Grigsby Jim, Brega Angela G, Bennett Rachael E, Bourgeois James A, Seritan Andreea L, Goodrich Glenn K, Hagerman Randi J
a Department of Psychology , University of Colorado Denver , Denver , CO , USA.
b Department of Medicine , University of Colorado Denver , Aurora , CO , USA.
Clin Neuropsychol. 2016 Aug;30(6):944-59. doi: 10.1080/13854046.2016.1185100. Epub 2016 Jun 29.
To clarify the neuropsychiatric phenotype of fragile X-associated tremor/ataxia syndrome (FXTAS), and assess the extent to which it is mediated by the dysexecutive syndrome that is a major feature of the disorder.
We examined the prevalence of clinically meaningful psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, in comparison with men with a normal allele. Measures included the Neuropsychiatric Inventory (NPI), Symptom Checklist-90-R (SCL-90-R), and the Behavioral Dyscontrol Scale, a measure of executive functioning. Between-group differences were evaluated using logistic regression, followed by a mediation analysis with ordinary least squares regression to assess the contribution of dysexecutive syndrome to the observed psychiatric domains.
Men with FXTAS showed higher rates of clinically significant symptoms overall and in specific domains: somatization, obsessive compulsive, depression, anxiety, psychoticism, agitation/aggression, apathy/indifference, irritability, and nighttime behavior problems. Post hoc analyses suggested that findings of psychoticism among men with FXTAS may be associated with participants' accurate acknowledgment of cognitive and physical dysfunction, rather than reflecting psychosis. Asymptomatic carriers showed no evidence of clinically significant psychiatric symptoms, but when all carriers were compared with men having a normal FMR1 allele, executive function deficits were found to mediate scores in several domains on both NPI and SCL-90-R.
Building on prior research, the results provide evidence that the psychiatric phenotype for men includes clinically meaningful depression, hostility, and irritability, in association with behavioral and attentional disinhibition. It is likely that these problems reflect the effects of impaired executive functioning.
明确脆性X相关震颤/共济失调综合征（FXTAS）的神经精神表型，并评估其在多大程度上由该疾病的主要特征——执行功能障碍综合征介导。
我们研究了脆性X前突变男性携带者（有或无FXTAS）中具有临床意义的精神症状的患病率，并与具有正常等位基因的男性进行比较。测量指标包括神经精神问卷（NPI）、症状自评量表-90修订版（SCL-90-R）以及行为失控量表（一种执行功能测量工具）。使用逻辑回归评估组间差异，随后采用普通最小二乘法回归进行中介分析，以评估执行功能障碍综合征对观察到的精神领域的影响。
患有FXTAS的男性总体上以及在特定领域（躯体化、强迫观念与强迫行为、抑郁、焦虑、精神病性、激越/攻击、情感淡漠、易怒及夜间行为问题）出现具有临床意义症状的比例更高。事后分析表明，患有FXTAS的男性出现的精神病性症状可能与参与者对认知和身体功能障碍的准确认知有关，而非反映精神病。无症状携带者未表现出具有临床意义的精神症状，但当将所有携带者与具有正常FMR1等位基因的男性进行比较时，发现执行功能缺陷介导了NPI和SCL-90-R多个领域的得分。
基于先前的研究，结果表明男性的精神表型包括具有临床意义的抑郁、敌意和易怒，并伴有行为和注意力抑制障碍。这些问题可能反映了执行功能受损的影响。
