10 Laurin N, Ickowicz A, Pathare T, Malone M, Tannock R, Schachar R et al. J Psychiatric Res 2006; doi:10.1016/j.jpsychires. 2006.10.010. 11 Dorval KM, Wigg KG, Crosbie J, Tannock R, Kennedy JL, Ickowicz A et al. Genes Brain Behav 2006; doi:10.1111/j.1601-183X.2006. 00273.x. 12 Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M et al. Mol Psychiatry 2005; 10: 944–949. 13 Hawi Z, Dring M, Kirley A, Foley D, Kent L, Craddock N et al. Mol Psychiatry 2002; 7: 718–725. 14 Smoller JW, Biederman J, Arbeitman L, Doyle AE, Fagerness J, Perlis RH et al. Biol Psychiatry 2006; 59: 460–467. Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa Molecular Psychiatry (2007) 12, 229–230. doi:10.1038/sj.mp.4001931 Genetic variants contribute to the pathophysiology of eating disorders such as anorexia nervosa (AN) or bulimia nervosa (BN). However, the com- plex interplay between genetic and environmental factors in eating disorders is only incompletely understood. The regulation of gene expression is tightly con- trolled and well balanced in the organism by different mechanisms such as DNA methylation and histone modifications, which are known to be disturbed under several disease conditions. 1 Recent years have witnessed growing interest in epigenetic contribu- tions to psychiatric disorders 2 and evidence for epigenetic alterations has been found in different psychiatric conditions, among them schizophrenia, 2 impaired stress-response 3 and depression. 4 Recently, we have reported genomic and gene-specific DNA hypermethylation in patients with alcohol depen- dence that was associated with hyperhomo- cysteinemia. 5 Hyperhomocysteinemia is known to be present also in patients suffering from AN. 6 The aim of this study was therefore to investigate possible alterations of genomic and gene-specific DNA methylation in the peripheral blood of a well-defined sample of females with eating disorders (HEaD-study). 6 This being a pilot-study, we examined the promoter methylation of two genes previously described to be regulated by DNA methylation, the alpha synuclein gene (SNCA) and the homocysteine-induced endoplasmatic reticu- lum protein (HERP) gene. 5,7 We included 46 in-patients of a specialized hospital into the study, among them 22 women with AN (mean age 26.5710.3 years; body mass index 15.972.0 kg/m 2 ) and 24 women with BN (25.877.7 years; 22.672.6 kg/m 2 ). Measurements were controlled against 30 age-matched healthy females (22.074.8 years; 21.773.7 kg/m 2 ). All patients met Diagnostic and Statistical Manual of Mental Disorder (DSM) IV criteria for AN or BN. Diagnoses were established using the German version of the Struc- tured Clinical Interview for DSM IV diagnoses. Written informed consent was obtained from all patients after the procedures had been fully explained to them. Fasting blood samples were collected on admission in ethylenediaminetetraacetic acid- containing tubes. Homocysteine was determined by high-performance liquid chromatography using a Bio-Rad kit (BioRad, Hercules, CA, USA). Analysis of global and gene-specific DNA methylation and expression of the two genes investigated was per- formed as was recently described by us. 5,7 Between- group comparisons were performed by t-tests or one-way analysis of variance (ANOVA), followed by all pairwise comparisons according to Bonferroni using SPSS for Windows 14.0 (SPSS Inc., Chicago, IL, USA). We found a global DNA hypomethylation in patients with AN (47.7719.6%; ANOVA: F = 6.67; P = 0.002) when compared to controls (65.2710.5%; Bonferroni: P = 0.001). In addition, patients with AN showed a trend towards a lower global methylation compared to patients with BN (60.4722.3%; Bonfer- roni: P = 0.058). There was no difference between patients with BN and controls. After dividing the participants into those with normal homocysteine and those with hyperhomocysteinemia (X11.7 mmol/l), we found a significantly lower DNA methylation in the hyperhomocysteinemia group (50.8721.0% vs 62.2718.8%; t-test: T = 2.25; df = 33.4; P = 0.031). Patients suffering from both, AN and BN had significantly lower levels of SNCA mRNA (AN: DCT 2.2072.2; BN: DCT 3.2473.2; ANOVA: F = 11.7; P < 0.001) than controls (DCT 0.1271.2). Expression of HERP did not differ between groups. We found a significantly higher DNA methylation of the SNCA gene promoter in patients with AN (86.34711.4%; ANOVA: F = 3.38; P = 0.04) compared to controls (74.06723.8%; Bonferroni: P = 0.048). Patients with BN (82.83710.0%) did not differ from patients with AN and controls. No significant differences were found in the amount of DNA methylation in the HERP promoter. To our knowledge, this is the first study reporting alterations of global and gene-specific DNA methyla- tion in a sample of patients with eating disorders. We found a global DNA hypomethylation in females with AN, but not in those with BN. Elevated plasma homocysteine was associated with a reduced DNA methylation in peripheral blood cells, which is in line with several investigations in healthy probands. 8 DNA methylation occurs by transfer of a methyl Letters to the Editor 229 Molecular Psychiatry