Cord serum cytokines at birth and children's trajectories of mood dysregulation symptoms from 3 to 8 years: The EDEN birth cohort

Marie Herbein; Susana Barbosa; Ophélie Collet; Olfa Khalfallah; Marie Navarro; Marion Bailhache; Nicolas Iv; Bruno Aouizerate; Anne-Laure Sutter-Dallay; Muriel Koehl; Lucile Capuron; Pierre Ellul; Hugo Peyre; Judith Van der Waerden; Maria Melchior; Sylvana Côté; Barbara Heude; Nicolas Glaichenhaus; Laetitia Davidovic; Cedric Galera

doi:10.1016/j.bbih.2024.100768

Cord serum cytokines at birth and children's trajectories of mood dysregulation symptoms from 3 to 8 years: The EDEN birth cohort

Brain Behav Immun Health. 2024 Mar 29:38:100768. doi: 10.1016/j.bbih.2024.100768. eCollection 2024 Jul.

Authors

Marie Herbein^{1

2

3}, Susana Barbosa^{4

5}, Ophélie Collet^{1

6}, Olfa Khalfallah^{4

5}, Marie Navarro^{1

2}, Marion Bailhache^{1

2

7}, Nicolas Iv^{1

2}, Bruno Aouizerate^{1

3

8}, Anne-Laure Sutter-Dallay^{2

3}, Muriel Koehl^{1

9}, Lucile Capuron^{1

8}, Pierre Ellul^{10

11}, Hugo Peyre^{10

12

13}, Judith Van der Waerden¹⁴, Maria Melchior¹⁴, Sylvana Côté^{1

2

6

15}, Barbara Heude^{16

17}, Nicolas Glaichenhaus^{4

5

18}, Laetitia Davidovic^{4

5

18}, Cedric Galera^{1

2

3

6}

Affiliations

¹ University of Bordeaux, France.
² INSERM, Bordeaux Population Health Center, UMR1219, France.
³ Centre Hospitalier Perrens, Bordeaux, France.
⁴ Université Côte d'Azur, Nice, France.
⁵ Centre National de Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
⁶ Research Unit on Children's Psychosocial Maladjustment, Montreal, Canada.
⁷ Centre Hospitalier Universitaire de Bordeaux, Département de Pédiatrie, France.
⁸ INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France.
⁹ INSERM, Neurocentre Magendie, UMR1215, Bordeaux, France.
¹⁰ Robert Debré Hospital, Child and Adolescent department, APHP, Paris University, Paris, France.
¹¹ Immunology-Immunopathology-Immunotherapy (i3), UMRS 959, INSERM, Paris, France.
¹² Centre de Ressource Autisme Languedoc-Roussillon et Centre d'Excellence sur l'Autisme et les Troubles du Neurodéveloppement (CeAND), CHU Montpellier, Montpellier, France.
¹³ Université Paris Saclay, UVSQ, Inserm, CESP, Tem DevPsy, 94807, Villejuif, France.
¹⁴ INSERM U1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Équipe de Recherche en Épidémiologie Sociale, Paris, France.
¹⁵ University of Montreal, Department of Social and Preventive Medicine, Montreal, Canada.
¹⁶ Université de Paris, Centre for Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, F-75004, Paris, France.
¹⁷ Paris University, France.
¹⁸ Fondation FondaMental, Créteil, France.

Abstract

There is growing evidence that in utero imbalance immune activity plays a role in the development of neurodevelopmental and psychiatric disorders in children. Mood dysregulation (MD) is a debilitating transnosographic syndrome whose underlying pathophysiological mechanisms could be revealed by studying its biomarkers using the Research Domain Criteria (RDoC) model. Our aim was to study the association between the network of cord serum cytokines, and mood dysregulation trajectories in offsprings between 3 and 8 years of age. We used the data of a study nested in the French birth cohort EDEN that took place from 2003 to 2014 and followed mother-child dyads from the second trimester of pregnancy until the children were 8 years of age. The 2002 mother-child dyads were recruited from the general population through their pregnancy follow-up in two French university hospitals. 871 of them were included in the nested cohort and cord serum cytokine levels were measured at birth. Children's mood dysregulation symptoms were assessed with the Strengths and Difficulties Questionnaire Dysregulation Profile at the ages 3, 5 and 8 years in order to model their mood dysregulation trajectories. Out of the 871 participating dyads, 53% of the children were male. 2.1% of the children presented a high mood dysregulation trajectory whereas the others were considered as physiological variations. We found a significant negative association between TNF-α cord serum levels and a high mood dysregulation trajectory when considering confounding factors such as maternal depression during pregnancy (adjusted Odds Ratio (aOR) = 0.35, 95% Confidence Interval (CI) [0.18-0.67]). Immune imbalance at birth could play a role in the onset of mood dysregulation symptoms. Our findings throw new light on putative immune mechanisms implicated in the development of mood dysregulation and should lead to future animal and epidemiological studies.

Keywords: Birth cohort; Child and adolescent psychiatry; Cytokines; DMDD; Epidemiology; Immune system; Irritability; Pregnancy; TNFα.