Neural mechanism of non-adaptive cognitive emotion regulation in patients with non-suicidal self-injury.

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.

Transcriptional signal and cell specificity of genes related to cortical structural differences of post-traumatic stress disorder.

Due to the diversity of traumatic events, the diagnosis of Post-traumatic Stress Disorder is heterogeneous. The pathogenesis has been explored in the fields of brain imaging and genomics separately, but the results are inconsistent. Previous research evidenced that there existed structural differences between PTSD and healthy controls in multiple brain regions. This study further looked into the differences of brain structure in PTSD at the whole brain level and analyzed the difference-related genomes. The brain structure imaging data of 36 patients and 32 healthy controls were taken as morphological indexes. Partial least squares regression and transcriptome data were used to extract genomes related to structural differences. Additional data sets were used to study transcription characteristics of genome. Morphological differences were found in cingulate gyrus between patients and control group. Differentially expressed genes related to Morphometric similarity networks difference space were also observed. The obtained genes (i.e., RORA, PRKG1 and FKBP5) were proved to be related to the disorder with no significant correlation with other mental illnesses. In the subsequent cell type analysis, astrocytes, excitatory neurons and inhibitory neurons were evidenced to have the most significant correlation with these genes. This study found morphologically different brain regions related to PTSD. The related genome transcription analysis connects the structural differences and molecular mechanisms.

The disruption of functional connectome gradient revealing networks imbalance in pediatric bipolar disorder.

OBJECTIVE: Pediatric bipolar disorder (PBD) is a psychiatric disorder marked by alteration of brain networks. However, the understanding of these alterations in topological organization still unclear. This study aims to leverage the functional connectome gradient to examine changes in functional network hierarchy in PBD. METHOD: Connectome gradients were used to scrutinize the differences between functional gradient map in PBD patients (n = 68, aged 11 to 18) and healthy controls (HC, n = 37, aged 11 to 18). The association between regional altered gradient scores and clinical factors was examined. We further used Neurosynth to determine the correlation of the cognitive terms with the PBD principal gradient changes. RESULTS: Global topographic alterations were exhibited in the connectome gradient in PBD patients, involving gradient variance, explanation ratio, gradient range, and gradient dispersion in the principal gradient. Regionally, PBD patients revealed that the default mode network (DMN) held the most majority of the brain areas with higher gradient scores, whereas a higher proportion of brain regions with lower gradient scores in the sensorimotor network (SMN). These regional gradient differences exhibited significant correlation with clinical features and meta-analysis terms including cognitive behavior and sensory processing. CONCLUSION: Functional connectome gradient presents a thorough investigation of large-scale networks hierarchy in PBD patients. This exhibited excessive segregation between DMN and SMN supports the theory of imbalance in top-down control and bottom-up in PBD and provides a possible biomarker for diagnostic assessment.

Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder.

Background: Pediatric bipolar disorder (PBD) has been proven to be related to abnormal brain structural connectivity, but how the abnormalities in PBD correlate with gene expression is debated. Objective: This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD. Methods: Morphometric similarity networks (MSN) were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants (59 patients and 43 controls). Partial least squares (PLS) regression was used to calculate MSN differences related to transcriptomic data in AHBA. The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools. Results: MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants. MSN differences were spatially correlated with the PBD-related weighted genes. The weighted genes were enriched for "trans-synaptic signaling" and "regulation of ion transport", and showed significant specific expression in excitatory and inhibitory neurons. Conclusions: This study identified the genes that contributed to structural network aberrations in PBD. It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.