St. George's & Institute of Psychiatry, University of London, Child & Adolescent Mental Health Services, South London & Maudsley Foundation NHS Trust, UK National Autistic Society, London, UK.
Curr Opin Psychiatry. 2011 Sep;24(5):387-97. doi: 10.1097/YCO.0b013e328349bb77.
Advances in developmental neuropsychiatry and the mental health needs of people with intellectual disability are creating ever greater understanding of the critical associations between human genome variations and psychological functioning throughout lifespan and across the entire intellectual ability spectrum. This review highlights the recent developments and their clinical implications for people with fragile X syndrome.
There is substantial evidence for individuals of all ages and intellectual abilities being prone to psychological profiles determined not only by having a fragile X gene full mutation, but also by having premutations and intermediate alleles. The importance of these genetic contributors to mental life, if anything, increases with age. Premutation carriers are prone to neurodegenerative mid-life fragile X tremor-ataxia syndrome. Women with premutations experience premature ovarian insufficiency. Imbalances in the (gamma amino butyrie acid)-glutamate mediated postsynaptic cascade central neuronal pathways are a current focus of psychopharmacological enquiry, giving the hope of syndrome-specific medical treatments.
Findings from genetic, neurological, biochemical, psychological and pharmacological research are combining to revolutionize understanding of the pathogenesis of developmental and psychological disabilities affecting individuals with fragile X syndrome irrespective of age, intelligence level and gene mutation status. Results of syndrome-specific medication trials are awaited.
发展神经精神医学的进步以及智力障碍人群的心理健康需求，使得人们越来越了解人类基因组变异与整个生命周期和整个智力能力范围内的心理功能之间的关键关联。这篇综述强调了最近的发展及其对脆性 X 综合征患者的临床意义。
大量证据表明，所有年龄段和智力能力的个体都容易出现心理特征，这些特征不仅取决于是否存在完整的脆性 X 基因突变，还取决于是否存在前突变和中间等位基因。这些遗传因素对精神生活的重要性，如果有的话，会随着年龄的增长而增加。前突变携带者易患神经退行性脆性 X 震颤共济失调综合征。携带前突变的女性会出现卵巢早衰。（γ-氨基丁酸）-谷氨酸介导的突触后级联中枢神经元途径的失衡是当前精神药理学研究的重点，为综合征特异性的医学治疗带来了希望。
遗传、神经、生化、心理和药理学研究的结果正在结合起来，彻底改变了对影响脆性 X 综合征患者的发育和心理障碍的发病机制的理解，无论其年龄、智力水平和基因突变状态如何。正在等待针对该综合征的药物试验结果。
