Studying the Psychophysiology of Social Dysfunction in Depression Cardiac Vagal Function In Depressed and Nondepressed Women Jill M. Cyranowski, Holly A. Swartz, Tara L. Hofkens, and Peter J. Gianaros Western Psychiatric Institute and Clinic University of Pittsburgh Medical School

PresenterCompanyProductResearchOther: J.M. CyranowskiNIMHX Pittsburgh Foundation X Disclosures

Study Collaborators Tara L. Hofkens Peter J. Gianaros Kristin Salomon Holly A. Swartz Janet Amico Ellen Frank, DMDPP clinic Grant Support MH64144, MH30915 Clinical Neuroscience Research Center (RR ), Pittsburgh Mind-Body Center (HL076852/076858)

u Myocardium of the heart is dually innervated by sympathetic and parasympathetic branches of the autonomic nervous system (ANS)  Parasympathetic inputs provide inhibitory control of heart rate via direct innervation of the heart by the vagus nerve u The “Vagal Brake”  Vagal activation: slows HR to favor energy conservation / parasympathetic dominance during times of rest or perceived safety  Vagal withdrawal: rapid shift to sympathetic dominance during time of threat/stress Cardiac Vagal Function

u Indirect indicators of cardiac vagal control – measured via continuous EKG, spectral analyses  Vagal effects on HR occur rapidly (in milliseconds)  Changes in HR that occur in high frequency range of HR variability ( Hz) used to index vagal tone (commonly referred to as high-frequency HPV or respiratory sinus arrhythmia - RSA) u Depression associated with impaired cardiac vagal function (indexed via diminished RSA)  Rottenberg (2007) meta-analysis: Obtained small-to-medium (d=.332) effect size of depression  Though multiple methodological issues Cardiac Vagal Function

 Collateral branches of the vagus also terminate on soft palate, pharynx, larynx, facial muscles - involved in emotional expression and social communication

u Polyvagal Theory (Porges, 2007) vagal pathways evolved in mammals to allow for social engagement & affiliation via flexible (vagal) modulation of sympathetic fight-or-flight responses, and facilitation of emotional expression & social communication u Diminished vagal function (⇩ RSA) associated with: (1) Cardiac-hemodynamic dysregulation - CVD risk (2) Emotional dysregulation - depression & anxiety (3) Social dysfunction – unmarried, social isolation Depression and Vagal Dysfunction

Methodological Issues  Thus, diminished vagal function may represent a biological mechanism related to common patterns of cardiac-hemodynamic as well as emotional and social dysfunction in depression  Methodological issues in extant literature  Inclusion of subjects on antidepressants  Lack of control for respiratory rate  No control for trauma history  Most designs assess resting state vagal control or vagal withdraw in response to acute stress  But little on social factors expected to trigger vagal activation

Study Sample  Females aged  15 depressed, 15 age/race matched controls  Medical and Psychiatric Screening  Medically healthy, normal cycling  Antidepressant-free for at least 4 weeks  Psychiatric screening with SCID, HRSD DepressedNon-Depressed Mean age (SD)31.77 (6.65)27.89 (4.58) % Caucasian (n)86.6% (13) BMI, mean (SD)24.08 (2.81)24.69 (4.34) BDI, mean (SD) *19.36 (7.19)2.4 (2.87) BAI, mean (SD) *17.07 (10.40)3.07 (4.38)

Study Design  Laboratory Study  Testing sessions scheduled at 2pm  Instrumented with 3-lead EKG and upper abdominal strain gauge to assess respiratory rate u 2 Laboratory Tasks (order counterbalanced)  Stress task ⇨ vagal withdrawal  Relationship-focused imagery ⇨ vagal activation 25 m Habituation 20 minute Resting Baseline 10 min TASK # 1 30 minute Resting Recovery 20 minute Resting Baseline 30 minute Resting Recovery 20 min Rest

Measures  Respiratory Sinus Arrhythmia (RSA)  EKG signal sampled continuously at 1000 Hz  Spectral-power values in the Hz bandwidth integrated for each 1-min epoch  Respiration Rate  Breaths per minute via strain gauge  Trauma History Questionnaire (Green, 1995)  Lifetime history of crime, general disaster or trauma, sexual/physical assault experiences DepressedNon-Depressed Low (0-1 event)7 (46.7%)9 (60%) High (>2 events)8 (53.3%)6 (40%)

Analyses u Repeated measures ANOVAs for RSA outcomes over the course of each study task  2 (Group) x 2 (Trauma History) x 2 (Task Order)  Period (Baseline, Task, Recovery 1, Recovery 2) u Models controlling for respiratory rate  Methods advocated by Grossman et al (2007)  W ithin-subject linear regression models – calculated standardized residual scores representing the variance in RSA for each 1- min epoch that could not be attributed to within- subject fluctuations in respiration rate for the same 1-min epoch

Results: Impact of Lab Tasks on RSA Speech Stress Task F(3,66) = 4.36, p=.02 Relationship Imagery Task F(3,66) = 3.79, p=.02

Non-adjusted RSA: Period [F(3,66)=3.79, p=.02]; Group [F(1,22)=5.54, p=.028] Relationship Imagery Results

Non-adjusted RSA: Period [F(3,66)=3.79, p=.02]; Group [F(1,22)=5.54, p=.028]

Stress Task Results Models with non-adjusted RSA. Period [F(3,66)=4.36,p=.02], Group x Trauma History [F(1,22)=9.61, p=.05]

Stress Task Results Models with non-adjusted RSA. Period [F(3,66)=4.36,p=.02], Group x Trauma History [F(1,22)=9.61, p=.05]

Stress Task Results Models with adjusted RSA. Period [F(3, 60)=3.79, p =.04], Trauma History [F(1,20)=4.05, p=.058], Trauma History X Task Order [F(1,20)=6.46, p=.02]

Study Limitations  Small, selected sample of depressed women  Generalizability of study findings  High level of anxiety comorbidity in the depressed group (no anxiety among controls)  Particularly comorbid GAD (73%)  However, findings held after removing 2 subjects with PTSD  Trauma history assessment - simple event count  Did not assess timing or severity of trauma

Study Strengths / Future Directions  Select, well-characterized study group  Medically healthy, antidepressant free  Well-controlled study design  Assessment of respiratory rate  Large effect sizes (partial eta squared >.14)  Inclusion of tasks designed to elicit vagal activation and vagal withdrawal  Conclusions – Directions for future research  Importance of social context in RSA assessment  Potential impact of trauma history in evaluating of stress-induced vagal withdrawal among depressed samples

Vagal Function, Depression and IPT  IPT treatment targets relevant to vagal function  Depression, anxiety and social function  Prospective research designs needed  IPT could be used as nonpharmacologic probe  Will within-subject, IPT-related improvements in depression / anxiety, ⇩ in social distress, or ⇧ in perceived social support impact vagal function?  Improvement in vagal function - potential biological mechanism of change in effective IPT treatment?