Two Lessons From Anorexics

What Eating Disorders Tell Us About our Our Drive to Eat

Back when I used to see clients for one-to-one nutrition advice, one of my regulars was a young lady with anorexia nervosa (AN). I’m not sure how effective I was at helping Sarah*, but I did at least succeed in supporting her with sufficient micronutrition. Sarah’s father was the cliché ultra-busy multi-millionaire whose work came first, family a distant second. She had a strained relationship with her mother but was close with her two sisters. She was incredibly intelligent and it always struck me as odd that she appeared to have so much energy, despite an extremely restricted calorie intake. While I was unable to hypothesise where this energy came from, it was clear to me that neurochemically there’s a bunch of stuff going on in the brains of young adults like Sarah that’s somewhat different to those of us with more regular eating behaviours. As it turns out, I might have been on to something, as two areas of research into anorexia might help us to not only learn how to help those with the condition, but also understand eating behaviour more generally.

AN is a condition characterised by self-starvation and distorted body image. It’s concerningly common among adolescent females as well as a growing number of males, with up to four percent of females and 0.3 percent of males suffering from AN during their lifetime in Western nations [1]. Individuals with AN constantly worry about how much body fat they have, despite being dangerously thin, and obsess about how much food they consume. Because of the devastating effects of this condition, scientists have long sought to understand the mechanisms underlying these individuals’ decreased motivation to eat. As it happens, in doing so, exciting insights into eating behaviours have been revealed.

When Things Go Wrong: Lack of Motivation to Eat

From motivation to reward, dopamine might be the most hyped of all the body’s chemicals. As discussed in The Craving Elephant, through its association with anything from sex to food, this neurotransmitter is responsible for driving us to seek out things we previously found pleasurable [2]. Indeed, dopamine has emerged as a fundamental component in the complex interplay of competing signals behind what motivates us to eat. Yet, any analysis is based on the assumption that our drive to eat requires large amounts of excitatory signals to suppress inhibitory cues derived either from our body or the environment around it. At times, however, these excitatory, motivational signals can be overridden, and scientists think that this mechanism forms the basis of some eating disorders, as anorexics can function without eating for days despite large caloric deficits. However, understanding this has proven to be particularly problematic due to the inherent difficulty in determining whether any observed change in the brains of these patients is a cause or consequence of starvation.

Any form of restrictive dieting can lead to considerable psychological changes such as increased anxiety, depression and a diminished libido. One of the more dramatic examples of this comes from the famed Minnesota Starvation Experiment conducted in healthy volunteers during World War II [3]. Subjects were confined to a designated living area for several months, during which scientists monitored changes in their metabolism in response to starvation. One of the most striking findings was that individuals on long-term calorie-restricted diets were found to be ravenously hungry. And not just the type of hunger that reminds us to saunter over to the fridge and grab a leftover sandwich, either. Subjects literally obsessed over food to the extent that some had to be transferred to a psychiatric ward [4].

Similar to the Minnesota subjects, people with AN exhibit a wide range of obsessive-compulsive behaviours, together with a reduced ability to experience pleasure and reward. Brain imaging studies in these patients have revealed profound alterations in their dopaminergic food reward system, which may help to explain why they’re remarkably insensitive to food stimuli [5]. However, as highlighted, it could be argued that changes in their reward system occur as a consequence of food restrictions. Yet, data on the hypofunctioning dopamine system of obese individuals seem to support these findings, and it’s becoming increasingly clear that changes in eating behaviour can have long-lasting effects on neural circuits [6]. In the context of anorexics, as these behaviours are learned through reinforcement – i.e. prolonged dieting – they start to become so deeply entrenched in their lives that a few familiar cues – such as the initiation of a meal – can lead to a series of ritualised behaviours and reduced eating. You might be thinking that food cues suppressing your motivation to eat seems counterintuitive, since humans are wired to respond to reinforcing, motivating food-related prompts in the external environment. However, something unusual takes place in the brains of individuals affected by anorexia. These patients seem to be less responsive to the kinds of food cues that would be highly appetising for most of us. Although it’s not clear why their processing of food stimuli is altered, an influential hypothesis suggests that when anorexics are hungry, they focus less of their attention on food stimuli than healthy individuals [7]. Attention plays a pivotal role in directing sensory and cognitive processing, which influences behaviour. It might be that reduced attention to food stimuli in anorexics predisposes them to resisting food and maintaining fasting. Given the prominent role that food-related cues have played in evolution, why do anorexics direct their attention away from them? As satisfying hunger feels so good both physically and emotionally, scientists have long wondered how anorexic patients can ignore the rewards typically associated with eating.

The answer may lie in a series of experiments carried out over the last three decades. These experiments show that anorexics not only disengage with food cues, but perceive them as “threat-related” stimuli. Unlike healthy individuals, anorexics display increased activation of a region of the brain known as the anterior cingulate when looking at images of food. This region is implicated in evaluating the emotional valence of objects in the environment, as well as attentional control. The increased activation of the anterior cingulate in anorexia suggests that looking at food cues triggers anxiety in these individuals as opposed to positive emotions [8]. One study also found that, while consuming a meal releases copious amounts of dopamine in the brains of healthy individuals, increased dopamine release might be a source of anxiety for anorexics, as opposed to a source of pleasure [9]. Because humans are evolutionarily wired to avoid potentially threatening stimuli, anorexic patients seek to minimise exposure to these stimuli by directing their attention away from them. With time, the abnormal processing of food-related stimuli reinforces this maladaptive behaviour, explaining their desire to pursue dietary restrictions as well as their remarkable insensitivity to homeostatic hunger signals.

Lesson 1: Motivation for Feeding

The evidence provided by people with anorexia suggests that altered activity in key neural circuits encoding the valence of food stimuli can sabotage deeply ingrained food reward mechanisms, which in turn can curb our motivation to eat. What this tells us is that some motivational aspects of human eating behaviours are closely aligned with psychological states. Dopamine seems to play a fundamental role in reinforcing eating behaviour in healthy individuals, but, as we have seen, increased dopamine in anorexics may make them less willing to eat, even when food is available. This makes perfect sense when we think about what’s happening when individuals with AN see food. Through repetition, their brain has learned to associate the taste, sight, smell, texture and sound of food with a threat to the thing that stresses them most: their body weight. For a person with anorexia, every bite is as stressful as the first, which is why they reduce their food consumption to a minimum. Bearing in mind that, like most pathologies, AN is not an all-or-nothing event, these findings also help explain why some of us, when we feel anxious, might sometimes choose to swerve certain foods.

Inhaling Love

Another chemical is unexpectedly, but crucially, involved in our food intake. Oxytocin, a hormone synthesised in the hypothalamus, is known for its effects on social bonding, lactation and maternal behaviour [10]. This “love” chemical also plays a central role in the neural circuits controlling appetite, body weight and food intake [11]. Oxytocin does this by helping entwine appetite with social bonding. Elegant experiments in rodents have even demonstrated that pumping oxytocin directly into the brain can override those food reward mechanisms, silencing the urge to eat certain foods [12].

It’s what happens when the levels of this hormone reach unusually low levels that a chunk of recent research on eating behaviour has been focussed. Given its role in sparking interpersonal interactions, scientists have begun to ponder whether reduced oxytocin may explain bonding difficulties in patients with eating disorders. As noted, a key feature of patients with eating disorders is their reluctance to engage in social behaviours. Although this trait is well documented in the scientific literature, a flurry of potential mechanisms have been suggested to explain it. Among those, the idea that low levels of oxytocin may predispose individuals to emotional difficulties is currently riding high.

The evidence starts with neonates, where bonding activity takes place around breastfeeding. Breastfeeding is one of several activities that ensure emotional attachment in human infants towards their mothers and could be viewed as a distant forebear of social eating in adult life. The act of eating together is a ritual that brings benefits beyond the immediate satisfaction of basic human needs – i.e satiating your hunger comes with the added bonus of forming connections with people around you. From a scientific perspective, the manifestation of these repeated “attachment” behaviours is crucial in childhood as they gradually become engrained in the memory system, allowing the child to develop internal working models of how to interact with the rest of the world. This is why some scientists feel that when this attachment behaviour is repressed or disrupted in early life, people may go on to develop eating disorders in adulthood. Oxytocin is released during breastfeeding and is thought to prop up early mother-child interactions by fostering sensitivity and synchrony. Although evidence is still meagre, some scientists contend that adverse attachment events in early life may lead to dwindling oxytocin levels and increased vulnerability to eating disorders. Why? As far as the theory goes, adverse attachment experiences – i.e. failure to establish an early bond with your mother – in early life may trigger an increased stress response, paving the way to long-term emotional instability and eating difficulties later in life [13].

Although the literature on the link between oxytocin, early maternal behaviour and eating disorders is sparse, studies on individuals with AN are starting to paint a compelling picture. Anorexics often experience a profound sense of alienation from their community, which leads them to develop anti-social behaviours. Some of these difficulties arise from problems in their attentional processing and manifest in excessive attention to negative body shape stimuli – not surprisingly, teasing, body shaming and bullying are suggested to trigger the onset of this illness [14]. To test whether oxytocin could clear out these negative thoughts, a group of scientists offered intranasal oxytocin – the only way into the brain for oxytocin given that this peptide cannot cross the blood brain barrier [15] – to some AN patients before showing them a range of different images [16]. These images varied in content from faces expressing different emotions (like anger and disgust) to succulent, highly caloric food. Under normal circumstances, individuals with AN would avidly cling to images of negative stimuli – their brain being wired to steer away from positive facial expressions. However, the study showed that the jazzy, oxytocin-tinged sniff made individuals more likely to avoid angry faces and pay less attention to negative eating-related stimuli. This is not surprising given that a similar effect has been observed in other disorders with impairments of social function, such as schizophrenia, autism and depression [17]. What is surprising is that the neurological underpinnings of anorexia differ greatly from these disorders, with the only commonality being persistent and marked social withdrawal. What, then, is the science behind this seemingly magical stardust?

As it turns out, people with AN have abnormally low levels of oxytocin [18], to the extent that the lower the levels of oxytocin in some patients, the more severe their eating disorder [19]. But here’s the thing. Among its other functions, oxytocin is known to decrease cortisol levels, which, in anorexics, tend to be particularly elevated [20]. Cortisol is produced in response to stress, and lower levels of oxytocin are thought to facilitate cortisol spikes in anorexics. As a result, an increasing amount of attention is being directed to the cortisol-dampening action of oxytocin in the hope that it may one day lead to new strategies to reduce anxiety and stress in individuals with AN, subsequently alleviating the effects of their eating disorder [21].

Positive findings from several research groups have led to fast-spreading enthusiasm among scientists [22]. However, if you do happen to have AN and are thinking of popping to your GP to get some oxytocin pills (synthetic oxytocin is FDA-approved), hold your horses. More recent studies on emotional recognition showed that oxytocin does not lead to any sizeable improvement in anorexia patients [23], and questions remain surrounding the optimal dose of oxytocin required to achieve the maximal effect [24]. In the context of emotional recognition, the lack of effect in patients with AN continues to baffle researchers, leading some to hypothesise that levels of oxytocin are so low in these patients that it cannot be recovered quickly – a finding plausibly connected to evidence of poor maternal behaviour in patients with AN.

Lesson 2: Eating in the Company of Others

I’ve described the effects of diminished levels of oxytocin in people with AN, but what does this emerging picture tell us about non-anorexics and their drive to eat? The implication of the function of oxytocin in social cognition and eating behaviour provides scientific validation of the influence of social bonding and eating meals in the company of others on our wellbeing. It also serves to emphasise the importance of family meals on children’s development. Studies in this area are ongoing and greater scrutiny on its mode of action, as well as the impact of intraindividual, interindividual and contextual factors will be required in order to have a more robust picture. Nevertheless, these findings help to provide confirmation of the benefits that interacting with others around food has on our wellbeing.

Postscript

This article was another co-written by Marco Travaglio. Marco holds a PhD in Neuroscience and is passionate about health and nutrition.

* Sarah is not her real name.

References:
1. Van Eeden, A. E. et al. (2021) ‘Incidence, Prevalence and Mortality of Anorexia Nervosa and Bulimia Nervosa’, Current Opinion in Psychiatry, 34(6), 515-24.
2. Collier, J. (2023) ‘The Craving Elephant’, Thought for Food, 25 May. Available at: https://jamescollier.substack.com/p/the-craving-elephant (Accessed: 15 September 2024).
3. Keys, A. et al. (1950) The Biology of Human Starvation. St. Paul, MN: University of Minnesota Press.
4. Baker, D. B. and Keramidas, N. (2013) ‘The Psychology of Hunger’, Monitor on Psychology, 44(9), 66.
5. Santel, S. et al. (2006) ‘Hunger and Satiety in Anorexia Nervosa: fMRI During Cognitive Processing of Food Pictures’, Brain Research, 1114(1), 138-48.
6. (a) Stice, E. et al. (2008) ‘Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele’, Science, 322(5900), 449-52; (b) Mahapatra, A. (2010) ‘Overeating, Obesity, and Dopamine Receptors’, ACS Chemical Neuroscience, 1(5), 346-7.
7. ibid (5).
8. Cowdrey, F. A. et al. (2011) ‘Increased Neural Processing of Rewarding and Aversive Food Stimuli in Recovered Anorexia Nervosa’, Biological Psychiatry, 70(8), 736-43.
9. Grzelak, T. et al. (2017) ‘Neurobiochemical and Psychological Factors Influencing the Eating Behaviors and Attitudes in Anorexia Nervosa’, Journal of Physiology and Biochemistry, 73, 297-305.
10. Viero, C. et al. (2010) ‘REVIEW: Oxytocin: Crossing the Bridge Between Basic Science and Pharmacotherapy’, CNS Neuroscience & Therapeutics, 16(5), e138-56.
11. Lawson, E. A. (2017) ‘The Effects of Oxytocin on Eating Behaviour and Metabolism in Humans’, Nature Reviews Endocrinology, 13(12), 700-9.
12. Mullis, K. et al. (2013) ‘Oxytocin Action in the Ventral Tegmental Area Affects Sucrose Intake’, Brain Research, 1513, 85-91.
13. Connan, F. et al. (2003) ‘A Neurodevelopmental Model for Anorexia Nervosa’, Physiology & Behavior, 79(1), 13-24.
14. Sharpe, H. et al. (2013) ‘Is Fat Talking a Causal Risk Factor for Body Dissatisfaction? A Systematic Review and Meta-Analysis’, International Journal of Eating Disorders, 46(7), 643-52.
15. ibid (10).
16. (a) Kim, Y. R. et al. (2014) ‘The Impact of Intranasal Oxytocin on Attention to Social Emotional Stimuli in Patients with Anorexia Nervosa: A Double Blind Within-Subject Cross-Over Experiment’, PloS One, 9(6), e90721; (b) Kim, Y.-R. (2014) ‘Intranasal Oxytocin Attenuates Attentional Bias for Eating and Fat Shape Stimuli in Patients with Anorexia Nervosa’, Psychoneuroendocrinology, 44, 133-42.
17. Jones, C. et al. (2017) ‘Oxytocin and Social Functioning’, Dialogues in Clinical Neuroscience, 19(2), 193-201.
18. Maguire, S. et al. (2013) ‘Oxytocin and Anorexia Nervosa: A Review of the Emerging Literature’, European Eating Disorders Review, 21(6), 475-8.
19. Lawson, E. A. et al. (2012) ‘Oxytocin Secretion Is Associated with Severity of Disordered Eating Psychopathology and Insular Cortex Hypoactivation in Anorexia Nervosa’, Journal of Clinical Endocrinology & Metabolism, 97(10), e1898-908.
20. ibid (13).
21. (a) ibid (17); (b) Hasselbalch, K. C. et al. (2020) ‘Potential Shortcomings in Current Studies on the Effect of Intranasal Oxytocin in Anorexia Nervosa and Healthy Controls – A Systematic Review and Meta-Analysis’, Psychopharmacology, 237, 2891-903.
22. ibid (21b).
23. (a) Leppanen, J. et al. (2017) ‘The Effects of Intranasal Oxytocin on Smoothie Intake, Cortisol and Attentional Bias in Anorexia Nervosa’, Psychoneuroendocrinology, 79, 167-74; (b) Leppanen, J. et al. ‘Meta-Analysis of the Effects of Intranasal Oxytocin on Interpretation and Expression of Emotions’, Neuroscience & Biobehavioral Reviews, 78, 125-44.
24. ibid (17).