Authors: Sietske G. Helder, Ricardo Sainz-Fuertes, Frederique Van den Eynde, Anna V. Oldershaw, Janet Treasure, Iain C. Campbell, Simon Lovestone, Ulrike Schmidt, David A. Collier
Centre: Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK

Short Description

Genetic biomarkers

Genetic profiles may influence vulnerability of developing an eating disorder, affect the age of onset, severity, response to treatment, relapse, etc. Identifying associated genes is important to study the mechanism of disease in order to improve and tailor treatment. It will be an important contribution to translational research in this area.

A number of candidate genes have been identified from single-gene studies or the use of linkage data to identify positional candidates. Of particularly interest is the brain serotonin (5-HT) system, considerable evidence suggests that altered serotonin function contributes to dysregulation of appetite, mood, and impulse control in eating disorders (Kaye, 2008). We will also focus on the opioid and dopamine brain systems, which have been implicated in appetite control and associated with eating disorders (Brown et al, 2007; Palmiter, 2007).

Currently most studies use categorical diagnosis. An increasingly popular approach in psychiatry is to investigate underlying cognitive and behavioural traits, or endophenotypes (Gottesman & Gould, 2003). An endophenotype should be heritable and trait independent; thus they provide a more direct association with genotype than the phenotype. Our group has identified three potential endophenotypes; poor cognitive flexibility (set-shifting), weak central coherence (detail focus), and obsessive-compulsive traits. We will include these endophenotypes in our genetic analyses.

Proteomic and gene expression biomarkers

Proteomic research aims to identify differences in proteins in accessible tissues, such as blood, which can be used as biomarkers. The study of biomarkers in eating disorders is a new venture. A biomarker is an indicator of a change in a biological state e.g. a change in expression or state of a protein that correlates with the risk or progression of a disease. Biomarkers can include differences in RNA, DNA, peptide, small molecule or even behavioural measures. A biomarker could be used to diagnose disease risk, improve diagnostic accuracy, identify (sub)types of eating disorders in order to tailor treatment and it would aid monitoring of disease phase, the latter being of particular importance in clinical trials (Lovestone, 2007).

Key references:

• Wade, Bergin, Tiggemann, Bulik, & Fairburn, Aust N Z J Psychiatry Feb;40(2):121-8, 2006
• Kaye, Physiol Behav, Apr 22;94(1):121-35, 2008
• Collier & Treasure, Br J Psychiatry Nov;185:363-5, 2004
• Brown et al, Biol Psychiatry Feb 1;61(3):367-73, 2007
• Palmiter, Trends Neurosci Aug;30(8):375-81, 2007
• Gottesman & Gould, Am J Psychiatry Apr;160(4):636-45, 2003
• Lovestone, Expert Rev Proteomics Apr;4(2):227-38, 2007

Current Status

November 2008

We are currently finishing a pilot study comparing current AN patients to recovered AN patients and healthy controls. We are following up these results in a longitudinal case-only study. We conduct a proteome-wide analysis of AN, aimed at identifying new protein biomarkers of the disease. Blood plasma was analyzed by two-dimensional gel electrophoresis and mass spectrometry, using methods that have proved useful in proteomic studies of Alzheimer's disease (Hye et al, Brain, 2006).