Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit–hyperactivity disorder and bipolar disorder

• Published in: Journal of affective disorders 2012-05, Vol.138 (3), p.479-484
• Main Authors: Marín-Méndez, Juan Jesús, Patiño-García, Ana, Segura, Victor, Ortuño, Felipe, Gálvez, Mª. Dolores, Soutullo, César A
• Format: Article
• Language: English
• Subjects: ADHD; Adolescent; Adult and adolescent clinical studies; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit disorders. Hyperactivity; Attention deficit hyperactivity disorder; Biological and medical sciences; Bipolar affective disorder; Bipolar disorder; Bipolar Disorder - genetics; Bipolar disorders; Brain; Child; Child clinical studies; Female; Gene Expression; Genes; Genome-Wide Association Study; Humans; Intramolecular Oxidoreductases - genetics; Lipocalins - genetics; Male; Medical sciences; Mood disorders; Phenotype; Phenotypes; Prostaglandin D2 synthase; Psychiatric disorders; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Young Adult
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2012.01.040

Abstract Background As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP. Materials and methods We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used. Results Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p = 0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p > 0.05). Conclusions The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders. Limitations Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.