神经质的
精神分裂症(面向对象编程)
多基因风险评分
年轻人
神经科学
亚临床感染
心理学
医学
生物
内科学
发展心理学
精神科
遗传学
单核苷酸多态性
自闭症
基因型
基因
自闭症谱系障碍
作者
Roberta Passiatore,Linda A. Antonucci,Thomas P. DeRamus,Leonardo Fazio,Giuseppe Stolfa,Leonardo Sportelli,Gianluca C. Kikidis,Giuseppe Blasi,Qiang Chen,Juergen Dukart,Aaron L. Goldman,Venkata S. Mattay,Teresa Popolizio,Antonio Rampino,Fabio Sambataro,Pierluigi Selvaggi,William Ulrich,Daniel R. Weinberger,Alessandro Bertolino,Vince D. Calhoun,Giulio Pergola
标识
DOI:10.1073/pnas.2221533120
摘要
Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R2 varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.
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