Immune activity at birth and later psychopathology in childhood

Susana Barbosa; Olfa Khalfallah; Anne Forhan; Cédric Galera; Barbara Heude; Nicolas Glaichenhaus; Laetitia Davidovic

doi:10.1016/j.bbih.2020.100141

Immune activity at birth and later psychopathology in childhood

Brain Behav Immun Health. 2020 Sep 10:8:100141. doi: 10.1016/j.bbih.2020.100141. eCollection 2020 Oct.

Authors

Susana Barbosa^{1

2}, Olfa Khalfallah^{1

2}, Anne Forhan³, Cédric Galera⁴, Barbara Heude³, Nicolas Glaichenhaus^{1

2}, Laetitia Davidovic^{1

2}

Affiliations

¹ Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
² Université Côte d'Azur, Nice, France.
³ Université de Paris, Institut National de la Santé et de la Recherche Médicale, Institut National de la Recherche Agronomique, Centre de Recherche en Épidémiologie et Statistiques, Paris, France.
⁴ Université Bordeaux Segalen, Charles Perrens Hospital, Child and Adolescent Psychiatry Department, Bordeaux, France.

Abstract

Disruption of neurodevelopmental trajectories can alter brain circuitry and increase the risk of psychopathology later in life. While preclinical studies have demonstrated that the immune system and cytokines influence neurodevelopment, whether immune activity and in particular which cytokines at birth are associated with psychopathology remains poorly explored in children. We used data and biological samples from 869 mother-child pairs participating in the French mother-child cohort EDEN. As proxies for immune activity at birth, we measured the levels of 27 cytokines in umbilical cord blood sera (CBS). We then explored the association between CBS cytokine levels and five psychopathological dimensions assessed in 5-year-old children using the Strengths and Difficulties Questionnaire (SDQ). Five cytokines were positively associated with psychopathology: C-X-C motif chemokine Ligand (CXCL)10, interleukin (IL)-10 and IL-12p40 with emotional symptoms, C-C motif chemokine Ligand (CCL)11 with conduct problems, and CCL11, and IL-17A with peer relationships problems. In contrast, seven cytokines were negatively associated with psychopathology: IL-7, IL-15 and Tumor Necrosis Factor (TNF)-β with emotional symptoms, CCL4 and IL-6 with conduct problems, CCL26 and IL-15 with peer relationships problems, and CCL26, IL-7, IL-15, and TNF-α with abnormal prosocial behavior. Without implying causation, these associations support the notion that cytokines influence neurodevelopment in humans and the risk of psychopathology later in life.

Keywords: Behavior; Cytokines; Inflammation; Mother-child cohort; Neurodevelopment; Psychopathology.