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Genetics of Depression

Genetics of Depression. สมาชิกกลุ่มที่ 2 นาย บุญเสริม พรจันทึก 545030038-1 นาย เทียนชัย สร้อยรักษ์ 545030066-6 นางสาววรางคณา แดนสีแก้ว 545030069-0 นางสาวกานต์สิรีเกศ เลิศสรรสิริ 545030065-8. major depressive disorder ( mdd ). Common and moderately heritable

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Genetics of Depression

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  1. Genetics of Depression สมาชิกกลุ่มที่ 2 นายบุญเสริม พรจันทึก 545030038-1 นายเทียนชัย สร้อยรักษ์ 545030066-6 นางสาววรางคณา แดนสีแก้ว 545030069-0 นางสาวกานต์สิรีเกศ เลิศสรรสิริ 545030065-8

  2. major depressive disorder (mdd) • Common and moderately heritable • Overlaping genetic susceptibilities • Suicidal behavior • Stress vulnerability • Hypothalamic-pituitary axis • Bipolar disorder (BD)

  3. genetic epidemiology MDD • The risk in women twice • Heritability based on twin • environmental risk factors • include childhood abuse • Neglect • life stress

  4. genetic epidemiology Anxiety Disorders and Neuroticism • personality • characterized by dysphoria • anxiety • tension • emotional reactivity

  5. association studies of candidate genes • Monoaminergic Candidate Genes and Gene-Environment Interactions • Serotonin • Tridimensional Personality Questionnaire • Single nucleotide polymorphisms

  6. evidence of genetic etiology • Serotonin transporter gene-link polymorphic region (5-HTTLPR) - Ass.withneuroticism,depression & anxiety personality trait. (Lescs, et al.,1996) - long allele ass.with good response to Tx. - short allele ass.with poor response to Tx. (Lee, et al.,2004; Arais, et al.,2003)

  7. Association Studies of Candidate Genes • 5-HTTLPR, Stress and Depression • Short alleles • antidepressant

  8. 5-HTTLPR Neuroticism Precipitating Factors Unipolar Depression Disorders Anxiety Disorders Lesch KP. Gene-enviroment interaction and the genetic of depression. Rev Psy Neuroscience.1996;29(3):174-184

  9. stressors Loss control of his stress response

  10. How MDD develops Early postnatal mother- Infant experiences Altered metabolism Stress response S+S: Decreased appetite, Restlessness Decreased libido Immune suppression Increased REM sleep Fatigue Myalgia Imprinted into Hippocampus (memory+retrieval learning, dreaming) Hypothalamus ANS Corticotrophin-releasing hormone (CRH) Stressor Pituitary gland (anterior) (-) ACTH cortisol Adrenal gland (cortex)

  11. genetic linkage studies

  12. future directions • The positional cloning strategy • Whole-genome association • Mechanisms of depression susceptibility • Next generation

  13. Mechanisms of depression susceptibility • depression susceptibility • perhaps including cortisol hypersecretion • dysregulation of sleep • structural changes in the hippocampus and subgenual prefrontal cortex • electroencephalographic • psychophysiological • newer neurobiological hypotheses

  14. Next generation • whole-genome linkage • dense LD mapping of all genes in a candidate region • network of interacting genes detected by an unbiased method • whole-network gene expression studies • proteomic methods • convergent evidence from two or more systematic strategies

  15. conclusion although it will be a challenging problem touncover the genetic mechanisms underlying susceptibility todepression and related traits, it appears likely that the challengecan be met using technology that is either feasible now or that should be available quite soon.

  16. Thank You For Your Attention

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