Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis.
Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis.
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DOI：
10.1016/j.nicl.2017.03.001
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Mittal VA
中科院分区：
文献类型：
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作者：
Bernard JA;Orr JM;Mittal VA
对超高危青少年（UHR）精神病发展的前瞻性纵向评估可以在不存在许多通常使研究与正式精神病患者混淆的因素（抗精神病药物、药物/酒精依赖）的情况下，丰富疾病进展的神经发育视角。小脑与精神分裂症的认知功能障碍和症状严重程度有关，我们团队最近的工作表明，它也是 UHR 个体研究的一个有希望的目标。然而，小脑和小脑-丘脑-皮质网络尚未在这一关键人群中进行发育或疾病进展的研究。此外，迄今为止，尚未进行能够为我们对该领域的理解提供实质性帮助的纵向多式联运研究类型。在本次调查中，对 26 名 UHR 和 24 名健康对照青少年进行了结构化临床访谈，并在基线时进行扫描，然后在 12 个月的时间点再次进行扫描，以调查小脑-丘脑-皮质网络的功能和结构连接发展以及症状进展。我们的结果提供了 UHR 组小脑网络功能和结构异常发育的证据。至关重要的是，我们还发现基线时小脑-丘脑-皮质网络的发育和连接与阳性症状过程相关，这表明小脑网络可能是疾病进展的生物标志物。总之，这些发现为精神病的神经发育模型提供了支持，并表明小脑和相应的皮质网络对于阐明精神病的病理生理学和突出新的治疗目标可能特别重要。小脑是整个精神病谱系研究的重要目标。对有精神病风险的青少年的小脑网络进行了超过 12 个月的研究。网络发展与高危群体的控制不同。小脑皮质网络连接预测阳性症状恶化。支持精神病的神经发育模型并涉及小脑。
Prospective longitudinal evaluation of adolescents at ultra-high-risk (UHR) for the development of psychosis enables an enriched neurodevelopmental perspective of disease progression in the absence of many of the factors that typically confound research with formally psychotic patients (antipsychotic medications, drug/alcohol dependence). The cerebellum has been linked to cognitive dysfunction and symptom severity in schizophrenia and recent work from our team suggests that it is a promising target for investigation in UHR individuals as well. However, the cerebellum and cerebello-thalamo-cortical networks have not been investigated developmentally or with respect to disease progression in this critical population. Further, to date, the types of longitudinal multimodal connectivity studies that would substantially inform our understanding of this area have not yet been conducted. In the present investigation 26 UHR and 24 healthy control adolescents were administered structured clinical interviews and scanned at baseline and then again at 12-month time points to investigate both functional and structural connectivity development of cerebello-thalamo-cortical networks in conjunction with symptom progression. Our results provide evidence of abnormal functional and structural cerebellar network development in the UHR group. Crucially, we also found that cerebello-thalamo-cortical network development and connectivity at baseline are associated with positive symptom course, suggesting that cerebellar networks may be a biomarker of disease progression. Together, these findings provide support for neurodevelopmental models of psychotic disorders and suggest that the cerebellum and respective networks with the cortex may be especially important for elucidating the pathophysiology of psychosis and highlighting novel treatment targets. The cerebellum is an important target of research across the psychosis spectrum. Cerebellar networks were investigated over 12 months in youth at-risk for psychosis. Network development differs from controls in the at-risk group. Cerebello-cortical network connectivity predicts worsening positive symptoms. Supports neurodevelopmental models of psychosis and implicates the cerebellum.