Cognitive Behavioral Therapy for Antenatal Depression in a Pilot Randomized Controlled Trial and Effects on Neurobiological, Behavioral and Cognitive Outcomes in Offspring 3-7 Years Postpartum: A Perspective Article on Study Findings, Limitations and Future Aims

Laura S Bleker; Jeannette Milgrom; Alexandra Sexton-Oates; Donna Parker; Tessa J Roseboom; Alan W Gemmill; Christopher J Holt; Richard Saffery; Alan Connelly; Huibert Burger; Susanne R de Rooij

doi:10.3389/fpsyt.2020.00034

Cognitive Behavioral Therapy for Antenatal Depression in a Pilot Randomized Controlled Trial and Effects on Neurobiological, Behavioral and Cognitive Outcomes in Offspring 3-7 Years Postpartum: A Perspective Article on Study Findings, Limitations and Future Aims

Front Psychiatry. 2020 Feb 13:11:34. doi: 10.3389/fpsyt.2020.00034. eCollection 2020.

Authors

Laura S Bleker^{1

2}, Jeannette Milgrom^{3

4}, Alexandra Sexton-Oates⁵, Donna Parker⁶, Tessa J Roseboom^{1

2}, Alan W Gemmill³, Christopher J Holt³, Richard Saffery⁵, Alan Connelly⁶, Huibert Burger^{7

8}, Susanne R de Rooij²

Affiliations

¹ Academic Medical Centre, Department of Obstetrics and Gynecology, Amsterdam UMC, Amsterdam, Netherlands.
² Academic Medical Centre, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands.
³ Parent-Infant Research Institute, Austin Health, Melbourne, VIC, Australia.
⁴ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia.
⁵ Murdoch Children's Research Institute-Cancer and Disease Epigenetics, Royal Children's Hospital, Melbourne, VIC, Australia.
⁶ Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
⁷ University Medical Center Groningen, Department of General Practice, University of Groningen, Groningen, Netherlands.
⁸ Academic Medical Centre, Department of Psychiatry, Amsterdam UMC, Amsterdam, Netherlands.

Abstract

Purpose of article: In a previous pilot randomized controlled trial including 54 pregnant women with depression, maternal mood improved after Cognitive Behavioural Therapy (CBT) compared to treatment as usual (TAU), showing medium to large effect sizes. The effect persisted up to 9 months postpartum, with infant outcomes also showing medium to large effects favoring CBT in various child domains. This perspective article summarizes the results of a follow-up that was performed approximately 5 years later in the same cohort, assessing the effects of antenatal Cognitive Behavioural Therapy for depression and anxiety on child buccal cell DNA-methylation, brain morphology, behavior and cognition.

Findings: Children from the CBT group had overall lower DNA-methylation compared to children from the TAU group. Mean DNA-methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups. Children from the CBT group had a thicker right lateral occipital cortex and lingual gyrus. In the CBT group, Voxel-Based-Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe, and fixel-based analysis revealed reduced fiber-bundle-cross-section in the Fornix, the Optical Tract, and the Stria Terminalis. No differences were observed in full-scale IQ or Total Problems Score. When the total of hypotheses tests in this study was considered, differences in DNA-methylation and brain measurements were no longer significant.

Summary: Our explorative findings suggest that antenatal depression treatment decreases overall child DNA-methylation, increases cortical thickness, and decreases white matter fiber-bundle cross-section in regions involved in cognitive function and the stress response. Nevertheless, larger studies are warranted to confirm our preliminary conclusion that CBT in pregnancy alters neurobiological outcomes in children. Clinical relevance remains unclear as we found no effects of antenatal CBT on child behavior or cognition (yet).

Keywords: Cognitive Behavioural Therapy; anxiety; depression; neurodevelopment; offspring; pregnancy; programming.