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

Inflammatory pathways predict antidepressant treatment non-response among individuals with major depression; yet, this phenomenon may have broader transdiagnostic and transtherapeutic relevance. Among traumaexposed mothers (Mage = 32 years) and their young children (Mage = 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 pretreatment, CD14 + monocytes isolated, gene expression derived from RNA sequencing (n = 34; Illumina HiSeq 4000; TruSeq cDNA 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 < 0.01). Nonetheless, a higher pre-treatment maternal pro-inflammatory imbalance of M1like versus M2-like macrophage-associated RNA expression (M1/M2) (ss = 0.476, p = .004) and IL-1ss (ss=0.333, 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 = 0.78). Additionally, higher M1/M2 predicted lesser decline in maternal depressive symptoms (ss = 0.556, 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 = 0.318-0.429, p's < 0.01), while M1/M2 and CRP were marginally associated with poorer PTSD symptom improvement (ss's = 0.295-0.333, p's < 0.056). 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.