To begin addressing question, we used  transdiagnostic-based perspective, to investigate variants in genes relevant to stress-related disorders and/or associated endophenotypes, predicted behavioral and circuit-level phenotype of FMD. We also assessed  effects of childhood trauma (CT) and gene x CT interactions.

Functional movement disorders (FMD) are common and highly disabling, still little is known about their neurobiological underpinnings, particularly with regard to the contribution of genetic factors. FMD share a common core of bio-behavioral alterations with stress-related disorders, including heightened stress reactivity and connectivity in areas involved in emotional processing, may share overlapping genetic and neurobiological substrates.

DNA samples were obtained from 77 patients with a ‘clinically- defined’ diagnosis of FMD. Twenty single nucleotide polymorphisms (SNPs) from 15 candidate genes (5-HT2A, 5-HT1A, 5-HTR1B, TPH1, TPH2, SLC6A4, MAO-A, CNR1, FAAH, FKBP5, CRHR1, NR3C2, BDNF, SLC1A3, COMT) were genotyped. Participants evaluated for FMD age of onset and symptom severity, psychiatric comorbidity, anxious and depressive symptomatology, and childhood trauma exposure. Resting-state functional connectivity obtained in 38 FMD patients and 38 controls. Right amygdala connectivity was analyzed using whole-brain seed-based approach.

Among the SNPs analyzed, we found that a tryptophan hydroxylase 2 (TPH2) gene polymorphism, - 703G/T (rs4570625), significantly predicted clinical and neurocircuitry manifestations of FMD. Specifically, relative to GG carriers, T carriers were characterized by FMD age of onset, and weaker connectivity between right amygdala and the middle frontal gyrus, and lingual gyrus. TPH2 polymorphism showed significant interaction with CTQ predicting symptom severity. Childhood trauma predicted anxious and depressive symptomatology, and diagnosis of depressive disorders.