Depth‐dependent abnormal cortical myelination in first‐episode treatment‐naïve schizophrenia

Abstract

Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first‐episode treatment‐naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal–temporal association cortex, but reduced myelination of the cingulo‐insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ.

Multimodal imaging improves brain age prediction and reveals distinct abnormalities in patients with psychiatric and neurological disorders

“…This is in line with reports of abnormal T1w/T2w in AD (Pelkmans et al 2019, Grydeland et al, 2013b). Further, emerging evidence indicates lower T1w/T2w in SZ, implicating subcortical (Iwatani et al 2015; Ganzetti, Wenderoth, and Mantini 2015) and cortical regions (Wei et al, 2020).…”

“…Further, emerging evidence indicates lower T1w/T2w in SZ, implicating subcortical (Iwatani et al 2015;Ganzetti, Wenderoth, and Mantini 2015) and cortical regions (Wei et al, 2020).…”

Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

“…Understanding the relation of genetic risk for schizophrenia to neurodevelopment can be further enhanced by contextualising the imaging-derived phenotype with maps of cortical organization. At the cellular level, a range of processes associated with healthy cortical development, such as synaptic pruning, dendritic arborization and intracortical myelination, are implicated in the development of schizophrenia and may produce regional cortical disruptions (Feinberg, 1982; Sellgren et al ., 2019; Sprooten et al ., 2019; Wei et al ., 2020). Recent advances in RNA sequencing (RNAseq) of post mortem brain tissue (Zhu et al ., 2018) allow discernment of the relative contribution of cell-types to patterns of atypical cortical morphometry (Seidlitz et al ., 2020; Writing Committee for the Attention-Deficit/Hyperactivity Disorder et al ., 2021).…”

Quantitative Macromolecular Proton Fraction Mapping Reveals Altered Cortical Myelin Profile in Schizophrenia Spectrum Disorders

“…2013 ). Recently, using T 1 w/T 2 w myelin imaging, Wei et al. (2020 ) reported increased myelin content in superficial and midcortical layers of inferior parietal lobe but decreased myelin in midcortical layers of insula and posterior cingulate regions in first-episode SSD.…”

“…2018 ). However, variation exists in terms of the extent, location, and direction of cortical myelin alterations across studies, likely confounded by the age and disease stage of patient groups involved and dependent on the cortical depth examined ( Wei et al. 2020 ).…”