Right frontal cingulate cortex mediates the effect of prenatal complications on youth internalizing behaviors

Abstract

Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions.

Fig. 1. Mediation model results.

Estimated coefficients for mediation models investigating direct and indirect effects of pregnancy complications on withdrawn behavior mediated by gray matter volume in the right superior medial frontal gyrus (A, mediated model #1) and in the right anterior cingulate cortex (B, mediated model #2). c: total effect of pregnancy complications on withdrawn. c’: direct effect of pregnancy complications on withdrawn. a: direct effect of pregnancy complications on gray matter volume. b: direct effect of gray matter volume on withdrawn. *: p_Bonf < 0.05 (Bonferroni corrected, N = 2). **: p_Bonf < 0.01 (Bonferroni corrected, N = 2). R: right hemisphere.