Karcher Nicole R, Dong Fanghong, Johnson Emma C, Paul Sarah E, Kilciksiz Can Misel, Oh Hans, Schiffman Jason, Agrawal Arpana, Bogdan Ryan, Jackson Joshua J, Barch Deanna M
bioRxiv. 2025 Jan 22:2025.01.20.633817. doi: 10.1101/2025.01.20.633817.
Psychotic-like experiences (PLEs) may arise from genetic and environmental risk leading to worsening cognitive and neural metrics over time, which in turn lead to worsening PLEs. Persistence and distress are factors that distinguish more clinically significant PLEs. Analyses used three waves of unique longitudinal Adolescent Brain Cognitive Development Study data (ages 9-13) to test whether changes in cognition and structural neural metrics attenuate associations between genetic and environmental risk with persistent distressing PLEs.
Multigroup univariate latent growth models examined three waves of cognitive metrics and global structural neural metrics separately for three PLE groups: persistent distressing PLEs (n=356), transient distressing PLEs (n=408), and low-level PLEs (n=7901). Models then examined whether changes in cognitive and structural neural metrics over time attenuated associations between genetic liability (i.e., schizophrenia polygenic risk scores/family history) or environmental risk scores (e.g., poverty) and PLE groups.
Persistent distressing PLEs showed greater decreases (i.e., more negative slopes) of cognition and neural metrics over time compared to those in low-level PLE groups. Associations between environmental risk and persistent distressing PLEs were attenuated when accounting for lowered scores over time on cognitive (e.g., picture vocabulary) and to a lesser extent neural (e.g., cortical thickness, volume) metrics.
Analyses provide novel evidence for extant theories that worsening cognition and global structural metrics may partially account for associations between environmental risk with persistent distressing PLEs.
类精神病性体验(PLEs)可能源于遗传和环境风险,随着时间的推移导致认知和神经指标恶化,进而导致PLEs恶化。持续性和痛苦程度是区分更具临床意义的PLEs的因素。分析使用了青少年大脑认知发展研究(9至13岁)的三轮独特纵向数据,以检验认知和结构神经指标的变化是否会减弱遗传和环境风险与持续性痛苦PLEs之间的关联。
多组单变量潜在增长模型分别针对三组PLEs:持续性痛苦PLEs(n = 356)、短暂性痛苦PLEs(n = 408)和低水平PLEs(n = 7901),对三轮认知指标和整体结构神经指标进行了检验。模型随后检验了随着时间推移认知和结构神经指标的变化是否会减弱遗传易感性(即精神分裂症多基因风险评分/家族史)或环境风险评分(如贫困)与PLEs组之间的关联。
与低水平PLEs组相比,持续性痛苦PLEs随着时间的推移在认知和神经指标上显示出更大的下降(即更负的斜率)。当考虑到随着时间推移认知(如图画词汇)和在较小程度上神经(如皮层厚度、体积)指标得分降低时,环境风险与持续性痛苦PLEs之间的关联减弱。
分析为现有理论提供了新证据,即认知和整体结构指标的恶化可能部分解释了环境风险与持续性痛苦PLEs之间的关联。