Kraguljac Nina Vanessa, Monroe William Stonewall, Anthony Thomas, Jindal Ripu Daman, Hill Harrison, Lahti Adrienne Carol
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham.
Department of Electrical and Computer Engineering/ IT Research Computing, University of Alabama at Birmingham.
Neuroimage Rep. 2021 Mar;1(1). doi: 10.1016/j.ynirp.2021.100005. Epub 2021 Mar 4.
Diffusion tensor imaging suggests that white matter alterations are already evident in first episode psychosis patients (FEP) and may become more prominent as the duration of untreated psychosis (DUP) increases. But because the tensor model lacks specificity, it remains unclear how to interpret findings on a biological level. Here, we used a biophysical diffusion model, Neurite Orientation Dispersion and Density Imaging (NODDI), to map microarchitecture in FEP, and to investigate associations between DUP and microarchitectural integrity.
We scanned 78 antipsychotic medication-naïve FEP and 64 healthy controls using a multi-shell diffusion weighted sequence and used the NODDI toolbox to compute neurite density (ND), orientation dispersion index (ODI) and extracellular free water (FW) maps. AFNI's 3dttest++ was used to compare diffusion maps between groups and to perform regression analyses with DUP.
We found that ND was decreased in commissural and association fibers but increased in projection fibers in FEP. ODI was largely increased regardless of fiber type, and FW showed a mix of increase in decrease across fiber tracts. We also demonstrated associations between DUP and microarchitecture for all NODDI indices.
We demonstrated that complex microarchitecture abnormalities are already evident in antipsychotic-naïve FEP. ND alterations are differentially expressed depending on fiber type, while decreased fiber complexity appears to be a uniform marker of white matter deficit in the illness. Importantly, we identified an empirical link between longer DUP and greater white matter pathology across NODDI indices, underscoring the critical importance of early intervention in this devastating illness.
扩散张量成像表明，首发精神病患者（FEP）的白质改变已经很明显，并且可能随着未治疗精神病持续时间（DUP）的增加而变得更加突出。但由于张量模型缺乏特异性，目前仍不清楚如何在生物学层面解释这些发现。在此，我们使用了一种生物物理扩散模型，即神经突方向离散度与密度成像（NODDI），来绘制FEP患者的微观结构，并研究DUP与微观结构完整性之间的关联。
我们使用多壳扩散加权序列对78例未服用抗精神病药物的FEP患者和64名健康对照进行扫描，并使用NODDI工具箱计算神经突密度（ND）、方向离散度指数（ODI）和细胞外自由水（FW）图。使用AFNI的3dttest++比较两组之间的扩散图，并对DUP进行回归分析。
我们发现，FEP患者连合纤维和联合纤维中的ND降低，但投射纤维中的ND增加。无论纤维类型如何，ODI大多增加，FW在各纤维束中呈现出增加和减少的混合情况。我们还证明了所有NODDI指数的DUP与微观结构之间的关联。
我们证明，在未服用抗精神病药物的FEP患者中，复杂的微观结构异常已经很明显。ND改变根据纤维类型而有差异地表达，而纤维复杂性降低似乎是该疾病中白质缺陷的一个统一标志。重要的是，我们确定了较长的DUP与跨NODDI指数的更大白质病变之间的经验联系，强调了早期干预在这种毁灭性疾病中的至关重要性。
