Maternal Autoimmunity and Inflammation are Associated with Childhood Tics and Obsessive-Compulsive Disorder: Transcriptomic Data show Common Enriched Innate Immune Pathways.

Abstract Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p=0.054), and mothers of healthy controls (p=0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p