Tara Chowdhury, Contributing Writer
Thin is beautiful. This mantra has been blamed for the prevalence of anorexia nervosa (AN) among teenaged girls in the western world. Far from beautiful, the symptoms of the disease include body image distortion, over-exercise, irrational fear of weight gain, and trouble enjoying the taste of food. Since the mechanisms of the disease are poorly understood, AN is not reliably treatable and, sadly, has one of the highest mortality rates among psychiatric illnesses. AN is most common among adolescent girls, especially those who suffered from anxiety disorders during childhood. This pattern suggests that the disease may be triggered by the hormonal surges that accompany puberty. It is possible that AN onset may be driven by hormones in the developing brain that alter the brain response to stress.As with most psychiatric illnesses, there are many brain areas that may contribute to AN. Lack of appetite may be caused by problems in circuits of the hypothalamus that regulate feeding behavior. Difficulty taking pleasure in eating indicates problems in processing rewards, which could be caused by abnormal dopamine signaling in the striatum. Irrational fears of weight gain suggest involvement of the amygdala. Circuits in the prefrontal cortex regulate the self-control that individuals with AN use to create dietary rules and restrictions. Anxiety is regulated in part by the hippocampus, which makes connections with many of the brain regions mentioned above. Total brain and gray matter volumes are reduced in patients with AN, and functional imaging shows that their brain activity is different from healthy controls while viewing images of bodies or food. It is unclear whether these differences are responsible for or caused by the disease, so scientists have developed animal models to study the neurobiological basis of AN.
I am studying a rat model of this disease that mirrors some of the behavioral symptoms of anorexia nervosa. When rats are given access to a running wheel, they naturally show interest in running. When these rats are put on a restricted schedule of food access, paradoxically, they begin to run even more and lose weight dramatically. This model is called Activity-based Anorexia (ABA). While these animals do not show the same self-starvation behavior as humans, the paradoxical hyperactivity is an interesting parallel to the over-exercise exhibited by patients. This is thought to be an example of stress-induced anxiety. Using this animal model, my research goal is to understand some of the neural mechanisms that are responsible for AN by studying areas of the brain that are responsible for anxiety-like behaviors.
My research focuses on the role of the hippocampus in the rodent model of AN. The hippocampus is part of the limbic system, popularly known as the ‘emotional’ brain. The hippocampus is involved in mediating anxiety, which is a normal response to stress. In females, this brain region undergoes changes during puberty, in response to hormonal fluctuations. The result is that the hippocampus becomes more responsive to stress, which can drive increases in stress-induced anxiety in pubertal females. Since pubertal females comprise the majority of the population with AN, it is possible that the hippocampus plays a role in their vulnerability to this disease.
Using the ABA rat model, I have discovered that the hippocampus is not uniformly affected. The two ends of the hippocampus, called the dorsal and ventral hippocampus, respond in opposing ways. In the ventral hippocampus, the portion that is involved in anxiety behaviors, neurons have more dendrites and more total dendritic length after ABA. In the dorsal hippocampus, the region that supports spatial learning and memory, neurons have reduced dendritic [JZ1] length and fewer branches after ABA. My current experiments will test how these anatomical changes translate into changes in hippocampus-dependent behaviors, such as spatial learning abilities and anxiety-like behaviors. Dorsal hippocampus atrophy suggests that the animals will have impaired spatial learning abilities, and increased anxiety levels may result from ventral hippocampus growth.
AN patients suffer from a high rate of relapse, and many people recovering from AN claim that aspects of the disease still plague them, especially when they are experiencing stress. In light of this troubling aspect of AN, I am also studying recovery after ABA. Following four days of ABA, the rats are allowed to recover for a week by removing the running [JZ2] wheel and giving free access to food. In normal rats that are not exposed to the ABA paradigm, the ventral hippocampus continues to develop after puberty in the rat. There is a period of rapid growth of neuronal dendrites, followed by a retraction of dendrites that occurs during adolescence, the period between puberty and full adulthood. In rats that endured ABA soon after puberty, the dendritic growth spurt occurred earlier than age-matched controls. Together these findings suggest that the combination of exercise and food restriction stress causes the ventral hippocampus to develop more rapidly in the rats that experience ABA. I am currently testing how this premature growth spurt affects the behavior of the adult rat after recovery from ABA. Based on the anatomy alone, I expect to find that recovered ABA animals have similar levels of anxiety to the control animals. However, behavior may be altered by changes at the cellular or network level that are not reflected by the gross anato[JZ3] my.
These results show for the first time that the hippocampus continues to develop dramatically after puberty. This developmental period may cause the brain to be more vulnerable to disorder during adolescence. My research has shown that during adolescence, the hippocampus is affected in different ways by exercise, food restriction, and ABA, the combination of the two. These results suggest that the hippocampus may play a key role in the onset of AN in adolescents.
Adolescence is often a period in which people engage in more risky behaviors in preparation for leaving the nest. It is a period during which the brain is continuing to develop and mature. Experiences as common as exercise and food restriction have effects on the developing adolescent brain, and these experiences may cause long lasting changes in the way the brain functions. Perhaps teaching children an awareness of their habits and feelings will equip them to recognize symptoms of disorder in themselves and their peers. While we search for better treatments for AN, prevention and early diagnosis are the best defenses.
Chowdhury, T. G., Barbarich-Marsteller, N. C., Chan, T. E., & Aoki, C. (2013). Activity-based anorexia has differential effects on apical dendritic branching in dorsal and ventral hippocampal CA1. Brain Structure and Function, 1-11.
Tara Chowdhury is a contributing writer.