Studying the Psychophysiologyof Social Dysfunction in Depression

Cardiac Vagal FunctionIn Depressed and Nondepressed Women

Jill M. Cyranowski, Holly A. Swartz, Tara L. Hofkens, and Peter J. Gianaros

Western Psychiatric Institute and ClinicUniversity of Pittsburgh Medical School

Presenter Company Product Research Other:

J.M. Cyranowski NIMH X

Pittsburgh Foundation

X

Disclosures

Study Collaborators

Tara L. HofkensPeter J. GianarosKristin SalomonHolly A. Swartz

Janet AmicoEllen Frank, DMDPP clinic

Grant SupportMH64144, MH30915Clinical Neuroscience Research Center (RR0000056), Pittsburgh Mind-Body Center (HL076852/076858)

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

Cardiac Vagal Function

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

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

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 toacute 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

Depressed Non-Depressed

Mean age (SD) 31.77 (6.65) 27.89 (4.58)

% Caucasian (n) 86.6% (13) 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 2 Laboratory Tasks (order counterbalanced) Stress task ⇨ vagal withdrawal Relationship-focused imagery ⇨ vagal activation 25 m

Habituation

20 minute

RestingBaseline

10 min

TASK# 1

30 minute

RestingRecovery

20 minute

RestingBaseline

30 minute

RestingRecovery

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

Depressed Non-Depressed

Low (0-1 event) 7 (46.7%) 9 (60%)

High (>2 events) 8 (53.3%) 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 scoresrepresenting the variance in RSA for each 1-min epoch that could not be attributed to within-subject fluctuations in respiration rate for thesame 1-min epoch

RSA During Relationship Imagery

6.4

6.5

6.6

6.7

6.8

6.9

GI Baseline GI Task GI Recovery 1 GI Recovery 2

RSA During Stress Session

6.1

6.2

6.3

6.4

6.5

6.6

6.7

Baseline Speech prep Recovery 1 Recovery 2

Results: Impact of Lab Tasks on RSA

Speech StressTaskF(3,66) = 4.36,p=.02

Relationship Imagery TaskF(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

RSA During Relationship Imagery Condition

5.8

6

6.2

6.4

6.6

6.8

7

7.2

7.4

Baseline Imagery Recovery 1 Recovery 2

Task Period

Me

an

RS

A

Non-DepressedDepressed

Relationship Imagery Results

Mean RSA During Relationship Imagery Condition

5.8

6

6.2

6.4

6.6

6.8

7

7.2

Non-Depressed Depressed

Depression Group

Mea

n R

SA

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

6.1

6.2

6.3

6.4

6.5

6.6

6.7

6.8

Baseline Speech Prep Recovery 1 Recovery 2

Task Period

Mea

n R

SA

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

5.6

5.8

6

6.2

6.4

6.6

6.8

7

7.2

Non-Depressed DepressedDepression Group

Mea

n R

SA

Low Trauma

High Trauma

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

RSA During 1-Hour Speech Stress Condition

-3

-2

-1

0

1

2

3

Low Trauma High TraumaDepression Group

Re

sp

ira

tio

n-A

dju

ste

d R

SA

Stress Task 1st

Stress Task 2nd

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?