Gur Raquel E, McDonald-McGinn Donna M, Moore Tyler M, Gallagher R Sean, McClellan Emily, White Lauren, Ruparel Kosha, Hillman Noah, Crowley T Blaine, McGinn Daniel E, Zackai Elaine, Emanuel Beverly S, Calkins Monica E, Roalf David R, Gur Ruben C
Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Child and Adolescent Psychiatry and Behavioral Sciences, Lifespan Brain Institute, Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, Pennsylvania, USA.
Psychol Med. 2023 Oct;53(14):6763-6772. doi: 10.1017/S0033291723000259. Epub 2023 Mar 29.
Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome.
157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS-).
We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS- group. Neurocognitive performance was generally comparable in PS+ and PS- groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS- counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change.
Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.
神经精神障碍在22q11.2缺失综合征（22q11DS）中很常见，约25%的受影响个体在成年早期会发展为精神分裂症谱系障碍。对精神病谱系特征和神经认知进行纵向评估可以确定其发展轨迹，并对功能结局产生影响。
对157名患有22q11DS的青少年进行了纵向评估，重点关注精神病理学，包括精神病谱系症状、神经认知表现和整体功能。我们对比了阳性和阴性精神病谱系症状的模式以及神经认知表现，将具有更突出精神病谱系症状（PS+）的个体与没有突出精神病症状（PS-）的个体区分开来。
我们发现两组在精神病症状轨迹和神经认知表现方面存在差异。PS+组的症状严重程度随年龄增长而增加，尤其是阴性症状和一般非特异性症状。相应地，他们的功能水平比PS-组更差，且恶化得更迅速。PS+组和PS-组的神经认知表现总体相当，并呈现出相似的与年龄相关的轨迹。然而，执行功能的恶化使PS+组与PS-组的对应个体有所区别。值得注意的是，在所检查的三项执行功能测量中，只有工作记忆在两组之间的变化率上存在显著差异。最后，结构方程模型表明神经认知衰退推动了临床变化。
具有更突出精神病特征的22q11DS青少年表现出症状恶化和功能衰退，这是由神经认知衰退驱动的，其中大部分与执行功能特别是工作记忆有关。这些结果强调了工作记忆在精神病发展进程中的重要性。
