An immunogenomic phenotype predicting behavioral treatment response: Toward precision psychiatry for mothers and children with trauma exposure

Abstract

Inflammatory pathways predict antidepressant treatment non-response among individuals with major depression; yet, this phenomenon may have broader transdiagnostic and transtherapeutic relevance. Among trauma-exposed mothers (Mage=32 years) and their young children (M=4 years), we tested whether genomic and proteomic biomarkers of pro-inflammatory imbalance prospectively predicted treatment response (PTSD and depression) to an empirically-supported behavioral treatment. Forty-three mother-child dyads without chronic disease completed Child Parent Psychotherapy (CPP) for roughly 9 months. Maternal blood was drawn pre-treatment, CD14+ monocytes isolated, gene expression derived from RNA sequencing (n=34; Illumina HiSeq 4000;TruSeqcDNA library), and serum assayed (n=43) for C-Reactive Protein (CRP) and interleukin-1ß (IL-1ß). Symptoms of PTSD and depression decreased significantly from pre- to post-treatment for both mothers and children (all p s<.01). Nonetheless, a higher pre-treatment maternal pro-inflammatory imbalance of M1-like versus M2-like macrophage-associated RNA expression (M1/M2)(ß=.476, p=.004) and IL-1ß (ß=.333, p=.029), but not CRP, predicted lesser improvements in maternal PTSD symptoms, unadjusted and adjusting for maternal age, BMI, ethnicity, antidepressant use, income, education, and US birth. Only higher pre-treatment M1/M2 predicted a clinically-relevant threshold of PTSD non-response among mothers (OR=3.364, p=.015; ROC-AUC=.78). Additionally, higher M1/M2 predicted lesser decline in maternal depressive symptoms (ß=.556, p=.001), though not independent of PTSD symptoms. For child outcomes, higher maternal IL-1ß significantly predicted poorer PTSD and depression symptom trajectories (ß s=.318-.429, p s<.01), while M1/M2 and CRP were marginally associated with poorer PTSD symptom improvement (ß s=.295-.333, p s<.056). Pre-treatment pro-inflammatory imbalance prospectively predicts poorer transdiagnostic symptom response to an empirically-supported behavioral treatment for trauma-exposed women and their young children.