Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern, 3012 Bern, Switzerland; University of Zurich, Psychiatric University Hospital Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, 8032 Zurich, Switzerland.
Department of Neurology, Psychosomatic Medicine Unit, Inselspital Bern University Hospital, University of Bern, 3012 Bern, Switzerland; Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.
J Psychosom Res. 2024 Nov;186:111909. doi: 10.1016/j.jpsychores.2024.111909. Epub 2024 Aug 30.
We studied gene-environment, as well as gene-gene interaction to elucidate their effects on symptom severity and predict clinical outcomes in functional neurological disorders (FND).
Eighty-five patients with mixed FND were genotyped for ten single-nucleotide polymorphisms (SNP) from seven different stress-related genes. We tested cross-sectionally the association between genotype and the symptomatology of FND (symptom severity assessed with the examiner-based clinical global impression score [CGI] and age of onset). Clinical outcome was assessed in 52 patients who participated in a follow-up clinical visit after eight months (following their individual therapies as usual). We tested longitudinally the association between genotype and clinical outcome in FND. We examined the contribution of each SNP and their interaction between them to FND symptomatology and outcome.
We identified a nominal association between tryptophan hydroxylase 1 (TPH1) rs1800532 and symptom severity (CGI) in FND under a codominant model (T/T: ß = 2.31, se = 0.57; G/T: ß = -0.18, se = 0.29, P = 0.035), with minor allele (T) carriers presenting more severe symptoms. An association was identified between TPH1 and clinical outcome, suggesting that major allele (G) carriers were more likely to have an improved outcome under a codominant model (G/T: OR = 0.18, CI = [0.02-1.34]; T/T: OR = 2.08, CI = [0.30-14.53], P = 0.041). Our analyses suggested a significant gene-gene interaction for TPH2 (rs4570625) and OXTR (rs2254298) on symptom severity, and a significant gene-gene interaction for TPH1, TPH2 and BDNF (rs1491850) on clinical outcome.
FND might arise from a complex interplay between individual predisposing risk genes involved in the serotonergic pathway and their gene-gene interactions.
我们研究了基因-环境以及基因-基因相互作用，以阐明它们对功能性神经障碍（FND）症状严重程度的影响，并预测其临床结局。
对 85 例混合性 FND 患者进行了来自 7 个不同应激相关基因的 10 个单核苷酸多态性（SNP）的基因分型。我们横断面上检测了基因型与 FND 症状的相关性（使用基于检查者的临床总体印象评分[CGI]和发病年龄评估症状严重程度）。52 例患者在 8 个月后（按各自的常规治疗进行随访）参加了随访临床就诊，我们对其进行了纵向检测基因型与 FND 临床结局的相关性。我们检测了每个 SNP 及其相互作用对 FND 症状和结局的贡献。
在显性模型下，我们发现色氨酸羟化酶 1（TPH1）rs1800532 与 FND 症状严重程度（CGI）之间存在名义关联（T/T：β=2.31，se=0.57；G/T：β=-0.18，se=0.29，P=0.035），携带次要等位基因（T）的患者症状更严重。在显性模型下，我们发现 TPH1 与临床结局之间存在关联，表明主要等位基因（G）携带者的结局更可能改善（G/T：OR=0.18，CI=[0.02-1.34]；T/T：OR=2.08，CI=[0.30-14.53]，P=0.041）。我们的分析表明，TPH2（rs4570625）和 OXTR（rs2254298）对症状严重程度存在显著的基因-基因相互作用，而 TPH1、TPH2 和 BDNF（rs1491850）对临床结局存在显著的基因-基因相互作用。
FND 可能是涉及 5-羟色胺能途径的个体易感性风险基因及其基因-基因相互作用之间复杂相互作用的结果。
