Biology subjects

Sanchez, S. M.

Publications and source records attributed to Sanchez, S. M..

4 recordsLinked to original sources

bioRxiv2026

Sex-stratified fixel-based analysis reveals reduced frontal fibre density in males with first-episode of psychosis

Background: Schizophrenia has been conceptualised as a disorder of brain disconnectivity, with white matter abnormalities contributing to altered neural communication. However, fibre-specific white matter alterations in early illness and their potential sex-related differences remain insufficiently characterised. We applied fixel-based analysis to investigate sex-stratified white matter microstructural alterations in first-episode schizophrenia (FES). Methods: Diffusion MRI data from individuals with FES and healthy controls were stratified by biological sex. The male cohort included 79 patients and 29 controls, and the female cohort included 48 patients and 46 controls. Fixel-based analysis was performed separately in males and females to assess fibre density, fibre-bundle cross-section, and their combined measure. Head motion was included as a covariate in the fixel-based analyses. A descriptive follow-up voxel-scale analysis extracted mean fibre density from a binary mask derived from significant male fixels and applied the same region to the female cohort. Results: Males with first-episode schizophrenia showed significantly reduced fibre density compared with male controls, primarily in bilateral frontal white matter and a thin segment of the anterior corpus callosum. The voxel-scale follow-up confirmed lower mean fibre density in males within the significant fixel-derived mask. In contrast, females showed no significant group differences in any fixel-based metric or within the male-derived region. Conclusions: Early white matter microstructural alterations were detected in males with FES but not in females. These findings highlight a differential pattern emerging from sex-stratified analyses and support further investigation of sex-related differences in white matter alterations during the early stages of schizophrenia.

neuroscience↗

bioRxiv2025

Characterising Structural Brain Connectivity of Patients with First Episode of Psychosis

BACKGROUND AND HYPOTHESISSchizophrenia is associated with widespread neuroanatomical abnormalities affecting both grey matter and white matter (WM). Early symptoms are often linked to dysfunctions in the frontal cortex and the temporal lobe. This study investigates WM disruptions and explores how structural connectivity (SC) may contribute to the underlying mechanisms of the disorder. STUDY DESIGNWe analysed SC derived from diffusion MRI in 127 patients experiencing their first episode of schizophrenia (FES group), compared with healthy controls. Focusing on the fronto-parietal-temporal network, we examined SC across three hierarchical levels: network, node, and connection. SC metrics were compared between groups using 3-factor ANCOVA, accounting for relevant covariates. We also investigated associations between SC metrics and core positive symptoms using non-parametric correlations. RESULTSThe FES group showed significantly reduced average SC strength and global efficiency within the fronto-parietal-temporal network. At the nodal level, SC strength was significantly lower in the left inferior and middle temporal gyri (L.ITG, L.MTG), and in the right inferior parietal gyrus (R.IPG) and temporal pole (R.TP). No significant group differences emerged at the connection level. Notably, SC strength in the R.IPG was negatively correlated with Conceptual Disorganisation scores. CONCLUSIONSOur findings reveal global and regional SC disruptions in early psychosis, particularly in areas supporting cognitive, language, and executive functions. The observed association between R.IPG connectivity and Conceptual Disorganisation supports the link between disrupted SC and formal thought disorder, reinforcing the role of impaired structural integration in early psychosis.

neuroscience↗

bioRxiv2022

White Matter Brain Structure Predicts Language Performance and Learning Success

Individual differences in the ability to deal with language have long been discussed. The neural basis of these, however, is yet unknown. Here we investigated the relationship between long-range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants native language as well as the improvement thereof by multi-day training. We identified specific network motifs that indeed related white matter tractography to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance suggesting a predisposition for the individual ability to process syntactically complex sentences, which manifests itself in the white matter brain structure. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brains white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.

neuroscience↗

bioRxiv2020

DRAM1 requires PI(3,5)P2 generation by PIKfyve to deliver vesicles and their cargo to endolysosomes

Endolysosomal vesicle trafficking and autophagy are crucial degradative pathways in maintenance of cellular homeostasis. The transmembrane protein DRAM1 is a potential therapeutic target that primarily localises to endolysosomal vesicles and promotes autophagy and vesicle fusion with lysosomes. However, the molecular mechanisms underlying DRAM1-mediated vesicle fusion events remain unclear. Using high-resolution confocal microscopy in the zebrafish model, we show that mCherry-Dram1 labelled vesicles interact and fuse with early endosomes marked by PI(3)P. Following these fusion events, early endosomes mature into late endosomes in a process dependent on the conversion of PI(3)P into PI(3,5)P2 by the lipid kinase PIKfyve. Chemical inhibition of PIKfyve reduces the targeting of Dram1 to acidic endolysosomal vesicles, arresting Dram1 in multivesicular bodies, early endosomes, or non-acidified vesicles halted in their fusion with early endosomes. In conclusion, Dram1-mediated vesicle fusion requires the formation of PI(3,5)P2 to deliver vesicles and their cargo to the degradative environment of the lysosome.

molecular biology↗