O'Hora Kathleen P, Zhang Zizhao, Vajdi Ariana, Kushan-Wells Leila, Huang Zhengyi Sissi, Pacheco-Hansen Laura, Roof Elizabeth, Holland Anthony, Gur Ruben C, Bearden Carrie E
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States.
Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, United States.
Front Psychiatry. 2022 Apr 13;13:868536. doi: 10.3389/fpsyt.2022.868536. eCollection 2022.
Prader Willi Syndrome (PWS) is a genetic disorder caused by the absence of expression of the paternal copies of maternally imprinted gene(s) located at 15q11-q13. While the physical and medical characteristics of PWS, including short stature, hyperphagia and endocrine dysfunction are well-characterized, systematic investigation of the long-recognized psychiatric manifestations has been recent.
Here, we report on the first remote (web-based) assessment of neurobehavioral traits, including psychosis-risk symptoms (Prodromal Questionnaire-Brief Version; PQ-B) and sleep behaviors (Pittsburgh Sleep Quality Index), in a cohort of 128 participants with PWS, of whom 48% had a paternal deletion, 36% uniparental disomy, 2.4% an imprinting mutation and 13% unknown mutation (mean age 19.3 years ± 8.4; 53.9% female). We aimed to identify the most informative variables that contribute to psychosis-risk symptoms. Multiple domains of cognition (accuracy and speed) were also assessed in a subset of PWS participants ( = 39) using the Penn Computerized Neurocognitive Battery (Penn-CNB).
Individuals with PWS reported a range of psychosis-risk symptoms, with over half reporting cognitive disorganization (63.1%) and about one third reporting unusual beliefs (38.6%) and/or suspiciousness (33.3%). Subjectively-reported sleep quality, nap frequency, sleep duration, sleep disturbance, and daytime dysfunction were significant predictors of psychosis-risk symptom frequency and severity (all < 0.029). Sleep disturbance ratings were the strongest predictors of psychosis-risk symptoms. Regarding cognition, individuals with PWS showed the most prominent deficits in accuracy on measures of social cognition involving faces, namely Face Memory, Age Differentiation and Emotion Recognition, and greatest slowing on measures of Attention and Emotion Recognition. However, there were no significant differences in psychosis-risk symptoms or cognitive performance as a function of PWS genetic subtype.
PWS is associated with a high prevalence of distressing psychosis-risk symptoms, which are associated with sleep disturbance. Findings indicate that self/parent-reported neurobehavioral symptoms and cognition can be assessed remotely in individuals with PWS, which has implications for future large-scale investigations of rare neurogenetic disorders.
普拉德-威利综合征（PWS）是一种遗传性疾病，由位于15q11-q13的母系印记基因的父系拷贝缺失所致。虽然PWS的身体和医学特征，包括身材矮小、食欲亢进和内分泌功能障碍已得到充分描述，但对长期以来公认的精神症状的系统研究却是最近才开展的。
在此，我们报告了对128名PWS患者进行的首次远程（基于网络）神经行为特征评估，包括精神病风险症状（前驱症状问卷简版；PQ-B）和睡眠行为（匹兹堡睡眠质量指数）。其中48%的患者存在父系缺失，36%为单亲二体，2.4%为印记突变，13%的突变情况未知（平均年龄19.3岁±8.4；53.9%为女性）。我们旨在确定导致精神病风险症状的最具信息量的变量。还使用宾夕法尼亚计算机化神经认知测验（Penn-CNB）对一部分PWS患者（n = 39）的多个认知领域（准确性和速度）进行了评估。
PWS患者报告了一系列精神病风险症状，超过一半的患者报告存在认知紊乱（63.1%），约三分之一的患者报告存在异常信念（38.6%）和/或多疑（33.3%）。主观报告的睡眠质量、午睡频率、睡眠时间、睡眠障碍和日间功能障碍是精神病风险症状频率和严重程度的显著预测因素（均p < 0.029）。睡眠障碍评分是精神病风险症状的最强预测因素。在认知方面，PWS患者在涉及面孔的社会认知测量（即面孔记忆、年龄辨别和情绪识别）上准确性方面表现出最突出的缺陷，在注意力和情绪识别测量上表现出最大程度的反应迟缓。然而，精神病风险症状或认知表现并未因PWS基因亚型而存在显著差异。
PWS与令人苦恼的精神病风险症状的高患病率相关，这些症状与睡眠障碍有关。研究结果表明，可以对PWS患者进行远程自我/家长报告的神经行为症状和认知评估，这对未来罕见神经遗传性疾病的大规模研究具有重要意义。
