Linking gene expression patterns and brain morphometry to trauma and symptom severity in patients with functional seizures

Abstract

Within stress-diathesis models, adverse life experiences (ALEs) increase the susceptibility to functional neurological symptoms through neuroplasticity effects. We aimed to characterize potential genetic influences on this relationship in 20 patients with functional seizures. Questionnaires, structural MRIs and Allen Human Brain Atlas gene expression information were used to probe the intersection of symptom severity (Somatoform Dissociation Questionnaire, SDQ-20), ALE burden, and gray matter volumes. SDQ-20 scores positively correlated with sexual trauma, emotional neglect, and threat to life experiences. Higher SDQ-20 scores related to lower bilateral insula, left orbitofrontal, right amygdala, and perigenual/posterior cingulate volumes. Higher sexual trauma burden correlated with lower right posterior insula and putamen volumes; higher emotional neglect related to lower bilateral insula/right amygdala volumes. Findings in left insula/ventral precentral gyrus (SDQ-20), right insula/putamen (sexual trauma), and right amygdala (emotional neglect) held when controlling for comorbid psychopathology. At the intersection of symptom severity and sexual trauma volumetric findings, genes overrepresented in adrenergic, serotonergic, and oxytocin receptor signaling as well as in cortical and amygdala development were spatially correlated. In conclusion, ALEs and symptom severity were associated with gray matter volumes in cingulo-insular and amygdala areas, spatially overlapping with expression patterns of genes involved in stress-related signaling and neurodevelopment.