There is a lot we still don’t know about anorexia nervosa, but we do know that the disorder has a profound impact on the body – from the heart, to the bones, to the elaborate hormone system. We also know that anorexia nervosa is a neurobiological disorder, in that it is a disorder in the system involving thinking and action. A disorder being neurobiological also means that it is likely influenced by genetic, metabolic, and/or other biological factors.
Similar to many other avenues of research, scientists interested in the neurobiology of anorexia nervosa design studies in which individuals with and without the disorder are compared. These studies attempt to identify brain regions and circuits that may increase vulnerability to, or perpetuation of, anorexia nervosa. Various structural differences have been explored, including
- the volume of brain tissue (meaning, the size of different parts of the brain),
- the shape of certain brain structures, and
- anatomical connections between different brain regions.
Studies do indicate structural brain differences between those with and without the disorder. However, the specific regions of the brain, as well as the direction of differences (more or less compared with healthy peers), tends to be variable between studies. Interpreting the current collection of evidence is further complicated by differences in study design that could contribute to the inconsistency across findings.
Studies that have looked at global differences in the brain – meaning “brain-wide,” rather than within certain areas – paint a more consistent picture. For example, several studies have investigated the volume of grey matter across the brain. Grey matter refers to the brain tissue composed of neuron cell bodies. One relatively robust finding is that the volume of grey matter in the brains of acutely ill individuals with anorexia nervosa who are underweight is reduced, as compared to individuals without the disorder. A reduction in the thickness or volume of the cerebral cortex (the outer layer of brain tissue) has also consistently been observed in the low weight state.
Do these differences contribute to the development of anorexia nervosa? Or, are they a consequence of illness? Or a consequence of being at a low body weight? Researchers have tried to answer these questions in two ways:
- Individuals with the disorder have been followed as they gain weight, with grey matter measured over time.
- Individuals with anorexia nervosa have been compared to those with the disorder who are in remission or recovery (and maintaining a healthy weight), and a healthy comparison group with no history of anorexia nervosa.
Current data suggest that grey matter volume increases shortly after weight restoration and that the changes in the brain are explained by weight increases, as opposed to alternative factors. Encouragingly, a number of studies have found among those who have sustained health for a longer period of time, grey matter volume across the brain is comparable to that of those who have never had the illness.
The cause of the changes in grey matter volume during acute anorexia nervosa remains unclear. One hypothesis is that grey matter volume changes as a consequence of dehydration and then normalizes with rehydration. It is also possible that there are more substantial structural changes to the neurons in the setting of starvation, and that these changes manifest as altered volume in grey matter. Another possibility is that starvation leads to changes to other types of cells that are contained in grey matter volume, or even to cell death.
The effects of changes in brain volume on cognitive function and psychological symptoms such as anxiety and depression – both immediate and long-term – in anorexia nervosa are unclear. However, the evidence of the reversal of starvation effects on brain volume with weight restoration is very encouraging. So too is the finding that grey matter recovery occurs with weight improvement regardless of illness duration. Indeed, the best current predictor of brain volume recovery is change in weight – providing yet another incentive to reach and maintain a healthy one!
Answering questions about grey matter in anorexia nervosa, of course, leads to more questions about the structure and function of the brain, and the role of these biological variables in the illness. What about the white matter – the part of the brain that includes the cell axons (that connect neurons) and their protective covering? What about how the different parts of the brain are connected, and how they function? We have several ongoing studies examining these questions, both looking at differences between groups with and without anorexia nervosa, and following patients with anorexia nervosa over time. We hope this work will contribute to answering these questions, and lead us to the next important investigations.