Gerry Giesbrecht, PhD, R Psych Department of Paediatrics, University of Calgary Alberta Children’s Hospital Research Institute

Overview of Today’s Talk

Why exposure timing is an important topic in developmental science.

How change in maternal stress

physiology during pregnancy could explain time effects.

Cortisol remains a potent stress signal throughout pregnancy.

The Effects of Exposures Depend on Timing

Source: Class et al. (2011). Psychosomatic Medicine, 73, 234-241.

Birth outcomes as a function of GA and stress exposure

Source: Davis & Sandman (2010). Child Development, 81, 131-148.

Cognitive development as a function of GA and cortisol

Conclusion

Early exposure is worse than later exposure.

Period of hypo-responsivity

What Causes Timing Effects?

Changes in Biological Vulnerability

Fetal Development

Changes in Maternal Stress Physiology

Attenuation of Perceived Stress

Source: Glynn et al. (2004) Journal of Psychosomatic Research, 56, 47-52.

Attenuation of Heart Rate Response to Stress

Source: Entringer et al. (2010). Stress, 13, 258-268.

Note: No cortisol response in either group.

Lack of Cortisol Response to Cold Stress

Source: Kammerer et al. (2002) BMC Pregnancy and Childbirth, 2:8.

GA = 37 weeks

Lack of Cortisol Response to CRH in Late Gestation

Source: Schulte et al. (1990) Clinical Endocrinology, 33, 99-106

39 weeks GA

4-5 weeks post-partum

Summary

HPA axis resists acute changes Could dose reduction explain the timing effects?

Giesbrecht et al., (2012). Psychoneuroendocrinology, 37, 270-279

Does the HPA axis become insensitive to psychological stimulation?

Evidence of cortisol reactivity in late gestation

Source: De Weerth et al. (2007) Acta Obstetricia et Gynecologica, 86, 1181-1192.

33 weeks GA

3.4 nmol/l

3.2 nmol/l

Evidence of cortisol reactivity in late gestation

Source: Schulte et al. (1990) Clinical Endocrinology, 33, 99-106

39 weeks GA

4-5 weeks post-partum

Overview of Assessments: Pregnancy, Mood, and Cortisol Study

Study Protocol

0.2

0.22

0.24

0.26

0.28

0.3

0.32

0.34

0.36

0.38

2

2.2

2.4

2.6

2.8

3

3.2

3.4

3.6

3.8

4

1st 2nd 3rd

Cor

tisol

ug/

dL

Psyc

holg

ical

Dis

tres

s

Trimester

Distress

Cortisol

Average Cortisol and Distress Trajectories over Pregnancy

Association Model Interpretation Momentary (level 1) Effects Estimate SE p WAKING Levels -1.64 .026 <.001 Waking level = 0.19 µg/dL CAR .32 .049 <.001 38% increase TIME -.12 .006 <.001 11.3% decrease/hour TIME2 .002 .0007 .001 0.2% increase/hour2

PSYCHOLOGICAL DISTRESS .024 .008 .006 Maximum effect = 31% increase Gestation Age (level 2) Effects For Waking Levels For CAR For Time For Time2 For Psychological Distress

Cortisol and Psychological Distress Covary over Time

Association Model Moderator Model Momentary (level 1) Effects Estimate SE p Estimate SE p WAKING Levels -1.64 .026 <.001 -1.62 .025 <.001 CAR .32 .049 <.001 .32 .047 <.001 TIME -.12 .006 <.001 -.12 .005 <.001 TIME2 .002 .0007 .001 .002 .0007 .004 PSYCHOLOGICAL DISTRESS .024 .008 .006 .024 .006 <.001 Gestation Age (level 2) Effects For Waking Levels .027 .002 <.001 For CAR -.006 .005 .17 For Time .001 .0005 .02 For Time2 -.0002 .00007 .02 For Psychological Distress .0009 .0006 .13

Covariation between Cortisol and Psychological Distress is not Attenuated by Advancing Gestation

Conclusion

HPA axis remains responsive to psychological stimulation.

Attenuation of maternal stress response is not a plausible explanation for the effects of exposure timing.

Acknowledgments

Collaborators Bonnie Kaplan Tavis Campbell Nicole Letourneau & the APrON study Team

Trainees & Assistants Codie Rouleau Diego Padilla Ontanon Tiffany Haig Julia Poole Amy Hampson