Understanding the Science of Starving with Dr. Allan Kaplan

Understanding the Science of Starving with Dr. Allan Kaplan

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Dr. Allan Kaplan
Vice Dean, Graduate and Academic Affairs, and Professor of Psychiatry, Faculty of Medicine
Senior Clinician/Scientist, Center for Addiction and Mental Health
Full Member, Graduate Faculty, School of Graduate Studies, Institute of Medical Science

By: Parnian Pardis
Photo by: Dorsa Derakhshan

One encounter with a patient catapulted Dr. Allan Kaplan into a lifetime of researching and treating individuals with eating disorders. Inspired by Dr. Paul Garfinkel, Dr. Kaplan transferred from Internal Medicine into Psychiatry during his first year of residency with the Royal College. “The rest was history,” says Dr. Kaplan. Many years later, Dr. Kaplan is now the Vice Dean of Graduate Academic Affairs and Professor of Psychiatry at the University of Toronto, as well as Senior Clinician Scientist at the Centre for Addiction and Mental Health.

“Anorexia [nervosa] has been in the medical literature for at least 400-500 years. It’s been mislabeled through the course of history, but the core illness and symptoms have stood the test of time,” asserts Dr. Kaplan. Struck by the complexity of anorexia nervosa, Dr. Kaplan contemplated how the brain allows individuals to survive despite self-induced starvation. In 1995, Dr. Kaplan and colleagues were approached by Madame Price with an exciting proposition that shaped the “Price Study” during a scientific meeting in Switzerland. The relationship between anorexia nervosa and an underlying genetic process had yet to be established. With subsequent funding from Madame Price and the National Institute of Health, research of its genetics was made possible. The Eating Disorders Working Group of the Psychiatric Genomics Consortium conducted the first genome-wide association study (GWAS) of anorexia nervosa.1 This GWAS of 12 case-control cohorts, including 3 495 anorexia nervosa cases and 10 982 controls, identified a locus on chromosome 12 (rs4622308) as a common genetic variant associated with anorexia nervosa.

Amy Miles, a Doctoral student under the supervision of Dr. Kaplan, investigated this further. Fat loss from the body is accompanied by fat loss from the brain—white matter architecture is disrupted because myelin in the brain is composed entirely of lipid molecules.2,3 Using diffusion tensor imaging (DTI), Miles analyzed the integrity of white matter in four groups of females: 1) underweight at time of imaging; 2) anorexia nervosa recoverees; 3) healthy siblings of individuals in the first group; and 4) unrelated healthy controls.

Interestingly, abnormalities in white matter architecture were identified within all but the unrelated healthy controls. This result suggests permanent “scarring” in recoverees from anorexia nervosa and alludes to the inheritance of a genetic predisposition to anorexia nervosa in healthy sibling controls. “This is the first study to show that there are abnormalities in this group of healthy siblings…so what is inherited and what’s the impact of that?” asks Dr. Kaplan. Impaired cognitive functioning has reported in individuals diagnosed with anorexia nervosa. As a follow-up, Miles is employing neuropsychological tests to evaluate subjects’ cognitive function and explore the manifestation of this genetic predisposition.

Ultimately, anorexia nervosa “is not just a cultural problem,” states Dr. Kaplan. Recognizing its neurobiology destigmatizes this eating disorder and prevents parents from assuming responsibility for its cause. Parents can become better equipped to combat the genetic risks by shaping the environment for their daughters. Encouraging kids to partake in activities that will enhance their self-esteem becomes essential.

The next step in anorexia nervosa research is to identify which genes are responsible for these white matter abnormalities. With this knowledge, there is the potential to repurpose drugs for the management of anorexia nervosa. However, these large-scale studies cannot be conducted alone. Dr. Kaplan emphasizes the need for collaboration as he also works with groups around the world to receive DNA samples. He also reiterates several times during our interview that research is a long journey. Although faced with setbacks, the team persevered and found what they believe is irrefutable evidence signaling genetic risk for anorexia nervosa. “And we’re still not there, but we’re getting a lot closer,” says Dr. Kaplan.

References

  1. Duncan L, Yilmaz Z, Gaspar H, et al. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa. Am J Psychiatry. 2017;174(9):850-858.
  2. Swayze VW, Andersen AE, Andreasen NC, et al. Brain tissue volume segmentation in patients with anorexia nervosa before and after weight normalization. Int J Eat Disord. 2003;33(1):33-44.
  3. Travis KE, Golden NH, Feldman HM, et al. Abnormal white matter properties in adolescent girls with anorexia nervosa. Neuroimage Clin. 2015;9:648-659.