Search

Abstract Background Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

Background: Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods: We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results: At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions: The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that progressive supranuclear palsy (PSP) correlates with structural abnormalities in several distinct regions of the brain. However, whether there are changes in the morphological similarity network (MSN) and the relationship between changes in brain structure and gene expression remain largely unknown. Methods: We used two independent cohorts (discovery dataset: PSP: 51, healthy controls (HC): 82; replication dataset: PSP: 53, HC: 55) for MSN analysis and comparing the longitudinal changes in the MSN of PSP. Then, we applied partial least squares regression to determine the relationships between changes in MSN and spatial transcriptional features and identified specific genes associated with MSN differences in PSP. We further investigated the biological processes enriched in PSP‐associated genes and the cellular characteristics of these genes, and finally, we performed an exploratory analysis of the relationship between MSN changes and neurotransmitter receptors. Results: We found that the MSN in PSP patients was mainly decreased in the frontal and temporal cortex but increased in the occipital cortical region. This difference is replicable. In longitudinal studies, MSN differences are mainly manifested in the frontal and parietal regions. Furthermore, the expression pattern associated with MSN changes in PSP involves genes implicated in astrocytes and excitatory and inhibitory neurons and is functionally enriched in neuron‐specific biological processes related to synaptic signaling. Finally, we found that the changes in MSN were mainly negatively correlated with the levels of serotonin, norepinephrine, and opioid receptors. Conclusions: These results have enhanced our understanding of the microscale genetic and cellular mechanisms responsible for large‐scale morphological abnormalities in PSP patients, suggesting potential targets for future therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. Methods: We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. Results: Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. Conclusions: The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease. [ABSTRACT FROM AUTHOR]