The aim of the studies in this genetic epidemiological thesis was to investigate candidate genes that play a role in the etiology of depression and to obtain new insights about biological pathways that may be involved in this disorder. The introduction of the thesis presents a review of all genetic studies on major depressive disorder (MDD), addressing 393 polymorphisms in 102 genes. Meta-analyses of the twenty-two polymorphisms that had been investigated in at least three studies showed statistically significant associations for six polymorphisms in the following genes: apolipoprotein E (APOE), guanine nucleotidebinding protein (GNB3), methylene-tetrahydrofolate reductase (MTHFR), serotonin transporter (SLC6A4), dopamine transporter (SLC6A3) and the dopamine receptor D4 (DRD4). Next, the thesis describes two candidate gene studies on the association between depression and the angiotensin I converting enzyme insertion/deletion (ACE I/D) and the angiotensino! gen (AGT) M235T polymorphisms. In a large-scale population-based and family-based study, men carrying the AGT M235T TT genotype had more symptoms of depression, but there was no evidence for an association between the ACE gene and depression. Finally, the thesis reports three studies on the co-morbidity of symptoms of depression with socioeconomic status, cardiovascular risk factors and body composition. These studies showed evidence for a common genetic etiology between symptoms of depression with both socioeconomic status and lipid parameters. This thesis shows that genetic research on depression is still in an early stage. More research is necessary both to confirm reported genetic associations and to identify new susceptibility genes. Interesting areas of gene discovery may be found in the overlapping etiological pathways of socioeconomic status and lipid parameters with depression.

Additional Metadata
Keywords depression, depressive, epidemiology, genetic, meta-analysis, polymorphism
Promotor C.M. van Duijn (Cock) , B.A. Oostra (Ben)
Publisher Erasmus University Rotterdam
Sponsor The work presented in this thesis was conducted at the Genetic Epidemiology Unit, Departments of Epidemiology & Biostatistics and Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. The Rotterdam Study is supported Prof.dr. D.I. Boomsma Prof.dr. J. Del-Favero Prof.dr. F.C. Verhulst Dr. A.C.J.W. Janssens (co-promotor) by the Erasmus University Medical Center and the Erasmus University Rotterdam, the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organisation for Health Reseach and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), the Municipality of Rotterdam, and the Center for Medical Systems Biology (CMSB). The ERF Study is supported by the Center for Medical Systems Biology (CMSB), the Netherlands Organization for Scientific Research (NWO), the Dutch Kidney Foundation, the Dutch Heart Foundation, the Dutch Brain Foundation, Internationale Stichting Alzheimer Onderzoek (ISAO), and the Dutch Diabetes Foundation. Special thanks to the general practitioners and pharmacists in the Ommord district for their contributions to the Rotterdam Study and to the general practitioners in the ERF region for their contributions to the ERF Study. The printing of this thesis was supported by the Department of Epidemiology & Biostatistics, the Department of Clinical Genetics, the Department of Public Health, the Erasmus University Rotterdam, AstraZeneca, Biogen International BV, J.E. Jurriaanse Stichting, Lundbeck BV, Servier, and Wyeth.
ISBN 978-909022-993-5
Persistent URL hdl.handle.net/1765/12896
Citation
López León, S.. (2008, May 14). Genetic Determinants of Depression. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/12896