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Developments in Depression

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  1. Developments in Depression Timothy Dellenbaugh, MD Asssociate Professor of Psychiatry Psychiatry Residency Director UMKC

  2. Topics • Genetics • Natural Hx and risk factors • Service Delivery • Suicide Risk • Treatment

  3. Pretest

  4. Genetic Linkage for depression has been reported for which chromosomes • 8 • 11 • 13 • 15 • 17 • 22 • All of the above

  5. Individuals with which polymorphism of the HTR2A gene (13) were NOT responsive to the protective aspects of nurturing mothering • T/T • T/C • C/C

  6. When there were No reported adversities, the risk of adolescent depression was the same between low birth weight and normal weight females • True • False

  7. Individuals with late life onset depression had greater impairment than early onset • True • False

  8. The decrease in antidepressant utilization after the FDA Advisory was offset by increased use of other medications • True • False

  9. After the FDA advisory, patients started on antidepressants received closer follow-up as recommended • True • False

  10. When patients had equal mood reactivity to sad mood provocation, their relapse risk was lower if they had been treated with CBT instead of antidepressants • True • False

  11. High density negative-ion therapy was just as effective as light therapy for seasonal affective disorder • True • False

  12. Genetics

  13. Genetics of Recurrent Early-Onset Major Depression • Am J Psychiatry 2007; 164:248–258 • DNA markers were studied in 656 families with two or more cases • (onset before age 31 in probands and age 41 in other relatives) • Genomewide suggestive evidence for linkage was observed on chromosome 15q25-q26 • In the secondary analysis, suggestive linkage results were observed on chromosome 17p12 (28.0 cM,excess sharing in male-male and male-female pairs) • and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs). • Conclusions: These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major depression and related disorders. • Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.

  14. Genetic Variation in Suicideand Major Depression • Arch Gen Psychiatry. 2006;63:35-48 • Chromosome 22 • Spermine is stored in synaptic vesicles and released by depolarization neurotransmitters • Impacts effects of lithium • Impacts serotonin reuptake • SSAT (spermine/spermidine N1-acetyltransferase), may play a role in the predisposition to suicide and major depression

  15. Genetic Markers of Suicidal Ideation Emerging DuringCitalopram Treatment of Major Depression • Am J Psychiatry 2007; 164:1530–1538 • DNA samples from 1,915 participants were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genes • genes GRIA3 (chromosome X) • And GRIK2 (Chromosome 6) • Encode ionotropic glutamate receptors

  16. Association of GRIK4 With Outcome of AntidepressantTreatment in the STAR*D Cohort • Am J Psychiatry 2007; 164:1181–1188 • homozygote carriers of both the GRIK4 (11) • and HTR2A (13) genes were 23% less likely to experience nonresponse to treatment relative to participants who did not carry any of these marker alleles

  17. Serotonin Receptor 2A Gene and the Influenceof Childhood Maternal Nurturance on AdulthoodDepressive Symptoms • Arch Gen Psychiatry. 2007;64:356-360 • Individuals carrying the T/T or T/C genotype of the T102C polymorphism of the HTR2A gene (13) were responsive to the protective aspects of nurturing mothering, so that in the presence of high maternal nurturance, they expressed low levels of depressive symptoms, while this was not true with the carriers of the C/C genotype.

  18. Natural Hx and risk factors

  19. Prediction From Low Birth Weightto Female Adolescent Depression • Arch Gen Psychiatry. 2007;64:338-344 • 1420 participants • 49% were female • prevalence of depression among adolescent girls with LBW was 38.1% compared with • 8.4% among adolescent girls with normal birth weight • No difference with no adversities

  20. Arch Gen Psychiatry. 2007;64:338-344

  21. Association of Different Adverse Life EventsWith Distinct Patterns of Depressive Symptoms • Am J Psychiatry 2007; 164:1521–1529 • 4,856 individuals • (53% female) • who experienced depressive symptoms in the previous year were assessed

  22. Am J Psychiatry 2007; 164:1521–1529

  23. Families at High and Low Risk for Depression • Arch Gen Psychiatry. 2005;62:29-36 • Longitudinal, retrospective cohort, family study. • 161 grandchildren and their parents and grandparents • major findings of this 3-generation study are • the moderating effects of grandparental depression on the association between parental depression and grandchild diagnoses • the importance of impairment in depression criteria • the finding that anxiety disorders are an early sign of psychopathology in children from depressed families

  24. Effect of Age at Onset on the Courseof Major Depressive DisorderAm J Psychiatry 2007; 164:1539–1546 • the older age-at-onset groups, especially the late-adult-onset group, had the mildest, least pervasive, least dysfunctional, and less recurrent forms • Earlier ages of onset were associated with substantial functional impairment (e.g., poor social and occupational function, poor quality of life) • and greater illness burden (more current general medical and psychiatric comorbidity, • a more negative view of life and the self, • more lifetime episodes of depression, • more severe depressive episodes, • more lifetime suicide attempts, • and greater suicidal ideation)

  25. Effect of Age at Onset on the Courseof Major Depressive DisorderAm J Psychiatry 2007; 164:1539–1546

  26. Prevalence and Distribution of Major DepressiveDisorder in African Americans, Caribbean Blacks,and Non-Hispanic Whites • Arch Gen Psychiatry. 2007;64:305-315 • 3570 African Americans, • 1621 Caribbean blacks, and • 891 non-Hispanic whites • aged 18 years and older (N=6082)

  27. Arch Gen Psychiatry. 2007;64:305-315 • Lifetime MDD prevalence estimates were highest for whites (17.9%), followed by Caribbean blacks (12.9%) and African Americans (10.4%) • 12-month MDD estimates across groups were similar • The chronicity of MDD was higher for both black groups (56.5% for African Americans and 56.0% for Caribbean blacks) than for whites (38.6%). • Fewer than half of the African Americans (45.0%) and fewer than a quarter (24.3%) of the Caribbean blacks who met the criteria received any form of MDD therapy. • In addition, relative to whites, both black groups were more likely to rate their MDD as severe or very severe and more disabling.

  28. A Longitudinal Study of the Use of Mental Health Servicesby Persons With Serious Mental Illness: Do Spanish-SpeakingLatinos Differ From English-Speaking Latinos and Caucasians? Am J Psychiatry 2007; 164:1173–1180

  29. A Qualitative Analysis of the Perception of Stigma Among Latinos Receiving Antidepressants Psychiatric Services 58:1591–1594, 2007 • Antidepressant use was seen as implying more severe illness, weakness or failure to cope with problems, and being under the effects of a drug • Stigma was a prominent concern among Latinos receiving antidepressants, and • stigma often affected adherence. • culture is likely to play an important role in the communication of stigma and its associated complications

  30. Does Stigma Keep Poor Young Immigrantand U.S.-Born Black and Latina WomenFrom Seeking Mental Health Care? Psychiatric Services 58:1547–1554, 2007

  31. Changes in Health Care Use and CostsAfter a Break in Medicaid CoverageAmong Persons With Depression Psychiatric Services 58:49–54, 2007 • Utilization of emergency and inpatient services and Medicaid expenditures significantly increased for beneficiaries with depression when they returned to Medicaid after experiencing a temporary loss in coverage, • especially for beneficiaries with a documented disability. • significant increases in the utilization of inpatient and emergency services are experienced by enrollees when returning to Medicaid after an interruption in coverage • suggesting that some individuals may be reenrolled in Medicaid by providers when presenting for acute care services. • The causes for the observed increased utilization of acute care services are not known.

  32. The Costs and Benefits of Enhanced Depression Care to Employers Arch Gen Psychiatry. 2006;63:1345-1353 • Hypothetical cohort of 40-year-old workers. • Our societal perspective analyses suggest that a program of enhanced depression care for workers, consisting of a 1-time workplace depression screen plus telephonic care management for depressed employees, yields gains in quality-adjusted life expectancy at a cost in the range seen for commonly accepted medical interventions covered by employer-sponsored health plans • These results suggest that, like primary care depression interventions, enhanced depression care for workers appears to be a good investment of society’s resources.

  33. FDA advisory Effects on treatment

  34. Decline in Treatment of Pediatric Depression After FDAAdvisory on Risk of Suicidality With SSRIs Am J Psychiatry 2007; 164:884–891

  35. Decline in Treatment of Pediatric Depression After FDAAdvisory on Risk of Suicidality With SSRIs Am J Psychiatry 2007; 164:884–891 • Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions in new diagnoses. • Among patients with depression, the proportion receiving no antidepressant increased to three times the rate predicted by the preadvisory trend • SSRI prescription fills were 58% lower than predicted by the trend. • There was no evidence of a significant increase in use of treatment alternatives (psychotherapy, atypical antipsychotics, and anxiolytics).

  36. Spillover Effects on Treatment of Adult Depressionin Primary Care After FDA Advisory on Risk ofPediatric Suicidality With SSRIsAm J Psychiatry 2007; 164:1198–1205

  37. Spillover Effects on Treatment of Adult Depressionin Primary Care After FDA Advisory on Risk ofPediatric Suicidality With SSRIsAm J Psychiatry 2007; 164:1198–1205

  38. Spillover Effects on Treatment of Adult Depressionin Primary Care After FDA Advisory on Risk ofPediatric Suicidality With SSRIsAm J Psychiatry 2007; 164:1198–1205 • The October 2003 advisory was the first in a series of risk communications • a second public health advisory followed in October 2004 • February 2005 black box warning and language for a patient medication guide were implemented which was nonspecific and stated that youths and adults may be at risk • May 2007- the FDA extended the black box warning to include young adults, ages 19–24

  39. Frequency of Provider Contact After FDA Advisory on Risk of Pediatric Suicidality With SSRIsAm J Psychiatry Morrato et al.; AiA:1–9 • The medication guide provides information for parents, including a frequency schedule suggesting that pediatric patients should have a total of seven visits with their physician during the first 3 months of antidepressant drug therapy—once a week for the first month, every 2 weeks for the second month, and a visit at 3 months. • Between the initial advisory and the black box warning, the FDA also issued a public health advisory about use of antidepressants in adults and strengthened warnings about the need to monitor all patients for worsening of depression, especially early in treatment and after dosage changes

  40. Frequency of Provider Contact After FDA Advisory on Risk of Pediatric Suicidality With SSRIsAm J Psychiatry Morrato et al.; AiA:1–9

  41. Frequency of Provider Contact After FDA Advisory on Risk of Pediatric Suicidality With SSRIsAm J Psychiatry Morrato et al.; AiA:1–9 • Less than 5% of all patients met FDA contact recommendations before the advisory • and the rate did not change after the advisory.

  42. Intervention Studies Drugs and More

  43. Early Onset of Selective SerotoninReuptake Inhibitor Antidepressant ActionArch Gen Psychiatry. 2006;63:1217-1223 • Randomized controlled trials of SSRIs vs placebo for the treatment of unipolar depression in adults that reported outcomes for at least 2 time points in the first 4 weeks of treatment • Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week • A secondary analysis indicated an increased chance of achieving a 50% reduction in Hamilton Depression Rating Scale scores by 1 week (relative risk, 1.64; 95% confidence interval, 1.2-2.25) with SSRI treatment compared with placebo. • Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use, and the improvement continues at a decreasing rate for at least 6 weeks.

  44. Combined Treatment With Sertralineand Liothyronine in Major DepressionArch Gen Psychiatry. 2007;64:679-688 • Response = 70% sertraline-liothyronine • 50% sertraline-placebo (P=.02; odds ratio, 2.93; 95% confidence interval, 1.23-7.35); • remission rates were 58% with sertraline-liothyronine • and 38% with sertraline-placebo • (P=.02; odds ratio, 2.69; 95% confidence interval, 1.16-6.49). • Baseline T3 values were lower in patients treated with sertralineliothyronine who had remissions than in those without remissions (t48=3.36; P.002). • Among patients treated with sertraline-liothyronine, remission was associated with a significant decrease in serum thyrotropin values (F1,73=4.00; P.05). • There were no significant effects of liothyronine supplementation on frequency of adverse effects.

  45. A Comparison of Lithium and T3 AugmentationFollowing Two Failed Medication Treatmentsfor Depression: A STAR*D ReportAm J Psychiatry 2006; 163:1519–1530 • 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial • Remission rates with lithium and T3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. 16% vs.25%

  46. Cognitive Reactivity to Sad Mood Provocationand the Prediction of Depressive RelapseArch Gen Psychiatry. 2006;63:749-755 • In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. • In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months • Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. • Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months.

  47. Controlled Trial of Naturalistic Dawn Simulation andNegative Air Ionization for Seasonal Affective DisorderAm J Psychiatry 2006; 163:2126–2133

  48. Controlled Trial of Naturalistic Dawn Simulation andNegative Air Ionization for Seasonal Affective DisorderAm J Psychiatry 2006; 163:2126–2133 • Posttreatment improvement results were • bright light, 57.1%; • dawn simulation, 49.5%; • dawn pulse, 42.7%; • highdensity ions, 47.9%; • and low-density ions, 22.7% (significantly lower). • Contrary to the authors’ hypothesis, analysis of variance failed to find superiority of dawn simulation to the dawn pulse or bright light. • However, the dawn pulse led to a pattern of residual or exacerbated depressive symptoms similar to those seen in low-density ion nonresponders

  49. Posttest

  50. Genetic Linkage for depression has been reported for which chromosomes • 8 • 11 • 13 • 15 • 17 • 22 • All of the above