Iannotta Federica, La Monica Ilaria, Di Iorio Maria Rosaria, Freda Vittorio, Sica Antonia, de Bartolomeis Andrea, Pastore Lucio, Iasevoli Felice, Lombardo Barbara
Section of Psychiatry, Department of Neuroscience, School of Medicine, University of Naples "Federico II", Via Sergio Pansini 5, 80131 Naples, Italy.
CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.
Int J Mol Sci. 2025 Apr 23;26(9):3970. doi: 10.3390/ijms26093970.
Schizophrenia (SCZ) is a complex mental disorder, whose pathogenesis involves both environmental and genetic factors. Genetic risk is conferred through a combination of common variants and rare mutations, with point mutations and copy number variants (CNVs). Many of the genetic variants associated with SCZ have pleiotropic effects, influencing brain development and being shared with other neurodevelopmental disorders (NDDs), such as intellectual disability (ID). This overlap supports the concept of a neurodevelopmental continuum, suggesting shared genetic risk, at least between SCZ and ID, and most presumably among SCZ and many other NDDs. Here, we describe the case of a male patient whose clinical features align with this hypothesis. He presented cognitive and behavioral impairments preceding psychotic symptoms, further reinforcing the genetic and clinical interaction between SCZ and other NDDs. The patient's genetic profile was analyzed using array comparative genomic hybridization (a-CGH) and whole-exome sequencing (WES) to investigate the genetic determinants underlying his clinical condition. The genetic testing identified variants in loci associated with both SCZ and NDDs. Our findings highlight the need to integrate genetic assessments into psychiatrists' clinical practice. Moreover, this report contributes to the current body of evidence supporting the thesis on the neurodevelopmental continuum of SCZ.
精神分裂症（SCZ）是一种复杂的精神障碍，其发病机制涉及环境和遗传因素。遗传风险通过常见变异和罕见突变的组合来传递，包括点突变和拷贝数变异（CNV）。许多与SCZ相关的遗传变异具有多效性，影响大脑发育，并与其他神经发育障碍（NDD）如智力障碍（ID）存在共同之处。这种重叠支持了神经发育连续体的概念，表明至少在SCZ和ID之间存在共同的遗传风险，很可能在SCZ和许多其他NDD之间也存在。在此，我们描述了一名男性患者的病例，其临床特征与这一假设相符。他在出现精神病症状之前就表现出认知和行为障碍，进一步强化了SCZ与其他NDD之间的遗传和临床相互作用。使用阵列比较基因组杂交（a-CGH）和全外显子测序（WES）对该患者的基因图谱进行了分析，以研究其临床状况背后的遗传决定因素。基因检测确定了与SCZ和NDD相关基因座中的变异。我们的研究结果强调了将基因评估纳入精神科医生临床实践的必要性。此外，本报告为目前支持SCZ神经发育连续体这一论点的证据体系做出了贡献。
