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Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes
Biological Psychiatry ( IF 10.6 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.biopsych.2019.12.005
Rafael Romero-Garcia 1 , Jakob Seidlitz 1 , Kirstie J Whitaker 2 , Sarah E Morgan 1 , Peter Fonagy 3 , Raymond J Dolan 4 , Peter B Jones 5 , Ian M Goodyer 5 , John Suckling 1 , , Petra E Vértes 6 , Edward T Bullmore 5
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Background Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. Methods We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14–25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. Results Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate–corrected ps < .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive “hubs” such as parvalbumin and calmodulin. Conclusions Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.

中文翻译:

健康青春期皮质分裂型相关磁化与精神分裂症相关基因的表达位于同一位置

背景 遗传风险被认为会导致一系列精神分裂症样特征的临床变异,但将基因组变异与精神分裂症经历和行为机械联系起来的大脑结构的潜在变化尚不清楚。方法 我们使用自我报告的问卷评估精神分裂症,并测量磁化转移作为 248 名健康年轻人(14-25 岁)68 个脑区皮质内髓鞘形成的假定微结构磁共振成像标记。我们使用规范的成人大脑基因表达数据和偏最小二乘分析来找到与分裂型相关磁化的皮质图最一致的加权基因表达模式。结果 磁化强度与双侧后扣带皮层和楔前叶的分裂型显着相关(对于混乱的分裂型,也在内侧前额叶皮层中;所有错误发现率校正 ps < .05),这些区域是专门用于社交的默认模式网络区域和记忆功能。在与精神分裂症相关磁化共处的全基因组表达图上权重最大的基因富集了在先前两项精神分裂症脑基因表达病例对照组织学研究中显着下调的基因。相反,负权重最大的基因富含精神分裂症中转录上调的基因。正权重(下调)的基因针对神经元,特别是神经元间的隶属关系进行了富集,并编码了一个蛋白质网络,该网络包含一些高度相互作用的“中心”,例如小清蛋白和钙调蛋白。结论 皮质内磁化的微结构磁共振成像图可以与精神分裂症的行为特征和精神分裂症基因表达失调的先前组织学数据联系起来。
更新日期:2020-08-01
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