title: Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders.
abstract: It is well established that stress is a risk factor for onset of mood disorders. Emerging evidence suggests that genetic vulnerability may also moderate individual responsiveness to stress. The most compelling evidence regards the polymorphism within the promoter region of the serotonin transporter gene (SERTPR), which has been reported to moderate the risk for depression, in conjunction with life stressors. In the present paper we analysed SERTPR in the onset of mood disorders, along with adverse life events, and other candidate genes: the serotonin receptor 1A (5-HT1A), the dopamine receptor D4 (DRD4) and the catechol-O-methyltransferase (COMT). The sample was composed of 686 Italian subjects, affected by major depression and bipolar disorder. Patients were asked to report about life stressors within the year preceding onset of their first mood-disorder episode and genotyped. A 'case-only' design was employed to investigate the interaction between genes and stressors. COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). In our retrospective study SERTPR is hypothesized to lead to the onset of major depression via its influence on reaction to adversities, particularly in females. Moreover, COMT was risk factor for onset of both major depression and bipolar disorder, in conjunction with adversities.
authors.affiliation: Institute of Psychiatry, University of Bologna, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mandelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Elena
authors.initials: E
authors.lastname: Marino
authors.forename: Adele
authors.initials: A
authors.lastname: Pirovano
authors.forename: Raffaella
authors.initials: R
authors.lastname: Calati
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications*; D011795:Surveys and Questionnaires
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase