Soni S, Whittington J, Holland A J, Webb T, Maina E N, Boer H, Clarke D
Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, UK.
Psychol Med. 2008 Oct;38(10):1505-14. doi: 10.1017/S0033291707002504. Epub 2008 Jan 4.
Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader-Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.
The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.
Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.
Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a 'two-hit' hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.
精神病性疾病与普拉德-威利综合征（PWS）的母源性单亲二体（mUPD）遗传亚型密切相关，但与缺失亚型（delPWS）无关。本研究调查了与PWS相关的精神疾病的临床特征。我们考虑了可能导致精神病性疾病发生的遗传及其他机制，主要针对那些患有mUPD的患者。
研究样本包括119名经基因确诊的PWS患者，其中46名有精神疾病史。使用PAS-ADD、OPCRIT、家族史和生活事件问卷，从这46名患者中获取了详细的临床和家族精神病史。
mUPD患者的精神疾病发生率高于delPWS患者（22/34对比24/85，p<0.001）。两种遗传亚型的精神疾病谱均类似于伴有或不伴有精神病性症状的非典型情感障碍。delPWS患者更易患非精神病性抑郁疾病（p=0.005），而mUPD患者更易患伴有精神病性症状的双相情感障碍（p=0.00005）。患有delPWS且有精神病性疾病的患者情感障碍家族史增加。这一情况仅局限于他们的母亲。
PWS中的精神疾病主要是具有非典型特征的情感障碍。mUPD患者中疾病的患病率及可能的严重程度更高。我们提出一个“双打击”假说，涉及15号染色体上的印记基因，用于解释PWS患者中情感性精神病的发生，无论其遗传亚型如何。
