Institute of Psychology, University of Lausanne, 1015, Lausanne, Switzerland.
School of Psychological Sciences, University of Haifa, 31905, Haifa, Israel.
Mol Psychiatry. 2022 Jul;27(7):2976-2984. doi: 10.1038/s41380-022-01543-5. Epub 2022 Apr 14.
Functional impairment is a core feature of both autism and schizophrenia spectrum disorders. While diagnostically independent, they can co-occur in the same individual at both the trait and diagnostic levels. The effect of such co-occurrence is hypothesized to worsen functional impairment. The diametric model, however, suggests that the disorders are etiologically and phenotypically diametrical, representing the extreme of a unidimensional continuum of cognition and behavior. A central prediction of this model is that functional impairment would be attenuated in individuals with mixed symptom expressions or genetic liability to both disorders. We tested this hypothesis in two clinical populations and one healthy population. In individuals with chronic schizophrenia and in individuals with first episode psychosis we evaluated the combined effect of autistic traits and positive psychotic symptoms on psychosocial functioning. In healthy carriers of alleles of copy number variants (CNVs) that confer risk for both autism and schizophrenia, we also evaluated whether variation in psychosocial functioning depended on the combined risk conferred by each CNV. Relative to individuals with biased symptom/CNV risk profiles, results show that functional impairments are attenuated in individuals with relatively equal levels of positive symptoms and autistic traits-and specifically stereotypic behaviors-, and in carriers of CNVs with relatively equal risks for either disorder. However, the pattern of effects along the "balance axis" varied across the groups, with this attenuation being generally less pronounced in individuals with high-high symptom/risk profile in the schizophrenia and CNV groups, and relatively similar for low-low and high-high individuals in the first episode psychosis group. Lower levels of functional impairments in individuals with "balanced" symptom profile or genetic risks would suggest compensation across mechanisms associated with autism and schizophrenia. CNVs that confer equal risks for both disorders may provide an entry point for investigations into such compensatory mechanisms. The co-assessment of autism and schizophrenia may contribute to personalized prognosis and stratification strategies.
功能障碍是自闭症和精神分裂谱系障碍的核心特征。虽然它们在诊断上是独立的，但在个体的特质和诊断水平上都可能同时存在。这种共病的影响被假设会加重功能障碍。然而，对角模型表明，这些疾病在病因和表型上是截然不同的，代表了认知和行为的单一维度连续体的极端。该模型的一个核心预测是，在具有混合症状表现或同时具有两种疾病遗传易感性的个体中，功能障碍会减轻。我们在两个临床人群和一个健康人群中检验了这一假设。在慢性精神分裂症患者和首发精神病患者中，我们评估了自闭症特征和阳性精神病症状对心理社会功能的综合影响。在携带自闭症和精神分裂症风险的拷贝数变异（CNV）等位基因的健康携带者中，我们还评估了心理社会功能的变化是否取决于每个 CNV 综合风险的影响。与具有偏向症状/CNV 风险特征的个体相比，结果表明，在阳性症状和自闭症特征相对平衡的个体中，特别是在刻板行为中，以及在具有相对相等的两种疾病风险的 CNV 携带者中，功能障碍会减轻。然而，沿着“平衡轴”的效应模式在各组之间有所不同，在精神分裂症和 CNV 组中，具有高-高症状/风险特征的个体中这种衰减程度通常不太明显，而在首发精神病组中，低-低和高-高个体之间则相对相似。具有“平衡”症状特征或遗传风险的个体功能障碍水平较低，可能表明与自闭症和精神分裂症相关的机制存在代偿。同时为两种疾病提供风险的 CNV 可能为研究这种代偿机制提供切入点。对自闭症和精神分裂症的共同评估可能有助于个性化预后和分层策略。
