Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-25T17:10:23.548Z Has data issue: false hasContentIssue false

Chapter 6 - Genetic and genomic studies of major depressive disorder

Published online by Cambridge University Press:  19 October 2021

By
Roy H. Perlis
Edited by
Chad E. Beyer  and
Stephen M. Stahl
Chad E. Beyer
Affiliation:
University of Colorado School of Medicine
Stephen M. Stahl
Affiliation:
University of California, San Diego
Get access

Summary

Family studies indicate that major depressive disorder runs in families, although family members’ risk for other psychiatric disorders may also be increased. Twin and adoption studies suggest that about one-third of the liability for MDD is inherited. Studies investigating individual candidate genes have failed to implicate any single gene in MDD risk. Emerging evidence from genome-wide association studies may identify novel risk genes, although any individual genetic variation appears likely to have only modest effect. Whether focusing on clinical subtypes of MDD, or relying on imaging or other biomarkers rather than clinical features, will expedite the process of gene discovery remains to be determined.

Type
Chapter
Information
Next Generation Antidepressants
Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders
 , pp. 90 - 101
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Weissman, M M, Merikangas, K R, John, K, Wickramaratne, P, Prusoff, B A, Kidd, K K. Family genetic studies of psychiatric disorders. Developing technologies. Arch Gen Psychiatry. Nov 1986;43(11):1104–16.CrossRefGoogle ScholarPubMed
Sullivan, P F, Neale, M C, Kendler, K S. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. Oct 2000;157(10):1552–62.CrossRefGoogle ScholarPubMed
Weissman, M M, Wickramaratne, P, Adams, P B, et al. The relationship between panic disorder and major depression. A new family study. Arch Gen Psychiatry. Oct 1993;50(10):767–80.Google Scholar
Smeraldi, E, Negri, F, Heimbuch, R C, Kidd, K K. Familial patterns and possible modes of inheritance of primary affective disorders. J Affect Disord. Jun 1981;3(2):173–82.CrossRefGoogle ScholarPubMed
Neale, M C, Cardon, L R. Methodology for the Study of Twins and Families. Dordrecht, the Netherlands: Kluwer; 1992.Google Scholar
Kessler, R C, Chiu, W T, Demler, O, Merikangas, K R, Walters, E E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. Jun 2005;62(6):617–27.Google Scholar
Wender, P H, Kety, S S, Rosenthal, D, Schulsinger, F, Ortmann, J, Lunde, I. Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry. Oct 1986;43(10):923–29.Google Scholar
Cadoret, R J, O’Gorman, T W, Heywood, E, Troughton, E. Genetic and environmental factors in major depression. J Affect Disord. Sep 1985;9(2):155–64.Google Scholar
International HandMap Consortium. The International HapMap Project. Nature. Dec 18 2003;426(6968):789–96.Google Scholar
Caspi, A, Sugden, K, Moffitt, T E, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. Jul 18 2003;301(5631):386–89.CrossRefGoogle ScholarPubMed
Risch, N, Herrell, R, Lehner, T, et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA. Jun 17 2009;301(23):2462–71.CrossRefGoogle ScholarPubMed
Liu, Z, Zhu, F, Wang, G, et al. Association of corticotropin-releasing hormone receptor1 gene SNP and haplotype with major depression. Neurosci Lett. Sep 1 2006;404(3):358–62.CrossRefGoogle ScholarPubMed
Bradley, R G, Binder, E B, Epstein, M P, et al. Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch Gen Psychiatry. Feb 2008;65(2):190–200.CrossRefGoogle ScholarPubMed
Utge, S, Soronen, P, Partonen, T, et al. A population-based association study of candidate genes for depression and sleep disturbance. Am J Med Genet B Neuropsychiatr Genet. Jun 22 2009 [Epub ahead of print].Google Scholar
Cichon, S, Craddock, N, Daly, M, et al. Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am J Psychiatry. May 2009;166(5):540–56.Google ScholarPubMed
Purcell, S M, Wray, N R, Stone, J L, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature Aug 2009; 460(7256):748–52.Google ScholarPubMed
Ferreira, M A, O’Donovan, M C, Meng, Y A, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. Sep 2008;40(9):1056–58.CrossRefGoogle ScholarPubMed
Sullivan, P F, de Geus, E J, Willemsen, G, et al. Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry. Apr 2009;14(4):359–75.Google Scholar
Zeggini, E, Scott, L J, Saxena, R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. May 2008;40(5):638–45.Google Scholar
St Clair, D, Blackwood, D, Muir, W, et al. Association within a family of a balanced autosomal translocation with major mental illness. Lancet. Jul 7 1990;336(8706):13–16.Google Scholar
Schosser, A, Gaysina, D, Cohen-Woods, S, et al. Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies. Mol Psychiatry. Mar 3 2009 [Epub ahead of print].Google Scholar
Papadimitriou, G N, Souery, D, Lipp, O, et al. In search of anticipation in unipolar affective disorder. Eur Neuropsychopharmacol. Oct 2005;15(5):511–16.Google Scholar
Perlis, R H, Smoller, J W, Mysore, J, et al. Prevalence of incompletely penetrant Huntington’s Disease alleles among individuals with major depressive disorder. Am J Psychiatry, in press.Google Scholar
Goldstein, D B. Common genetic variation and human traits. N Engl J Med. Apr 23 2009;360(17):1696–98.CrossRefGoogle ScholarPubMed
Licinio, J, Dong, C, Wong, M L. Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. Arch Gen Psychiatry. May 2009;66(5):488–97.CrossRefGoogle ScholarPubMed
Tsankova, N, Renthal, W, Kumar, A, Nestler, E J. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci. May 2007;8(5):355–67.CrossRefGoogle ScholarPubMed
Philibert, R A, Sandhu, H, Hollenbeck, N, Gunter, T, Adams, W, Madan, A. The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet. Jul 5 2008;147B(5):543–49.Google Scholar
Poulter, M O, Du, L, Weaver, I C, et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry. Oct 15 2008;64(8):645–52.Google Scholar
Kendler, K S, Gardner, C O, Prescott, C A. Clinical characteristics of major depression that predict risk of depression in relatives. Arch Gen Psychiatry. Apr 1999;56(4):322–27.Google Scholar
Gottesman, I I, Gould, T D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. Apr 2003;160(4):636–45.Google Scholar
Greenwood, T A, Braff, D L, Light, G A, et al. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry. Nov 2007;64(11):1242–50.Google Scholar
Costa, P T, Jr., McCrae, R R. Influence of extraversion and neuroticism on subjective well-being: happy and unhappy people. J Pers Soc Psychol. Apr 1980;38(4):668–78.Google Scholar
Ormel, J, Oldehinkel, A J, Vollebergh, W. Vulnerability before, during, and after a major depressive episode: a 3-wave population-based study. Arch Gen Psychiatry. Oct 2004;61(10):990–96.Google Scholar
Kendler, K S, Gatz, M, Gardner, C O, Pedersen, N L. Personality and major depression: a Swedish longitudinal, population-based twin study. Arch Gen Psychiatry. Oct 2006;63(10):1113–20.Google Scholar
Lake, R I, Eaves, L J, Maes, H H, Heath, A C, Martin, N G. Further evidence against the environmental transmission of individual differences in neuroticism from a collaborative study of 45,850 twins and relatives on two continents. Behav Genet. May 2000;30(3):223–33.CrossRefGoogle Scholar
van den Oord, E J, Kuo, P H, Hartmann, A M, et al. Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism. Arch Gen Psychiatry. Sep 2008;65(9):1062–71.Google Scholar
Litwack, E D, Babey, R, Buser, R, Gesemann, M, O’Leary, D D. Identification and characterization of two novel brain-derived immunoglobulin superfamily members with a unique structural organization. Mol Cell Neurosci. Feb 2004;25(2):263–74.Google Scholar
Shifman, S, Bhomra, A, Smiley, S, et al. A whole genome association study of neuroticism using DNA pooling. Mol Psychiatry. Mar 2008;13(3):302–12.Google Scholar
Hariri, A R, Mattay, V S, Tessitore, A, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science. Jul 19 2002;297(5580):400–03.CrossRefGoogle ScholarPubMed
Munafo, M R, Brown, S M, Hariri, A R. Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry. May 1 2008;63(9):852–57.Google Scholar
Perlis, R H, Holt, D J, Smoller, J W, et al. Association of a polymorphism near CREB1 with differential aversion processing in the insula of healthy participants. Arch Gen Psychiatry. Aug 2008;65(8):882–92.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×