1. Examining Stress Outcomes Among Depressed Mothers Treated with IPT Jill M. Cyranowski, Ph.D. Assistant Professor of Psychiatry and Psychology Western Psychiatric Institute and Clinic University of Pittsburgh Medical Center

2. u PMBC-related research goals u Aims of pilot study u Feasibility outcomes: recruitment, retention and compliance u Pilot study results  Acute physiological and emotional reactivity to child-focused interpersonal stressor  Examining correlates of the cortisol response to waking among depressed and never-depressed moms Overview

3. Depression And Interpersonal Life Stress  Major depression associated with perturbations in neuroendocrine and autonomic stress response  Importance of understanding depression- related HPA/SAM dysreguation within a social/interpersonal context  Evidence of interactions between depression and recent life stress or early childhood trauma

4. u If you improve interpersonal function…  alleviating interpersonal problems  increasing social support … decrease depressive symptoms u Role of stress  Interpersonal problems engender stress  Social support buffers one from the negative effects of life stress IPT as a Research Platform MOOD Interpersonal Events

5. Stress Outcomes Study (SOS): Study Goals u Use of non-invasive physiologic procedures that could be implemented in outpatient depression clinic  Salivary cortisol  Cardiovascular reactivity  Continuous EKG for Heart Period Variability (HPV) u Obtain dynamic assessment of stress system that examined stress reactivity within a social context u Examine the feasibility of study procedures  Would mothers be willing and able to participate?  Incorporation into clinic procedures

6. Stress Outcomes Study (SOS): Study Goals  Incorporate thorough psychosocial assessment  Perceived stress, early life trauma  Social support, social function  Could we incorporate a proxy evaluation of levels of expressed emotion (EE) displayed by mothers when talking about their children

7. Study Participants u Depressed mothers recruited from parent treatment trial (MH64518, Holly Swartz, PI)  Age 18-60, mother of child aged 6-18 being treated in a WPIC child psychiatric clinic  Met SCID MDD criteria, HRSD > 15  Randomly assigned to receive either IPT-MOMS or TAU (treatment as usual) u Control mothers matched on age and ethnicity u Timing of baseline (“early treatment”) assessment  Goal: within 4 weeks of entry into parent study  IPT mothers had received an average of 4 sessions prior to baseline assessment

8. Feasibility: Recruitment 36 Approached 27 Enrolled Reasons for not enrolling: ▪ 2 - Not interested ▪ 1 - Interested, but did not FU ▪ 1 - Travel too difficult ▪ 3 - Felt “overwhelmed” ▪ 1 - Work conflict 5 Withdrawn 22 Matched 12 TAU 10 IPT Reasons for withdrawal: ▪ 1 did not enter parent study ▪ 2 early d/c from parent study ▪ Time 1 assessment out of window ▪ 1 would not complete questionnaires

9. Feasibility: Retention & Compliance ControlsDepressed Time 1 Assessment 22 Time 2 Assessment 20 91% Retention rate 91% Retention rate Data available to examine AM rise in salivary cortisol 17 (77.3%) 17 (77.3%)

10. In-Clinic Stress Reactivity Task: Examining Acute Physiological and Emotional Reactivity to a Child-Focused Interpersonal Stressor

11. Give speech about “an interpersonal situation with your [son/daughter] that made you feel angry or stressed.” ■ Describe the situation ■ How did you deal with the situation? ■ How did you feel about the situation and the people involved? ■ How well do you think you handled the situation? How satisfied are you with the way it all turned out? ■ Told that speech would be video taped and that their performance would be rated at a later time Speech Stress

13. In-Clinic Reactivity Task 10 min Habituation 10 min Resting Baseline Recovery 1 (20 min) 5 min Free Speech 4 min Speech Stress Recovery 2 (20 min) Series of 2-3 BP assessments POMS assessment 2 min Speech Prep

14. Controls (N=22) IPT (N=10) TAU (N=12) Age mean (SD) 44.30 (7.41) 42.22 (7.82) 45.58 (8.53) Education mean (SD) 15.50 (2.44) 14.40 (2.95) 15.50 (2.43) BMI mean (SD) 27.59 (5.85) 28.35 (6.09) 31.34 (6.16) % Married or living with partner %86%60%58% Study Participants: Demographics

15. Controls (N=22) IPT (N=10) TAU (N=12) BDI Beck Depression mean (SD) 2.05 (1.81) 16.20* (5.47) 21.18* (8.09) MASQ GD Depression mean (SD) 15.27 (2.71) 23.60** (3.89) 31.36** (7.72) PSS Perceived Stress mean (SD) 17.77 (5.35) 33.20 (5.71) 36.73 (5.71) PSWQ Worry Questionaire mean (SD) 39.41 (10.59) 51.38* (8.52) 63.00* (13.62) Study Participants: Clinical Variables IPT vs TAU group comparison: ** p <.01, * p =.06

16. Mood Reactivity: POMS Depression Scale

17. Mood Reactivity: POMS Depression Scale

18. Mood Reactivity: POMS Depression Reactivity Scores

19. Physiological Reactivity: Diastolic Blood Pressure

20. Physiological Reactivity: Diastolic Blood Pressure

21. Physiological Reactivity: Diastolic Blood Pressure Reactivity Scores

22. Physiological Reactivity: Heart Rate

23. Physiological Reactivity: Heart Rate

24. Physiological Reactivity: Heart Rate Reactivity Scores Group effect, controlling for: marital status, smoking status, menopausal status, psychotropic med use, and cardiovascular med use, F (2,41) = 4.74, p =.01

25. Examining Correlates of the Cortisol Response to Waking Among Depressed And Never-Depressed Moms

26. Ambulatory Cortisol Assessment Protocol u Focus on feasibility of implementation  Asked to obtain samples for 2 day period  5 samples per day1 - First wake 2 - 30-mins post-wake 3 - 11:00 AM 4 - 3:00 PM 5 - 8:00 PM  Patients given pre-programmed timers, watches, and diary/instruction cards (“spit kit”)  Used MEMSCAPS for electronic verification

29. Determining Cortisol Data Integrity u Examined reliability of sample timing using MEMSCAP data and diary cards  2 waking samples – within 10 minutes  11 PM, 3:00 PM, 8:00 PM – within 60 minutes u Eliminated any subjects/samples where  Wake time > 11:00 am  Subject taking corticosteriod (Advair)  Subject indicated problem in comment section  Sample outside of temporal assessment window u Used Day 1 samples if:  Day 1 was weekday, and  First two morning samples were good  Otherwise, used Day 2 samples

30. Blunted Cortisol Response to Awakening Among Depressed Women From Stetler & Miller (2005), Journal of Abnormal Psychology

31. Ambulatory Salivary Cortisol Outcomes: Initial Assessment

32. Self-Reported Early Trauma In Depressed and Never-Depressed Women Controls (N=22) Depressed (N=22) Total (N=44) ETI – Total Severity Md52 *165 *88 ETI – Emotional Abuse Md14 *128 *48 ETI – General Trauma Md62619 ETI – Physical Abuse Md3128 ETI – Sexual Abuse Md0.50 27% of Controls scored above group Md 73% of Depressed scored above group Md

33. LES Life Events Reported in Past Year In Depressed and Never-Depressed Women Controls (N=18) Depressed (N=18) Total number of events endorsed M (SD) 3.17 (1.76) 9.50** (5.43) Cumulative positivity ratings of impact M (SD) 3.00 (3.85) 2.44 (1.95) Cumulative negativity ratings of impact M (SD) -3.00 (3.53) -17.33** (13.33) ** p <.01

34. Stability of AM Rise Indicator over 16 Week Study Period ControlsrpNrpN.683**.007 14 DepressedrpNrpN.398.159 14

35. Associations With AM Cortisol Rise: Early Life Trauma ControlsDepressed Time 1Time 2Time 1Time 2 ETI Total Severity Rho p N -.362.154 17 -.200.475 15 -.350.168 17 -.658**.008 15 ETI Emotional Abuse Rho p N -.100.703 17.007.98 15 -.270.295 17 -.537*.039 15 ETI General Trauma Rho p N -.025.923 17 -.198.478 15 -.302.238 17 -.763**.001 15

36. Associations With AM Cortisol Rise: Impact of Past Year Life Events (LES) ControlsDepressed Time 1Time 2Time 1Time 2 Cumulative Positive Impact Rho p N.591*.012 17.693**.004 15.161.536 17 -.110.697 15 Cumulative Negative Impact Rho p N -.114.664 17 -.355.194 15 -.211.416 17 -.624*.013 15

37. Depressed Group: Early Trauma (ETI) x Recent Life Events (LES) Main effect for LES, F(1,14) = 5.80, p <.05

38.  Pilot work supports the feasibility of incorporating assessment of physiologic stress reactivity and diurnal regulation within outpatient treatment trials  Importance of examining stress outcomes within an social/interpersonal context  Current social function and social stress  Early life trauma uIPT trials represent an ideal platform for examining relationship among stress, depression and interpersonal function over time  IPT conceptual model provides ideal fit  IPT provides non-pharmacologic probe to examine relationships over time Conclusions

39. Acknowledgements Holly SwartzTara Hofkens Ellen FrankHeather Spielvogle Janet AmicoKristen Frey Anna Marsland Lynda Rose Kathy Light Patty Houck Pete GianarosJohn Scott DMDPP staff Deb Stapf Grant Support: National Institute of Mental Health grants MH64144 (Cyranowski) and MH64518 (Swartz) Pittsburgh Mind-Body Center WPIC Mental Health Intervention Research Center