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Evidence of bidirectional associations between perceived stress and symptom activity: A prospective longitudinal investigation of perceived stress, gastrointestinal symptoms, and intestinal inflammation in inflammatory bowel disease

Kathryn A. Sexton, PhD^1,2, John R. Walker, PhD^1,2, Lesley A. Graff, PhD^1,2, Matthew T. Bernstein, BA (Hons)²,

Brooke Beatie, BA (Hons)², Norine Miller, RN¹, Michael Sargent, BSc¹, & Laura E. Targownik, MD, MSHS^1,3

The University of Manitoba ¹Inflammatory Bowel Disease Clinical and Research Centre,

and the Departments of ²Clinical Health Psychology and

3Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

SUPPLEMENTARY MATERIAL

Supplementary Table 1

Summary of hierarchical regression analysis for Month 0 variables predicting IBD symptom activity (MIBDI) at Month 6 Crohn’s Disease (n = 205) Ulcerative Colitis (n = 142)

Variables ∆R² ∆F B SE B β pr ∆R² ∆F B SE B β pr

Step 1 .12 2.85** .20 3.61***

Female Sex 0.18 0.23 .05 .06 0.21 0.25 .07 .07

Years diagnosed -0.02 0.01 -.14* -.14 -0.01 0.01 -.05 -.05 Diagnosed < 17 years old -0.07 0.37 -.01 -.01 -0.70 0.57 -.10 -.11

History IBD surgery 0.46 0.22 .15 .15 0.61 0.47 .10 .11

Use prednisone 0.54 0.47 .08 .08 -0.25 0.57 -.04 -.04

Use biologic agent 0.39 0.32 .09 .09 0.35 0.56 .05 .06

Current smoker 0.23 0.36 .04 .05 -0.01 0.69 < -.01 < -.01

Log FCAL Month 0 0.11 0.17 .04 .05 0.53 0.16 .27** .28

Perceived stress Month 0 0.04 0.01 .23** .23 0.05 0.01 .31*** .32

Step 2 .34 123.28*** .29 75.24***

Female Sex 0.06 0.18 .02 .02 0.06 0.20 .02 .03

History IBD surgery 0.39 0.18 .12* .16 0.21 0.38 .04 .05

Use prednisone 0.29 0.37 .04 .06 -0.86 0.46 -.12 -.16

Use biologic agent -0.04 0.26 -.01 -.01 -0.09 0.45 -.01 -.02

Current smoker 0.02 0.28 < .01 .01 0.14 0.55 .02 .02

Log FCAL Month 0 0.08 0.13 .03 .04 0.06 0.14 .03 .04

Perceived stress month 0 0.01 0.01 .03 .04 0.02 0.01 .12 .15

IBD symptoms Month 0 0.65 0.06 .64*** .62 0.63 0.07 .64*** .60

Note. FCAL, fecal calprotectin (μg/g stool); IBD Symptoms, Manitoba IBD Index; * p < .05; ** p < .01; *** p < .001.

Supplementary Table 2

Summary of hierarchical regression analysis for Month 0 variables predicting perceived stress at Month 6 Crohn’s Disease (n = 205) Ulcerative Colitis (n = 142)

Variables ∆R² ∆F B SE B β pr ∆R² ∆F B SE B β pr

Step 1 .11 2.62*** .11 1.84

Female Sex 1.14 1.37 .06 .06 -0.06 1.55 > -.01 > -.01

Years diagnosed -0.03 0.06 -.03 -.03 -0.06 0.07 -.08 -.08

Diagnosed < 17 years old -1.06 2.17 > -.01 > -.01 2.54 3.52 .06 .06

History IBD surgery 1.16 1.31 .06 .06 2.46 2.85 .08 .08

Use prednisone 3.26 2.79 .08 .08 -1.47 3.52 -.04 -.04

Use biologic agent 2.51 1.90 .10 .09 -0.92 3.22 -.03 -.03

Current smoker 2.23 2.11 .07 .07 4.62 4.18 .10 .10

Log FCAL Month 0 0.04 0.98 < .01 < .01 -1.39 1.04 -.12 -.12

IBD symptoms Month 0 1.38 0.42 .23** .22 1.76 0.52 .31** .28

Step 2 .41 162.63*** .44 126.69***

Female Sex 0.48 1.01 .02 .03 0.47 1.11 .03 .04

History IBD surgery 2.60 0.97 .14** .19 1.12 2.04 .04 .05

Use prednisone 1.92 2.06 .05 .07 -0.25 2.52 -.01 -.01

Use biologic agent 0.92 1.41 .04 .05 -0.07 2.31 < -.01 < -.01

Current smoker 2.06 1.56 .07 .09 0.52 3.01 .01 .02

Log FCAL Month 0 0.47 0.72 .03 .05 0.13 0.76 .01 .02.

IBD symptoms Month 0 0.12 0.33 .02 .03 0.29 0.40 .05 .07

Perceived stress Month 0 0.74 0.06 .69*** .68 0.69 0.06 .72*** .70

Note. FCAL, fecal calprotectin (μg/g stool); IBD Symptoms, Manitoba IBD Index; * p < .05; ** p < .01; *** p < .001.

Supplementary Table 3

Summary of hierarchical regression analysis for Month 0 variables predicting intestinal inflammation (log FCAL) at Month 6 Crohn’s Disease (n = 208) Ulcerative Colitis (n = 145)

Variables ∆R² ∆F B SE B β pr ∆R² ∆F B SE B β pr

Step 1 .05 1.03 .06 1.03

Female Sex > -0.01 0.11 > -.01 > -.01 -0.13 0.12 -.09 -.09

Years diagnosed -0.01 0.01 -.14 -.13 -0.01 0.01 -.08 -.08

Diagnosed < 17 years old 0.06 0.17 .03 .03 -0.27 0.28 -.08 -.08

History IBD surgery -0.10 0.10 -.08 -.07 0.04 0.23 .02 .02

Use prednisone -0.17 0.22 -.06 -.06 0.19 0.28 .06 .06

Use biologic agent 0.02 0.15 .01 .01 0.17 0.26 .06 .06

Current smoker 0.10 0.16 .04 .04 -0.11 0.34 -.03 -.03

Perceived stress Month 0 -0.01 0.01 -.11 -.10 > -0.01 0.01 -.03 -.03 IBD symptoms Month 0 < 0.01 0.03 -.01 < .01 0.07 0.04 .16 .15

Step 2 .28 81.12*** .15 25.34***

Female Sex -0.01 0.09 -.01 -.01 -0.11 0.11 -.08 -.08

History IBD surgery -0.06 0.08 -.05 -.05 0.09 0.21 .04 .05

Use prednisone -0.27 0.18 -.09 -.10 0.24 0.26 .07 .08

Use biologic agent 0.09 0.12 .04 .05 0.17 0.24 .06 .06

Current smoker 0.02 0.14 .01 .10 -0.08 0.31 -.02 -.02

Perceived stress month 0 -0.01 0.01 -.09 -.11 < 0.01 0.01 .05 .05 IBD Symptoms at Month 0 ^I >-0.01 0.03 -.01 -.01 -0.01 0.04 -.03 -.03

Log FCAL Month 0 0.58 0.06 .53*** .54 0.39 0.08 .43*** .40

Note. FCAL, fecal calprotectin (μg/g stool); IBD Symptoms, Manitoba IBD Index; *** p < .001.