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
Disclosures
Presenter
Company
Product
Research
Other:
J.M. Cyranowski
NIMH
X
Pittsburgh
Foundation
X
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
(RR0000056), Pittsburgh Mind-Body Center
(HL076852/076858)
Cardiac Vagal Function
 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
 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
 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 (0.15-0.50 Hz) used to index vagal
tone (commonly referred to as high-frequency HPV
or respiratory sinus arrhythmia - RSA)
 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
 Collateral branches of the vagus also terminate on
soft palate, pharynx, larynx, facial muscles - involved in
emotional expression and social communication
Depression and Vagal Dysfunction
 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
 Diminished vagal function (⇩ RSA) associated
with:
(1) Cardiac-hemodynamic dysregulation - CVD risk
(2) Emotional dysregulation - depression & anxiety
(3) Social dysfunction – unmarried, social isolation
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 20-40
 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
Mean age (SD)
Depressed
31.77 (6.65)
Non-Depressed
27.89 (4.58)
% Caucasian (n)
BMI, mean (SD)
86.6% (13)
24.08 (2.81)
86.6% (13)
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
 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
20 minute
30 minute
Resting
Recovery
Resting
Baseline
Resting
Recovery
20 min
Rest
Measures
 Respiratory Sinus Arrhythmia (RSA)
 EKG signal sampled continuously at 1000 Hz
 Spectral-power values in the 0.15-0.50 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
Low (0-1 event)
High (>2 events)
Depressed
7 (46.7%)
8 (53.3%)
Non-Depressed
9 (60%)
6 (40%)
Analyses
 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)
 Models controlling for respiratory rate
 Methods advocated by Grossman et al (2007)
 Within-subject linear regression models –
calculated standardized residual scores
representing the variance in RSA for each 1min epoch that could not be attributed to withinsubject fluctuations in respiration rate for the
same 1-min epoch
Results: Impact of Lab Tasks on RSA
RSA During Stress Session
Speech Stress
Task
F(3,66) = 4.36,
p=.02
6.7
6.6
6.5
6.4
6.3
6.2
6.1
Baseline
Speech prep
Recovery 1
Recovery 2
RSA During Relationship Imagery
Relationship
Imagery Task
F(3,66) = 3.79,
p=.02
6.9
6.8
6.7
6.6
6.5
6.4
GI Baseline
GI Task
GI Recovery 1
GI Recovery 2
Relationship Imagery Results
RSA During Relationship Imagery Condition
7.4
Non-Depressed
Depressed
7.2
Mean RSA
7
6.8
6.6
6.4
6.2
6
5.8
Baseline
Imagery
Recovery 1
Recovery 2
Task Period
Non-adjusted RSA: Period [F(3,66)=3.79, p=.02];
Group [F(1,22)=5.54, p=.028]
Relationship Imagery Results
Mean RSA During Relationship Imagery Condition
7.2
Mean RSA
7
6.8
6.6
6.4
6.2
6
5.8
Depressed
Non-Depressed
Depression Group
Non-adjusted RSA: Period [F(3,66)=3.79, p=.02];
Group [F(1,22)=5.54, p=.028]
Stress Task Results
RSA During the Speech Stress Condition
6.8
6.7
Mean RSA
6.6
6.5
6.4
6.3
6.2
6.1
6
Baseline
Speech Prep
Recovery 1
Recovery 2
Task Period
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
Mean RSA During the 1-Hour Speech Stress Condition
7.2
Low Trauma
7
High Trauma
Mean RSA
6.8
6.6
6.4
6.2
6
5.8
5.6
Non-Depressed
Depressed
Depression Group
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
3
RSA During 1-Hour Speech Stress Condition
Respiration-Adjusted RSA
Stress Task 1st
2
Stress Task 2nd
1
0
-1
-2
-3
Low Trauma
Depression Group
High Trauma
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?