From the Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada (Drobinin, Schmidt, Uher); the Nova Scotia Health Authority, Halifax, NS (Drobinin, van Gestel, Zwicker, MacKenzie, Cumby, Patterson, Vallis, Campbell, Helmick, Alda, Bowen, Uher); the Department of Pathology, Dalhousie University, Halifax, NS (Zwicker, Uher); the Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS (MacKenzie, Patterson, Uher); the Department of Psychiatry, Dalhousie University, Halifax, NS (Vallis, Helmick, Alda, Uher); the Department of Medicine, Dalhousie University, Halifax, NS (Campbell); and the Department of Diagnostic Radiology, Dalhousie University, Halifax, NS (Bowen).
J Psychiatry Neurosci. 2020 Mar 1;45(2):125-133. doi: 10.1503/jpn.180144.
Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms.
We collected MRIs and examined the local gyrification index in a sample of 110 youth (mean age ± standard deviation 14.0 ± 3.7 yr; range 9–25 yr) with a family history of severe mental illness: 48 with psychotic symptoms and 62 without. Images were processed using the Human Connectome Pipeline and FreeSurfer. We tested for group differences in local gyrification index using mixed-effects generalized linear models controlling for age, sex and familial clustering. Sensitivity analysis further controlled for intracranial volume, IQ, and stimulant and cannabis use.
Youth with psychotic symptoms displayed an overall trend toward lower cortical folding across all brain regions. After adjusting for multiple comparisons and confounders, regional reductions were localized to the frontal and occipital lobes. Specifically, the medial (B = –0.42, pFDR = 0.04) and lateral (B = –0.39, pFDR = 0.04) orbitofrontal cortices as well as the cuneus (B = –0.47, pFDR = 0.03) and the pericalcarine (B = –0.45, pFDR = 0.03) and lingual (B = –0.38, pFDR = 0.04) gyri.
Inference about developmental trajectories was limited by the cross-sectional data.
Psychotic symptoms in youth are associated with cortical folding deficits, even in the absence of psychotic illness. The current study helps clarify the neurodevelopmental basis of psychosis at an early stage, before medication, drug use and other confounds have had a persistent effect on the brain.
皮质折叠对于大脑的健康发育至关重要。先前的研究发现，精神疾病成年患者的皮质折叠区域减少。目前尚不清楚这些神经解剖学标志物是否存在于有亚临床精神病症状的年轻人中。
我们收集了 110 名（平均年龄 ± 标准差 14.0 ± 3.7 岁；范围 9-25 岁）有严重精神疾病家族史的年轻人（48 名有精神病症状，62 名无）的 MRI 并检查了局部脑回指数。使用 Human Connectome Pipeline 和 FreeSurfer 对图像进行处理。我们使用混合效应广义线性模型控制年龄、性别和家族聚集性，测试了局部脑回指数的组间差异。敏感性分析进一步控制了颅内体积、智商以及兴奋剂和大麻的使用。
有精神病症状的年轻人的大脑所有区域的皮质折叠总体上都较低。在调整了多重比较和混杂因素后，局部减少局限于额叶和枕叶。具体来说，内侧（B = –0.42，pFDR = 0.04）和外侧（B = –0.39，pFDR = 0.04）眶额皮质以及楔前回（B = –0.47，pFDR = 0.03）和距状回（B = –0.45，pFDR = 0.03）和舌回（B = –0.38，pFDR = 0.04）。
由于横断面数据的限制，关于发育轨迹的推论是有限的。
即使在没有精神病的情况下，年轻人的精神病症状也与皮质折叠缺陷有关。本研究有助于在药物、药物使用和其他混杂因素对大脑产生持续影响之前，阐明精神病的早期神经发育基础。
