Mood Disorders II (Chapter 7) March 10, 2014 PSYC 2340: Abnormal Psychology Brett Deacon, Ph.D.

1. Mood Disorders II(Chapter 7)March 10, 2014PSYC 2340: Abnormal PsychologyBrett Deacon, Ph.D.

2. Announcements • Exam #2 handed back today • Midterm grades turned in this week

3. From Last Class • Major depressive episode • Major depressive disorder • Manic episode • Bipolar disorder • Psychosocial influences • Negative life events • Negative cognitions • Behavioral withdrawal

4. Familial and Genetic Influences • Family studies • Rate is high in relatives of probands • Twin studies • Concordance rates high in identical twins • Severe cases have a stronger genetic contribution • Genetic contribution to depression is approximately 40% (less for men); somewhat higher for bipolar disorder

5. Caspi et al. (2003) study • 847 New Zealanders followed from birth to 26 • Examined association between stressful life events and genetics and development of depression • Life stress: index of 14 events • 3 genoptypes of 5-HTT gene: • 2 short alleles (17%) – considered worst • 2 long alleles (31%) • 1 of each (51%)

6. Caspi et al. (2003) study • Found strong association between life events and episodes of depression • No significant association between genotype and depression • Stress x genotype interaction. For those with > 4 stressful life events between ages of 21 and 26, depression occurred in: • 43% of those with 2 short alleles • 33% of those with 1 of each • 17% of those with 2 long alleles

7. Caspi et al. (2003) study

8. Caspi et al. (2003) study

9. Caspi et al. (2003) study • But… • Findings not consistently replicated by other researchers • Of interest, 5-HTT genotype was unrelated to the development of depression in the absence of negative life events • “Normal” vs. “abnormal” depression

10. Genetic Influences • Cytochrome P450 polymorphisms • Slow, rapid, & ultrarapid metabolizers of SSRI medications • Obvious clinical implications! • Efficacy • Adverse effects • Popular to test for this at Mayo Clinic (cost = $1803.04)

11. Genetic Influences • In 2007, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group published a report on the scientific status of the cytochrome P450 test in the scientific journal Genetics in Medicine. The report states the following: “…CYP450 genotypes are not consistently associated with the patient outcomes of interest, including clinical response to SSRI treatment or adverse events as a result of treatment. No evidence was available showing that the results of CYP450 testing influenced SSRI choice or dose and improved patient outcomes, or was useful in medical, personal, or public health decision-making. In the absence of evidence supporting clinical utility, it is not known if potential benefits from CYP450 testing will outweigh potential harms. Potential harms may include increased cost without impact on clinical decision making or improvement in patient outcomes, less effective treatment with SSRI drugs, or inappropriate use of genotype information in the management of other drugs metabolized by CYP450 enzymes. • The article concluded: “The EGAPP Working Group found insufficient evidence to support a recommendation for or against use of CYP450 testing in adults beginning SSRI treatment for non-psychotic depression. In the absence of supporting evidence, and with consideration of other contextual issues, EGAPP discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed.” The full report can be accessed here: http://www.egappreviews.org/docs/EGAPPWG-CYP450Rec.pdf.

12. Neurobiological Influences • Neurotransmitters • The “chemical imbalance theory” of depression (aka, “low serotonin theory”) • Twin: the “dopamine hypothesis of schizophrenia”

13. Neurobiological Influences • Primary evidence for chemical imbalance theory is based on reasoning backward from benefits of antidepressant medications. • Logic of the argument is as follows: • (a) Medications that raise serotonin levels in the brain are effective in reducing depressive symptoms. • (b) Therefore, depression is caused by low levels of serotonin in the brain.

14. Neurobiological Influences • Caution against a simple chemical imbalance explanation of depression: • Pills that raise serotonin levels alleviate depression • Pills that lower serotonin levels alleviate depression • Pills that have no effect on serotonin levels alleviate depression • Sugar pills alleviate depression • Note also that psychotherapy changes the brain

15. Neurobiological Influences • Caution against a simple chemical imbalance explanation of depression: • Serotonin levels rise and fall with changes in social status among primates • Depleting serotonin levels does not consistently produce depression • Massive increases in serotonin do not consistently alleviate depression • No one knows what a “chemical balance” looks like, let alone an “imbalance”

16. Chemical Imbalance in Depression: Selected Quotes • “Research indicates that depressive illnesses are disorders of the brain……important neurotransmitters – chemicals that brain cells use to communicate – appear to be out of balance.” - NIMH • “Depression is a treatable medical illness involving an imbalance of brain chemicals called neurotransmitters and neuropeptides.” -DBSA • “When you have depression, chemicals in your brain called neurotransmitters are out of balance.”-WebMD • “If you have depression, you may have a serotonin imbalance.” -Mayo Clinic • “While the cause is unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Prescription Zoloft works to correct this imbalance.”-Pfizer ad

17. Chemical Imbalance Explanation • Mayo Clinic: How antidepressants relieve depression • http://www.mayoclinic.com/health/antidepressants/MM00660

18. Popularity of Chemical Imbalance Explanation • Our research on clients in an intensive outpatient clinic for anxiety disorders (N = 353) • 69.7% (n = 246) had been told by a healthcare provider that their anxiety symptoms were caused by a chemical imbalance in the brain • Among 15 causal explanations, only stress was more common (75.9%)

19. Chemical Imbalance in Depression: Selected Quotes • “Chemical imbalance is sort of last-century thinking. It's much more complicated than that. It's really an outmoded way of thinking.” –Joseph Coyle • “In truth, the ‘chemical imbalance’ notion was always a kind of urban legend – never a theory seriously propounded by well-informed psychiatrists.”-Ronald Pies • "I don't think there's any convincing body of data that anybody has ever found that depression is associated to a significant extent with a loss of serotonin.” -Alan Frazer • “What we are missing is an understanding of the biology of the disorders and what is really going wrong.” -Thomas Insel • Irish FDA equivalent action against GlaxoSmithKline

20. Understanding the Popularity of the Chemical Imbalance Theory • National Public Radio story: “When It Comes To Depression, Serotonin Isn't The Whole Story” • http://www.npr.org/blogs/health/2012/01/23/145525853/when-it-comes-to-depression-serotonin-isnt-the-whole-story

21. Chemical Imbalance Explanation • How does receiving a chemical imbalance explanation affect individuals with mental health problems? • Two studies from my research lab…

22. Deacon & Baird (2009) Study Overview • Participants: 90 undergraduate students enrolled in abnormal psychology class • Thought experiment methodology • Disease/chemical imbalance model vs. biopsychosocial model Deacon, B. J., & Baird, G. (2009). The chemical imbalance explanation of depression: Reducing blame at what cost? Journal of Clinical and Social Psychology, 28, 415-435.

23. Disease Model Description • Disease condition • “Depression is a common medical illness that is no different from any other disease. It is caused by a chemical imbalance in the brain involving the neurotransmitter serotonin. It is not the result of a personal weakness or character flaw and is not something that can be overcome through willpower or by pulling yourself together.”

24. Biopsychosocial Model Description • Biopsychosocial condition • “Depression is a common mental disorder. There are a number of reasons why a person might become depressed, including having a family history of depression, stressful life experiences like the death of a loved one, and having low self-esteem and a pessimistic attitude. It is probably a combination of biological, environmental, and psychological factors that cause depression in most individuals.”

25. Results: Self-Stigma (Blame) ** ** p <.001

26. Results: Prognosis and Control ** *p < .05; ** p <.001

27. Results: Treatment Expectancies ** ** p <.001

28. Kemp, Lickel, & Deacon Study Overview • Participants: 69 undergraduate students • True experiment methodology • Randomly assigned to chemical imbalance (n = 35) vs. no chemical imbalance (n = 34) feedback conditions

29. Kemp, Lickel, & Deacon Study Overview • Procedures: • Described purpose of study • Rapid Depression Test • 10 minute waiting period • Self-report questionnaires

30. Chemical Imbalance Condition Test Result CONCLUSION: 99.97% probability of serotonin deficiency.

31. Control Condition Test Result CONCLUSION: No deficiency detected

32. Study Findings • Compared to the control group, the chemical imbalance group: • Did not report less self-blame • Reported themselves as less likely to eventually recover and that their depression would be more chronic • Reported less ability to manage depressive symptoms themselves • Described antidepressant medication as more credible and effective than psychotherapy

33. Research Summary • Consistent relationship between endorsement of biological cause of one’s symptoms and prognostic pessimism. Found in: • Depression • Generalized anxiety disorder • Eating disorders • Obesity

34. Chemical Imbalance Explanation • National Public Radio story: “When It Comes To Depression, Serotonin Isn't The Whole Story” • So why are so many people still talking about low serotonin causing depression? Frazer says it's probably because it has had, and continues to have, important cultural uses. For one, he says, by initially framing the problem as a deficiency — something that needed to be returned to normal — patients felt more comfortable taking a drug. "If there was this biological reason for them being depressed, some deficiency that the drug was correcting," Frazer says, then taking a drug was OK. "They had a chemical imbalance and the drug was correcting that imbalance." • Chemical imbalance explanation is viewed as critical to convince people to take antidepressants

35. Clinical Implications of Chemical Imbalance Explanation • Many depressed individuals do not perceive antidepressants to be necessary and/or are concerned about their adverse effects • This is especially true for those who are younger, believe their symptoms will not last a long time, attribute their symptoms to psychosocial factors, and do not view their depression as a biologically-based brain disorder (Aikens, Nease, Klinkman, 2008)

36. Clinical Implications of Chemical Imbalance Explanation • How can doctors get such individuals to take their medication? • “Perceived need for antidepressant medication was associated with older age, greater symptom severity, the perception that one’s symptoms are caused by biochemical factors, and the expectation that one’s symptoms will persist. These associations might guide clinicians who are aiming to improve depression outcomes. If non-adhering patients seem to underestimate the severity or persistence of their depressive symptoms, physicians might wish to highlight the historical impact of the symptoms and discuss the typical chronicity of depression. It may be similarly beneficial to help patients develop realistic expectations about whether their symptoms will remit without treatment.Addressing these factors explicitly might enable patients to make a more fully informed choice about whether to use antidepressants.” (p. 27; Aikens, Nease, Klinkman, 2008)