Sex-based variations of prefrontal structure and longitudinal symptoms in pediatric posttraumatic stress disorder

Pediatric posttraumatic stress disorder (pPTSD) is more than three times as likely to develop in trauma-exposed female youth than males. Despite the staggering sex differences in the prevalence rates of pPTSD and symptom expression, relatively little is known about the underlying biomarkers of these sex-based variations in pPTSD as compared to typically development.

The Youth PTSD study recruited 97 youth, ages of 7 and 18, to undergo comprehensive clinical assessments and T1-weighted MRI to evaluate the extent to which sex can explain PTSD-related variations in brain structure. Whole-brain VBM as well as whole-brain estimates of cortical thickness and surface area were analyzed to identify group-by-sex interactions. Finally, we tested whether current or future symptom severity was predictive of regions exhibiting sex-based variations.

Clinically, females with PTSD were significantly more likely to report exposure to and higher severity of interpersonal violence and symptoms of hyperarousal. Sex and PTSD status were predictive of gray matter across the lateral prefrontal cortex (PFC), including the ventrolateral PFC and frontal pole, where increased volume and surface area was found in PTSD females as compared to PTSD males. Interestingly, the ventrolateral prefrontal cortex and frontal pole were negatively predictive of symptoms 1 year later in only males with PTSD.

Together, these results establish that youth with PTSD exhibit sex-based variations in clinical and trauma characteristics and prefrontal cortical structure relative to normative development. This work demonstrates the importance of examining the role that sex may play in the behavioral and neurobiological presentation of pPTSD.