Department of Psychological Medicine, The Henry Wellcome Building for Biomedical Research in Wales, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, U.K.
Br J Dermatol. 2010 Sep;163(3):515-22. doi: 10.1111/j.1365-2133.2010.09834.x. Epub 2010 Apr 29.
Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain.
To conduct the first systematic investigation of the neuropsychiatric phenotype in DD.
One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD.
Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features.
These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.
Darier 病（DD）是一种罕见的常染色体显性遗传性皮肤病，皮肤科医生经常报告该病同时伴有神经精神异常。该病是由单个基因 ATP2A2 的突变引起的，该基因在皮肤和大脑中表达。
对 DD 的神经精神表型进行首次系统研究。
对 100 名无血缘关系的 DD 患者进行一系列标准化神经精神评估。还收集了 DD 的一些临床特征的数据。
DD 患者一生中出现情绪障碍（50%）的几率较高，尤其是重度抑郁症（30%）和双相情感障碍（4%），以及自杀企图（13%）和自杀意念（31%）。与一般人群数据相比，DD 患者的这些情况更为常见。该样本中癫痫（3%）的患病率也高于一般人群。DD 的特定皮肤病特征与精神症状的存在之间没有一致的关联。
这些发现强调了临床医生在 DD 中评估和识别神经精神症状的必要性。结果并不表明神经精神症状仅仅是对患有皮肤病的心理反应，而是与多效性假说一致，即 ATP2A2 基因突变除了引起 DD 外，还使神经精神特征易感性增加。需要进一步研究以调查 ATP2A2 内致病突变的类型和/或位置与所表达的神经精神表型之间的基因型-表型相关性。
