then, that the serotonergic system seems to be important in bulimia nervosa (BN).
I’ve written previously about serotonin in restricting-type anorexia nervosa, so for this post I’m going to be shifting focus and talk about bulimia and binge-purge type anorexia nervosa (AN-BP).
The information in this post isn’t coming from a review paper. Instead, I’m going to be summarizing and explaining information from a chapter in a book titled Behavioural Neurobiology of Eating Disorders. In the chapter on serotonin and bulimia, Howard Steiger and colleagues propose a model for serotonin action in bulimia nervosa which takes into account “diverse hereditary and environmental influences… and helps account for heterogeneous traits seen in the bulimic population“.
Individuals whose eating disorders are characterized by the presence of binge-eating and purging display a range of temperamental traits, but the intensity and the number of traits vary from person to person. In other words, no two BN or binge-purge AN patients are the same, and many can be really different. Of course, this makes it difficult to understand (and to study) the factors that lead individuals to engage in binge-eating and purging behaviours.
This means that you’ll likely see lots of contradictory studies or mutually exclusive theories about serotonin function in bulimia – and eating disorders in general. This is normal in any young field – and neurobiology and genetics of EDs is a very young field. It may be that some of what we (and by “we”, I mean scientists) think about EDs is wrong, but a more likely alternative (if contradictory studies are methodologically sound) is that a lot of things are right (or true), but perhaps for a specific subset of this heterogeneous population (for example, someone with comorbid borderline personality disorder might have very different BN etiology compared to someone with a long history of AN and no psychiatric comorbidities.) My point with this diversion is mainly to remind readers that science is a process and not a collection of facts and some bits of knowledge have more empirical support than others.
Okay, anyway, let’s get back to the topic of serotonin and bulimia.
According to several studies, individuals with bulimic symptoms can be – very roughly – categorized into three groups: about a third are highly emotional, impulsive, and dis-inhibited (“dysregulated”); another third is detail-oriented, compulsive and has difficulty switching cognitive thinking patterns (“over-regulated”); and the last third is “quite free of observable psychopathology”.
These differences likely play a role in the etiology (causes), clinical presentation and course of the disorder. They may also – at least in part – explain the variability in treatment outcomes (why does CBT work for some, but not for others?) My hunch is that the “over-regulated” group is probably more likely than the “dysregulated” group to have suffered from anorexia nervosa prior to BN.
Some things we know about the role of serotonin are well-established, whereas others are more controversial (which often means there are contradictory studies in the literature).
Serotonin appears to be important in mediating harm assessment and harm avoidance. (In psychology, the term “harm avoidance” is much more complex than the literal definition of avoiding harm, it includes traits such as “excessive worrying; pessimism; shyness; and being fearful, doubtful, and easily fatigued”.) Decreasing serotonin neurotransmission is correlated with an inability to inhibit responses and “adopt cautious waiting attitudes.”
Less well-established is the association of increased serotonin neurotransmission with behavioural inhibition, compulsiveness, inflexibility and enhanced vigilance. The inconsistencies may be due to faulty methodology in some studies, or perhaps due to the fact that maybe serotonin is less important in mediating these traits.
Low levels of serotonin are associated with a propensity toward “impulsive aggression, suicidality, and self-injuriousness”.
The next obvious question is: what regulates the level of serotonin in the brain?
As it turns out (and I apologize for the repetition for those who have read my previous post on serotonin), food is a crucial source of serotonin. Okay, not exactly serotonin but a precursor to serotonin – the molecule that is required to make serotonin – tryptophan. Tryptophan is an essential amino acid, which means our bodies cannot produce it: we must get it from food.
Interestingly, decreased tryptophan levels in the brain (and thus the synthesis of serotonin) increases bulimic urges (or depression) in bulimic and recovered bulimic individuals. (A similar study in AN patients have found that acute tryptophan depletion is anxiolytic – or anxiety reducing. Of course, one study is hardly enough – I know more have been done, but I need to read more about acute tryptophan depletion to get a better sense of where the consensus lies.)
And here we come across a hint as to why bulimia is more prevalent in females than males (and this likely extends to eating disorders more generally).
Furthermore, given disproportionate occurrence of bulimic syndromes in females, it is noteworthy that interventions aimed at lowering 5-HT activity (e.g., a 3-week calorie-reducing diet or acute tryptophan depletion) will produce greater alterations of 5-HT function or lowering of mood in women than in men (Goodwin et al. 1987; Young and Leyton 2002). In other words, dietary effects upon 5-HT activity seem to preferentially affect females.
There’s been a lot of studies trying to identify different variants (called polymorphisms) of genes involved in the serotonin pathway that are associated with eating disorders or traits known to involve serotonin (harm avoidance, neuroticism, impulsivity). These polymorphisms are different versions of a gene (think different eye colour or blood types). For example, alterations in a gene that makes the serotonin transporter protein – required to get serotonin back into the cell it was released from and stopping neurotransmission – may change how fast the protein uptakes serotonin back into the cell. So, effectively, regulating how much and how long serotonin gets to bind to the other cell, even if the same amount of serotonin is released, can lead to very different downstream effects in individuals with different versions of this gene.
I’m not going to bore you with all the findings, as they are generally inconsistent. (Suggesting serotonin influences many different traits and is not specific to any trait in particular.) But one thing that is clear is that people with bulimia (and those who have recovered from bulimia) have alterations in the serotonin system. In fact, it is also often altered in unaffected relatives of BN patients (not much surprise here).
[toggle title_open=”For the neuroscience nerds” title_closed=”For the neuroscience nerds” hide=”yes” border=”yes” style=”default” excerpt_length=”0″ read_more_text=”Read More” read_less_text=”Read Less” include_excerpt_html=”no”]Here are some more details on the alterations in the serotonergic system in BN:
“(a) reduced central 5-HT transporter availability in women with BN (Tauscher et al. 2001) or who have recovered from bulimic anorexia nervosa (AN) (Bailer et al. 2007);
(b) reduced 5HT2a receptor binding (in subgenual cingulate, mesial temporal, and parietal cortical regions) in women recovered from BN (Bailer et al. 2004);
(c) increased presynaptic 5-HT1A autoreceptor activity (in the dorsal raphe) of people recovered from bulimic-type AN, and in postsynaptic 5HT1A receptors in various brain regions in people with active BN (Tiihonen et al. 2004).”[/toggle]
Research on nonhuman primates has shown that a particular version of the serotonin transporter gene (the one that gets serotonin back into the releasing (or presynaptic) cell), termed the “low-function” allele, alters stress-response (and serotonin metabolism). The “implication is that developmental stress, in genetically susceptible individuals, can precipitate alterations in [serotonin] activity”. (Alleles are alternative forms of a gene – again, think blood types and eye color.)
Moreover, this research (which has the advantage of being prospective rather than retrospective) establishes that “developmental stress activates genetic propensities, and not that genetic propensities cause individuals to seek out stressful life situations, or otherwise ‘come to harm'”.
There is research in humans which suggests that carriers of this “low-function” allele, when exposed to stresses during childhood and adolescence (like maltreatment and/or abuse) are more vulnerable to suffer from depression, be more impulsive and be more disinhibited. Moreover, bulimic women with comorbid problems like anxiety and substance-abuse were also found to be more likely to have the “low-function” allele of the serotonin transporter gene.
Statistically, more likely strongly suggests that the “low-function” allele is strongly associated with an altered stress-response. BUT the fact that there are bulimicswithout comorbid anxiety and/or substance-abuse (and all the other aforementioned traits common in BN and AN-BP) illustrates that the “low-function” allele is not the whole story. It doesn’t “cause” these traits in the literal sense, but it may play a big role. In other words, it is part of the story.
Steiger et al. stress that “in the bulimic population, anomalies in [serotonin] activity are observed to predict severity of concurrent psychopathological trait manifestations far more consistently than they do for severity of bulimic symptoms… ”
So, what is the take-home message about the role of serotonin in bulimia nervosa and binge-purge type anorexia?
An implication is that [serotonin] alterations may not directly cause bulimic eating problems, but may rather indirectly influence susceptibility to bulimic syndromes, by heightening traits (such as affective instability or impulsivity) that play indirectly into risk. We also assume that abnormal [serotonin] status in bulimic individuals reveals an “end state” associated with diverse causal paths sometimes reﬂecting the cumulative effects of chronic dieting, sometimes a constitutional tendency based on heredity, sometimes the consequence of exposure to intense developmental or current stress, and sometimes a combination of all these things.
Of course, this has really important implications for treatment: individuals for whom abnormalities in the serotonin system are secondary (ie, consequences of dieting) might not require as extensive or prolonged treatment as those for whom serotonin dysregulation is more hereditary or for whom adverse events in childhood and adolescence might have activated the “low-function” serotonin transporter allele (or other genes in the pathway that may have the same end-result).
This is supported by a study (full text here) showing that traditional CBT seems to work well for bulimic patients with few psychiatric comorbidities but “enhanced” CBT is better suited for patients with a higher prevalence of psychiatric comorbidities.
In other words, the ultimate etiological model of the factors leading to disorders characterized by the presence of binge-eating and purging will come from “an understanding of the interplay among genetic factors coding for [serotonin] activity, environmental stresses that may amplify genetic susceptibilities, and environmental inducements toward dieting (which can be understood to indirectly reduce [serotonin] activity at a population level)”.. and this understanding will, hopefully, enhance the development and availability of more patient-specific treatment approaches.
Steiger, H.,, Bruce, K.R.,, & Groleau, P. (2010). Neural Circuits, Neurotransmitters, and Behaviour – serotonin and Temperament in Bulimic Syndromes Behavioural Neurobiology of Eating disorders , 125-138 DOI: 10.1007/7854_2010_88