Major Depressive Disorder

1. Major Depressive Disorder A Depressive Disorder

2. Depressive Disorders • Disruptive Mood Dysregulation Disorder • Major Depressive Disorder • Persistent Depressive Disorder (Dysthymia) • Premenstrual Dysphoric Disorder • Substance/Medication Induced Depressive Disorder • Depressive Disorder due to another medical condition • Other specified Depressive Disorder • Unspecified Depressive Disorder

3. DepressiveDisorders • Similarities • Differences

4. History of Major Depressive Disorder in the DSM • Introduced DSM-III, 1980 • Additional Information in DSM-IV • DSM-5 changes in subtypes

5. Major Depressive Disorder DSM-IV to DSM-5 • Not included in the DSM-5 are the following Diagnostic Criteria • B. The symptoms do not meet criteria for a Mixed Episode • Coexistence within a major depressive episode of at least 3 manic symptoms (not sufficient to meet for manic episode) is now a specifier • E. The symptoms are not better accounted for by Bereavement • Allow people to grieve without a label

6. Quick Portrayal of Major Depressive Disorder • https://www.youtube.com/watch?v=twhvtzd6gXA

7. Symptoms of Depression

8. Major Depressive Disorder: DSM-5 • A. 5 (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.  Note: do not include symptoms that are clearly attributable to another medical condition • (1) Depressed mood most of the day, nearly every day • (2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day • (3) Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. • (4) Insomnia or Hypersomnia nearly every day  • (5) Psychomotor agitation or retardation nearly every day • (6) Fatigue or loss of energy nearly every day  • (7) Feelings of worthlessness or excessive or inappropriate guilt nearly every day • (8) Diminished ability to think or concentrate, or indecisiveness, nearly every day • (9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide  • B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.  • C. The episode is not attributable to the physiological effects of a substance or another medical condition • E. There has never been a manic episode or a hypomanic episode • Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical condition. The symptoms are not better accounted for by Bereavement

9. Criterion for Major Depressive Disorder A. 5 (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.  • Note: do not include symptoms that are clearly attributable to another medical condition • (1) Depressed mood most of the day, nearly every day • (2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day • (3) Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. • (4) Insomnia or Hypersomnia nearly every day  • (5) Psychomotor agitation or retardation nearly every day • (6) Fatigue or loss of energy nearly every day  • (7) Feelings of worthlessness or excessive or inappropriate guilt nearly every day • (8) Diminished ability to think or concentrate, or indecisiveness, nearly every day • (9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide 

10. Criterion for Major Depressive Disorder • B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.  • C. The episode is not attributable to the physiological effects of a substance or another medical condition • E. There has never been a manic episode or a hypomanic episode • Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical condition. The symptoms are not better accounted for by Bereavement

11. Need to Specify Severity and Course • Mild • Moderate • Severe • With psychotic features • In partial remission • In full remission • Unspecified • *Recurrent

12. …as well as Specifiers without codes • With Anxious Distress • With Mixed Features • With Melancholic Features • With Atypical Features • With Mood-Congruent Psychotic Features • With Mood-Incongruent Psychotic Features • With Catatonia • With Peripartum Onset • With Seasonal Pattern

13. Specific Notes about Children and Adolescents • Must also experience at least 4 additional symptoms drawn from a list that includes • Changes in appetite or weight, sleep, and psychomotor activity • Decreased energy • Feelings of worthlessness or guilt • Difficulty thinking, concentrating, or making decisions • Recurrent thoughts of death or suicidal ideation or suicide plans or attempts

14. Specific Notes about Children and Adolescents • What does depression in children look like? • Mood • Irritable • This pattern needs to be differentiated from a pattern of irritability when frustrated • Cranky • At School • Physical problems

15. Examples of Symptoms in Children and Adolescents • Social withdrawal or neglect of pleasurable activities • Appetite changes

16. Onset, Course, Duration • Beginning in adolescence (12-16yo)(5-19yo) • Mean age at onset 30yo • Mean age start of treatment 33.5yo • Reflects amount of time depression often goes undiagnosed or untreated • Elderly onset • At risk for downward spiral • Course is Variable • Duration Remits or Variable • Lasts 6-13 months

17. Course& Duration Specific to Youth • Course • Recurrence 1 to 2 years after remission = 20-60% • Recurrence 5 years after remission = 70% • Duration • Median Clinically referred sample = 8 months • Median Community referred sample 1-2 months

18. Prevalence in Children and Adolescence • Lifetime Prevalence of 13 to 18 year olds • The difficulty with the numbers

19. Prevalence in Children and Adolescence • Demographics (for lifetime prevalence) Sex and Age

21. FIGURE 1 Cumulative lifetime prevalence of major classes of DSM-IV disorders among adolescents (N=10,123).

22. Comorbidity and Differential Diagnosis • Highly comorbid with other psychiatric disorders • Anxiety • Dementia • Schizophrenia • Substance Abuse • Medical conditions • General • Neurological • Medications

23. Accounting for Variance in Depression • Age and Genetics (phenotype expression) • The Sample • MZM N = 106 • DZM N = 100 • MZF N = 106 • DZF N = 100 • DZOS N = 109 • - Children 8-11 years, N = 252 • - Adolescents 12-16 years, N = 244

24. Non-shared Environment Additive Genetic Shared Environment

25. Accounting for Variance in Depression • Neurobiological: HPA axis

26. Accounting for Variance in Depression • Environment • Early Life Stress • Lifetime traumas • Sexual abuse • Physical assault • Unexpected death • Abortion • Parental Loss • Sleep • Family • Parental bonding • Emotional tone of the home • Education • Substance “misuse” • Social Support

27. Accounting for Variance in Depression • Personality • Neuroticism • Self-Esteem • Early-onset anxiety disorder • Conduct Disorder • Cognition

28. A few models explaining Major Depressive Disorder • Biopsychosocial Model • Interpersonal Theory • Diathesis-Stress Model • Cognitive Vulnerability-Stress Model • Hopelessness Theory • Beck’s Theory • Maddie Marks’ Model

29. Biopsychosocial Model Depression

30. Interpersonal Theory

31. Diathesis-Stress Model Depression Diathesis Inherited predisposition Stress Loss of loved one

32. Cognitive Vulnerability-Stress Models of Depression • Hopelessness Theory • Beck’s Theory

33. Hopelessness Theory Abramson et al., 1989 Negative Event Event-Specific Inferences • Stable-global causes • Negative consequences • Negative self-characteristics Hopelessness Negative Cognitive Style Symptoms of Hopelessness Depression

34. Beck’s Theory(1967) Negative Cognitive Triad Negative Automatic Thoughts about Self, World, Future Negative Event Cognitive Distortions Negative Cognitive Style Symptoms of Depression

35. Therapy for Major Depressive Disorder

36. Neurobiological Severity Biology Genetic Risk Factors Suicide Completion Suicidal Ideation Structural Enlarged anterior Pituitary Adrenal Gland Gender Age HPA-Axis Family history of suicidal behavior Childhood Sexual Abuse Adversity Internalizing Externalizing Childhood Parental Loss Immune System Cognitive Substrates Disturbed Family Environment Sleep Childhood Self-Esteem Early-onset anxiety disorder Conduct Disorder ADHD Early Adolescence Neuroticism Educational Attainment (low) Substance Misuse Social Support (low) Late Adolescence Lifetime Traumas History of Divorce Past History of Major Depression Adulthood Stressful Life Events dependent on respondent’s own behavior Stressful Life Events independent of respondent’s own behavior Difficulties Marital Problems The Last Year

37. References Arborelius, L., Owens, M. J., Plotsky, P. M., & Nemeroff, C. B. (1999). The role of corticotropin-releasing factor in depression and anxiety disorders. The Journal of endocrinology, 160(1), 1–12. doi:10.1677/joe.0.1600001 Butler, A. C., Chapman, J. E., Forman, E. M., & Beck, A. T. (2006). The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clinical psychology review, 26(1), 17–31. doi:10.1016/j.cpr.2005.07.003 Carlson, A., & Cantwell, P. (1980). Unmasking Masked Depression in Children and Adolescents. American Jourrnal of Psychiatry, 4(137), 445–449. Cole, D. A., Peeke, L. G., Martin, J. M., Truglio, R., & Seroczynski, A. D. (1998). A Longitudinal Look at the Relation Between Depression and Anxiety in Children and Adolescents, 66(3). Dunlop, B. W., Kelley, M. E., Mletzko, T. C., Velasquez, C. M., Craighead, W. E., & Mayberg, H. S. (2012). Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder. Journal of psychiatric research, 46(3), 375–81. doi:10.1016/j.jpsychires.2011.11.003 Eley, T., & Stevenson, J. (1999). Exploring the covariation between anxiety and depression symptoms: A genetic analysis of the effects of age and sex. Journal Of Child Psychology And Psychiatry, 40(8), 1273-1282. Grant, B. F. (1995). Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults. Journal of substance abuse, 7(4), 481–97. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8838629 Gruenberg, A. M., Goldstein, R. D., & Pincus, H. A. (2005). Classification of depression: research and diagnostic criteria: DSM-IV and ICD-10. Biology of depression. From novel insights to therapeutic strategies. Hepgul, N., Cattaneo, A., Zunszain, P. a, & Pariante, C. M. (2013). Depression pathogenesis and treatment: what can we learn from blood mRNA expression? BMC medicine, 11(1), 28. doi:10.1186/1741-7015-11-28 March, J., Silva, S., Petrycki, S., Curry, J., Wells, K., Fairbank, J., … Severe, J. (2004). Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression. The Journal of the American Medical Association, 292(7), 807–820.

38. Merikangas, K. R., He, J. P., Burstein, M., Swanson, S. A., Avenevoli, S., Cui, L., Benjet, C., Georgiades, K., & Swendsen, J. (2010). Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A). Journal of the American Academy of Child & Adolescent Psychiatry, 49(10), 980-989. Mayo Clinic. (2012, February). Depression (major depression): Treatments and drugs. Retrieved from http://www.mayoclinic.com/health/depression/DS00175/DSECTION=treatments-and-drugs National Institute of Mental Health. (n.d.). Major Depressive Disorder Among Adults. Retrieved from http://www.nimh.nih.gov/statistics/1mdd_adult.shtml National Institute of Mental Health. (n.d.). Major Depressive Disorder in Children. Retrieved from http://www.nimh.nih.gov/statistics/1mdd_child.shtml Pace, T. W. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., & Heim, C. M. (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. The American journal of psychiatry, 163(9), 1630–3. doi:10.1176/appi.ajp.163.9.1630 Peeters, F., Huibers, M., Roelofs, J., van Breukelen, G., Hollon, S. D., Markowitz, J. C., … Arntz, A. (2013). The clinical effectiveness of evidence-based interventions for depression: a pragmatic trial in routine practice. Journal of affective disorders, 145(3), 349–55. doi:10.1016/j.jad.2012.08.022 Schatzberg, A. F., & Nemeroff, C. B. (Eds.). (2009). The American psychiatric publishing textbook of psychopharmacology. American Psychiatric Pub. Vreeburg, S. A., Hoogendijk, W. J., Van Pelt, J., DeRijk, R. H., Verhagen, J., Van Dyck, R., … Zitman, F. G. (2013). Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity. Archives of general psychiatry, 66(6), 617–626. Walder, D. (2009). Handbook of Depression in Children and Adolescents. Death Studies, 33(3), 297-301. Watson, N. F. (2008). The Massachusetts General Hospital Handbook of Neurology. Archives of Neurology, 65(2), 280. Zahra, S., Hossein, S., & Ali, K. V. (2012). Relationship between Opium Abuse and Severity of Depression in Type 2 Diabetic Patients. Diabetes & metabolism journal, 36(2), 157–62. doi:10.4093/dmj.2012.36.2.157