Science has struggled to explain anorexia nervosa in its entirety. A new model is targeting the insula, a central hub of brain networks
Faulty thinking: The pitifully thin experience themselves as overweight
There is a common misperception, found among both professionals and laypersons, that anorexia nervosa is a lifestyle choice, typically of young middle-class females who are so obsessed with their weight and shape that they practise extreme dieting and self-induced vomiting. Although most common in females aged 15-35 living in westernised societies, anorexia nervosa is occurring increasingly often in developing countries; it can also affect males and those in younger and older age groups. And far from being a lifestyle choice it is in fact an extremely complicated and life-threatening illness with a poor prognosis. Roughly 66 per cent of patients appear to make a full and sustained recovery after five years but the lifetime mortality directly attributable to the illness is in the order of 10 per cent.
The disorder is riddled with misperceptions, mystery and paradox. The literal meaning of anorexia nervosa is “nervous loss of appetite”, but that is a misnomer. In reality it is a biologically-based illness in which the sufferer usually has a ravenous appetite, as well as a myriad of other features that cannot be explained by starvation alone. This is the mystery of anorexia nervosa.
Misperception is not confined to the unaffected; it occurs within the individual patient too. Patients with anorexia nervosa experience themselves as fat, even when they are very thin, a phenomenon known as body-image distortion. This is not a fabrication on their part, but a genuine misperception, which has been clearly demonstrated in numerous empirical studies-using mirrors, cut-out paper silhouettes and morphable computer images. A recent study has shown that when walking towards a narrow door, through which it is possible to walk directly, people with anorexia nervosa tend to turn their bodies sideways to go through the door, compared with healthy controls who have no such need, even though they are far less thin.
Body-image distortion is only one of many complex and mysterious features of this illness. Other features of anorexia nervosa include: severe anxiety, an intense preoccupation with weight and shape, dread of weight gain, mood disturbance, self-loathing, obsessive-compulsive behaviour and a raised pain threshold. In addition, thought processes are often impaired. Sufferers may display a disconnection between thoughts and feelings, rigidity of thinking, difficulty inhibiting intrusive thoughts and weak central coherence. The latter refers to the fact that attention to fine detail is so pronounced in patients with anorexia nervosa that they lose sight of the big picture: they cannot see the wood for the trees. Numerous psychological tests demonstrate this. For example, when people with anorexia nervosa look at a complex diagram which contains a basic shape, such as a rectangle, in its centre, they cannot see the rectangle and focus only on the complexities of the diagram.
It is illogical-and unsupported by the evidence-to attribute these features to malnutrition alone. They are, very likely, genetically determined. Unaffected first-degree relatives often exhibit the very same characteristics and research suggests that, in sufferers, they predate the onset of the illness and many persist despite the restoration of good physical health.
How these features occur is a mystery, a mystery compounded by the fascinating paradoxes inherent in the illness. Patients feel fat when they are thin. They feel well when they are unwell. They behave with great strength despite their obvious fragility. They feel full when they are empty. They starve themselves but some also binge. They have extraordinary control over themselves and their environment but feel they have no control. Before being ill they have been conscientious, compliant children, but when ill they are defiant and rebellious. They experience the illness as a comfort and a refuge, yet are clearly tormented by it. Finally, they experience our attempts to help as coercive: at times they have insight and wish to recover, at others they are oblivious to their illness and desperately resist treatment.
Many attempts have been made to explain the mystery and paradoxes of anorexia nervosa. However, none so far has fulfilled the criteria required for a complete explanation: empirically derived, refutable, specific to the illness, necessary and sufficient to account for the development of the illness and its various manifestations. Research conducted by our team and others over several years has led us to propose a model based on neuroscience that purports to fulfil all these criteria.
In the development of anorexia nervosa we fully accept the contribution of pregnancy complications that may affect foetal brain development, environmental factors such as sociocultural pressures to be thin, the onset of puberty with its associated body changes and other external stressors. However, these are insufficient to explain the illness in its entirety. A series of studies by our colleagues, and others, have produced convincing evidence of a significant genetic contribution.
Our model is based upon an interaction between environmental factors and a specific genetic profile, which is up to 11 times more likely to be present in those with anorexia nervosa than those who are unaffected. This profile is characterised by the dysfunction of various neurotransmitter systems and, specifically, noradrenaline. The chemical messenger, noradrenaline, has a number of important functions: it regulates the sympathetic nervous system (fight or flight responses), blood flow to the brain and neuroplasticity (the ability of the brain to change and adapt to environmental requirements). When the noradrenaline system is overactive, as proposed in our model, anxiety levels are very high, blood flow to specific brain structures is subtly, yet significantly, reduced and the neuroplasticity of these structures is impaired.
One specific structure-the insula-is vital to all of the above. The insula is at the centre of many brain networks. It is so crucial to the transmission of information that it can be likened to the central hub of the brain-many crucial routes pass through it. Of particular relevance to anorexia nervosa is the insula’s role in sensitivity to stimuli originating inside the body (interoception); the brain’s pictorial representation or map of the body (bodily representation); regulation of the sympathetic nervous system; perception of pain; the regulation of disgust and the integration of thoughts and feelings. Since all these functions are impaired in anorexia nervosa, insula dysfunction could account for the numerous features of the disorder.
Our clinically-based genetic, neuroimaging and neuropsychological studies all support this insula model. For the moment we are intrigued by the idea that a combination of genetic and environmental influences may upset the regulation of the noradrenaline system, prompting a cascade of events that culminates in dysfunction of the insula. The latter subsequently leads to a failure of information processing, then to body-image misperception and intense body-focused anxiety, finally resulting in the condition we call anorexia nervosa.
Should this model prove to be correct, it could revolutionise the treatment of anorexia nervosa with the potential for a far better prognosis.