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

Objective: Adverse life experiences (ALEs) increase the susceptibility to functional (somatoform/dissociative) symptoms, likely through neurodevelopmental effects. This analysis aimed to illuminate potential genetic influences in neuroanatomical variation related to functional symptoms and ALEs in patients with functional seizures. Methods: Questionnaires, structural brain MRIs and Allen Human Brain Atlas gene expression information were used to probe the intersection of functional symptom severity (Somatoform Dissociation Questionnaire, SDQ-20), ALE burden, and gray matter volumes in 20 patients with functional seizures. Results: Functional symptom severity positively correlated with the extent of sexual trauma, emotional neglect, and threat to life experiences. In voxel-based morphometry analyses, increased SDQ-20 scores related to decreased bilateral insula, left orbitofrontal, right amygdala, and perigenual and posterior cingulate gray matter volumes. Left insula findings held adjusted for psychiatric comorbidities. Increased sexual trauma burden correlated with decreased right posterior insula and putamen volumes; increased emotional neglect related to decreased bilateral insula and right amygdala volumes. The sexual trauma-right insula/putamen and emotional neglect-right amygdala relationships held adjusting for individual differences in psychiatric comorbidities. When probing the intersection of symptom severity and sexual trauma volumetric findings, genes overrepresented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways were spatially correlated. This set of genes was over-expressed in cortical and amygdala development. Conclusion: ALEs and functional symptom severity were associated with gray matter alterations in cingulo-insular and amygdala areas. Transcriptomic analysis of this anatomical variation revealed a potential involvement of several receptor signaling pathways.