1. GENETICS OF DEPRESSION PSYC 301 Jade Vega

2. OVERVIEW Depression Depression Categories of Depression Categories of Depression Depression & The Brain Depression & The Brain Causes of Depression Causes of Depression Population Genetics Population Genetics Twin, Adoption, and Family Studies Twin, Adoption, and Family Studies Molecular Genetics Molecular Genetics Association Studies and Candidate Genes Association Studies and Candidate Genes Epigenetics Epigenetics Conclusion Conclusion

3. DEPRESSION Depression affects an estimated 1 in 10 adults in the United States (CDC, 2011). It is the most common cause of disability worldwide (WHO, 2013). Although symptoms vary greatly, they commonly include: persistent sad, anxious, pessimistic, or "empty" feelings; irritability and restlessness; fatigue and decreased overall energy; difficulty concentrating; insomnia, excessive sleeping, or other sleep disturbances; And thoughts of suicide and/or suicide attempts (NIMH) A graphical representation showing percentages of adults who meet the criteria for depression, by state. Courtesy of the Centers for Disease Control and Prevention.

4. CATEGORIES OF DEPRESSION Major Depressive Disorder Major Depressive Disorder Symptoms must be present nearly every day for a diagnosis Dysthymia- “Persistent Depressive Disorder” depressed mood for the most of the day, more days than not, for at least two years symptoms may not be severe enough to disable a person, but that they "can prevent normal functioning or feeling well" (National Institute of Mental Health) Minor Depression Seasonal Affective Disorder (SAD) Postpartum Depression Substance and Alcohol-Induced Depression Psychotic Depression Bipolar Disorder is sometimes referred to as “manic depression”

5. DEPRESSION AND THE BRAIN Depressive disorders are widely considered to be disorders of the brain Structural imaging has revealed (in individuals with severe and persistent major depression): decreased volume of the hippocampus, basal ganglia, orbitofrontal cortex, and subgenual prefrontal cortex (Rigucci, Serafini, Pompili, Kotzalidis, & Tatarelli, 2010) Most current research is focused on searching for abnormalities in circuit level connectivity, rather than brain regions. PET scans of the brain may reveal what type of treatment individuals with major depression will respond to PET scan of a depressed individual's brain compared to a scan of a non-depressed person. The scan of the depressed individual's brain shows decreased activity in comparison. Courtesy of the Mayo Clinic.

6. CAUSES OF DEPRESSION Researchers tend to agree that depression is caused by a combination of many factors- genetic, environmental, and psychological. Factors which increase risk of developing depression: Being related to somebody who has depression Being a woman Environmental factors such as traumatic childhood experiences, stressful life events, having a serious illness, having a history of depression, possessing certain personality traits- such as pessimism and low self- esteem, and abusing alcohol or drugs (Mayo Clinic, 2012).

7. POPULATION GENETICS Heritability is defined as the "amount of variation for a trait that can be attributed to genetic influences" (Elder & Mosack, 2011, p. 192). The estimated heritability for major depression is 38 percent. It is believed that major depression has a higher rate of heritability than less severe and later- onset forms do (Elder & Mosack, 2011). Much of what we know about the heritability of major depression has come as a result of studying population genetics. The population genetics of depression are most commonly researched through: twin, adoption, and other family-based studies.

8. TWIN, ADOPTION, AND FAMILY STUDIES Twin studies Twin studies Popular in depression studies because they reveal information about environmental and genetic factors Popular in depression studies because they reveal information about environmental and genetic factors Have shown that there is equal heritability of major depression in men and women (Kendler & Prescott, 2000) Adoption Studies Adoption Studies allow researchers to estimate the impact of heredity over the influence of environmental factors Family Studies have revealed that if an individual who a parent or sibling with major depression, they are two or even three times more likely to develop depression than the average person (Stanford School of Medicine) Environmental factors are still important, in addition to hereditary predisposition

9. MOLECULAR GENETICS Genetics can be studied at the population level or at the molecular level Ways to study molecular genetics include: Linkage studies Genetic association studies (at the gene or genome level) Studies at the molecular level have shown that there are several candidate genes that may cause depression

10. ASSOCIATION STUDIES AND CANDIDATE GENES Linkage and Association Studies Linkage and Association Studies In linkage studies, related individuals are observed. To date, however, few studies have found compelling evidence for linkage. In this case, linkage refers to "genome-wide level significance“ (Hettema, 2010, p. 317). Association Studies Association Studies Case-control comparisons of unrelated individuals Family-based transmission tests Researchers can test specific genes or specific markers within those genes for their contribution to traits and illnesses Many such studies to date have focused on "the 44-base pair insert/deletion polymorphism (5-HTTLPR) occurring in the promoter region of the serotonin transporter gene" (p. 320) Over 32 other genes have been researched and hypothesized to be involved with causing depression, in conjunction with environmental factors.

11. EPIGENETICS Epigenetics refers to the study of "heritable changes in gene expression that occur without a change in DNA sequence" (Wolffe & Matzke, 1999, p. 481) Epigenetic profiles, like DNA sequences, are inherited Epigenetic changes, however, are reversible Changes to epigenetics are induced by environmental factors One study has found evidence that microRNAs regulate gene expression. This means that microRNAs may contribute to depression (He, Zhou, Xi, Cui, Luo, Song, Nie, Wang & Ying, 2012) Epigenetics may be important in depression development, although the science and associated technology is still relatively new, and further research is essential.

12. FUTURE RESEARCH Although researchers have come a long way in understanding that the causes of depression are complex and vary amongst individuals, there is still plenty of research needed. Future research will attempt to: Replicate the findings of studies that have found potentially causative genes Narrow down the genes to determine which are most crucial in disorder development, as well as explain why there are so many possible contributors Use wider-scale genome-wide association studies to detect genetic abnormalities in larger groups in less time Research the potential role of epigenetics in depression predisposition

13. CONCLUSION Discovering the role of genetics in depression has shown us that depression is not something individuals can just "get over"- it is a serious mental disorder which affects every aspect of patients' lives Understanding the complex ways in which genes interact with environment to determine disorder expression is crucial to understanding how to best treat the disorder, thus minimizing suffering.

14. RESOURCES TO HELP UNDERSTAND DEPRESSION Video: “I had a black dog, his name was depression” – World Health Organization Video: “I had a black dog, his name was depression” – World Health Organization http://www.youtube.com/watch?v=XiCrniLQGYc http://www.youtube.com/watch?v=XiCrniLQGYc http://www.youtube.com/watch?v=XiCrniLQGYc Suggested Reading, Courtesy of PBS: Suggested Reading, Courtesy of PBS: http://www.pbs.org/wgbh/takeonestep/depression/resources-reading.html http://www.pbs.org/wgbh/takeonestep/depression/resources-reading.html http://www.pbs.org/wgbh/takeonestep/depression/resources-reading.html National Alliance on Mental Illness National Alliance on Mental Illness http://www.nami.org/ http://www.nami.org/ http://www.nami.org/ American Psychological Association American Psychological Association http://www.apa.org/topics/depress/index.aspx http://www.apa.org/topics/depress/index.aspx http://www.apa.org/topics/depress/index.aspx

15. REFERENCES Centers for Disease Control and Prevention. (2011). An estimated 1 in 10 u.s. adults report depression. Retrieved from http://www.cdc.gov/features/dsdepression/ http://www.cdc.gov/features/dsdepression/ Elder, B., & Mosack, V. (2011). Genetics of depression: An overview of the current science. Issues in Mental Health Nursing, 32(4), 192- 202. He, Y., Zhou, Y., Xi, Q., Cui, H., Luo, T., Song, H., Nie, X., & Wang, L. (2012). Genetic variations in microrna processing genes are associated with susceptibility in depression. DNA & Cell Biology, 31(9), 1499-1506. Hettema, J. (2010). Genetics of depression. Focus, 8, 316-322. Kendler, K., & Prescott, C. (1999). A population-based twin study of lifetime major depression in men and women. Archives of General Psychiatry, 56(1), 39-44. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9892254http://www.ncbi.nlm.nih.gov/pubmed/9892254 Mayo Clinic. (2012). Depression. Retrieved from http://www.mayoclinic.com/health/depression/DS00175http://www.mayoclinic.com/health/depression/DS00175 National Institute of Mental Health. Depression. Retrieved from http://www.nimh.nih.gov/health/topics/depression/index.shtmlhttp://www.nimh.nih.gov/health/topics/depression/index.shtml Rigucci, S., Serafini, G., Pompili, M., Kotzalidis, G., & Tatarelli, R. (2010). Anatomical and functional correlates in major depressive disorder: The contribution of neuroimaging studies. World Journal of Biological Psychiatry, 11(2), 165-180. Wolffe, A., & Matzke, M. (1999). Epigenetics: regulation through repression. Science, 286(5439), 481-486. World Health Organization. (2012). Depression. Retrieved from http://www.who.int/mediacentre/factsheets/fs369/en/index.htmlhttp://www.who.int/mediacentre/factsheets/fs369/en/index.html