Background Major depressive disorder (MDD) and nonsuicidal self-injury (NSSI) are both characterized by emotion regulation (ER) deficits, yet the pathophysiological mechanisms underlying comorbid presentations remain unclear. The aim of this investigation was to evaluate the ER abilities in patients with MDD and NSSI (MDD + NSSI) using ER questionnaires and electroencephalography (EEG), and to clarify their intrinsic connections with NSSI behaviors. Methods A total of 58 MDD + NSSI patients, 72 patients with MDD and without NSSI (MDD - NSSI), and 45 healthy controls (HCs) completed the ER questionnaires. A subgroup of 21 MDD + NSSI patients, 18 MDD - NSSI patients, and 20 HCs underwent task-based EEG to measure late positive potential (LPP) during cognitive reappraisal. Group differences and potential associations of these indicators with NSSI behaviors were analyzed. Results Compared to MDD - NSSI patients and HCs, MDD + NSSI patients exhibited significantly reduced positive reappraisal ability, increased catastrophizing tendency, and significant difficulties in emotional acceptance, impulse control, and effective use of ER strategies. Moreover, task-based EEG indicated a significant impairment in LPP modulation during cognitive reappraisal in MDD + NSSI patients, and their difference waves were smaller than those of MDD - NSSI patients and HCs. No significant associations were observed between these indicators and NSSI behaviors. Limitations Small sample size, cross-sectional design, uncontrolled medication status, and limited ER strategies assessed. Conclusions MDD + NSSI patients demonstrate self-reported ER deficits and impaired capacity to alleviate negative emotions during ER tasks.

Background:Childhood trauma (CT) has been recognized as a risk factor contributing to clinical heterogeneity and adverse outcomes in bipolar disorder (BD). The neurobiological mechanisms linking CT and BD, particularly those involving the kynurenine pathway (KP) and cerebellar neuroplasticity, remain unclear. Methods:A total of 51 BD patients with CT (BD+CT), 47 BD patients without CT (BD+NCT), and 50 healthy controls (HCs) were recruited. Peripheral KP metabolites were measured, and a biophysical neurite orientation dispersion and density imaging (NODDI) model was performed to evaluate microstructural alterations in cerebellar gray matter. Mediation analysis was conducted to examine whether these biomarkers mediate the association between CT and clinical phenotypes in BD. Results:In the BD+CT group, picolinic acid (PIC) levels were significantly lower, and the gray matter orientation dispersion index (ODI) in left cerebellar lobule VIIB was significantly higher, compared to other groups. PIC levels positively correlated with age of onset but negatively with emotional neglect and sexual abuse, anxiety and somatization, and left lobule VIIB ODI. Additionally, left lobule VIIB ODI showed a positive correlation with anxiety and somatization. Exploratory path modeling indicated that sexual abuse was indirectly associated with greater anxiety/somatization severity via reduced PIC levels and increased left lobule VIIB ODI. Conclusions:In BD, CT exposure was associated with reduced PIC levels, altered gray matter microstructure in left cerebellar lobule VIIB, and more severe anxiety/somatization. These findings offer insights into mechanisms for BD with CT, though the exploratory path model could not adjust for medication and requires replication in medication-naïve samples.

Lipid droplet (LD) accumulation in microglia results in a dysfunctional and proinflammatory state after ischemic stroke and worsens neurological outcomes; yet how this accumulation is regulated remains unclear. Interferon regulatory factor 7 (IRF7) is an immune regulatory factor whose role in lipid metabolism and autophagy has been increasingly studied in peripheral tissues. However, the role of IRF7 in microglial lipophagy (a selective autophagic process that targets LDs) and poststroke functional recovery remains unexplored. In this study, using a mouse photothrombotic ischemia (PTI) model, we observed that microglia in the peri-infarct region displayed persistent lipophagy impairment and LD accumulation for up to 21 days. Reanalysis of the single-cell RNA sequencing (scRNA-seq) dataset revealed that an Irf7high microglial MG1 subcluster (disease-associated microglia) was significantly associated with autophagy and lipid metabolism poststroke. Furthermore, microglial Irf7 conditional knockout (Irf7 cKO) mice exhibited a significant rescue of lipophagy impairment and an alleviation of the ensuing LD accumulation in microglia, accompanied by enhanced synaptic plasticity and motor functional recovery during the subacute phase poststroke. Consistently, in the 15-month-old distal middle cerebral artery occlusion (dMCAO) model, Irf7 cKO mice also displayed similar improvements. Similar results were also observed in vitro. Mechanistically, Gnai2 was identified as a positively regulated transcriptional target of IRF7. In BV2 cells and primary microglia, Gnai2 knockdown mitigated lipopolysaccharide (LPS)-induced lipophagy impairment, thereby reducing LD accumulation. This treatment also increased the level of phosphatidylcholine (PC), a key lipid for stabilizing small LDs as well as promoting autophagosome formation and autophagic flux. Consistently, microglial Irf7 deletion or knockdown attenuated stroke- or LPS-induced PC reduction both in vivo and in vitro. Furthermore, exogenous supplementation with CDP-choline, an intermediate in PC synthesis, alleviated LD accumulation and lipophagy impairment, thereby improving motor function. Additionally, delayed administration of an inhibitor of stimulator of interferon genes (STING, an upstream target of IRF7) replicated the beneficial effects observed in Irf7 cKO mice, and its effects were not further enhanced by microglial Irf7 deletion. Taken together, these novel findings reveal that persistent impairment of microglial lipophagy is a key contributor to poststroke LD accumulation, and that IRF7 is involved in this process through direct transcriptional activation of Gnai2, which reduces the PC levels. Suppressing IRF7 with a STING inhibitor is a potential strategy for modulating microglial lipid metabolism and promoting functional recovery following stroke.

Graph-based white matter tractometry represents bundles as networks, preserving spatial topology that traditional along-tract profiles collapse. This enables the detection of distributed pathology patterns organized across connected regions. The field is at a critical juncture: methods are proliferating rapidly, but validation infrastructure lags. We systematically assess maturity across the analytical pipeline, from diffusion measurements through graph construction, detection models, clinical applications, and validation resources. Diffusion metrics measure water behavior rather than directly measuring tissue microstructure. Their biological interpretation relies on model assumptions that have been validated only in restricted contexts. Tractography provides spatial scaffolding with known limitations, and graph-construction choices encode implicit hypotheses about the organization of pathology but are often underspecified. Clinical studies demonstrate consistent group differences across disorders. Where controlled comparisons exist, graph methods show modest improvements over traditional approaches. However, comprehensive benchmarking against TBSS and AFQ is absent. Dedicated validation platforms for tractometry detection models do not yet exist. We document concrete barriers to systematic validation and assess emerging infrastructure addressing these gaps. Graph-based tractometry shows promise as a research tool. Realizing its clinical potential requires validation matching the maturity of traditional approaches.

Abstract Background Bipolar disorder (BIP) and obsessive-compulsive disorder (OCD) frequently co-occur and show evidence of genetic overlap, yet the specific pleiotropic loci and their functional mechanisms remain unclear. Methods We conducted large-scale genetic analyses using GWAS summary statistics for BIP and OCD, excluding 23andMe data. We applied conjunctional FDR analysis to identify pleiotropic variants jointly associated with BIP and OCD, followed by integrative annotation through transcriptomic (eQTL, sQTL), epigenomic (mQTL, haQTL), and proteomic (pQTL, histone PTM) data. SMR analysis was used to prioritize putative regulatory effects, while AlphaGenome predictions and targeted histone proteomics were employed to evaluate allele-specific chromatin changes. Results We observed a significant genetic correlation ( r g = 0.38, P = 3.8 × 10 -29 ) and extensive polygenic overlap between BIP and OCD. Bidirectional MR supported causal effects in both directions, with stronger evidence for BIP influencing OCD risk. ConjFDR analysis revealed 2,143 pleiotropic SNPs jointly associated with BIP and OCD, with convergent signals at the ITIH3/ITIH4 locus. Summary-data-based Mendelian randomization (SMR) and colocalization with multi-omic QTLs (eQTL, pQTL, mQTL, and haQTL) further prioritized the ITIH3/4 locus, where multiple SNPs (e.g., rs3774364) colocalized with H3K27ac histone acetylation QTLs in the prefrontal cortex (PP_H4 > 0.5). Integrated PBMC RNA-seq and complementary histone mass spectrometry linked immune–ECM transcriptional activity to exploratory global histone acetylation changes in BIP and OCS-BIP, with suggestive alterations in H3K27ac-containing peptides. Conclusions Our multi-omic analysis highlights ITIH3/ITIH4 as a prioritized pleiotropic locus for BIP and OCD. Epigenetic regulation, particularly through histone acetylation, may underlie shared susceptibility and offers a novel mechanistic link between these psychiatric disorders.

Background: Dysmenorrhea has been linked to alterations in brain structure, endocrine function, and reproductive outcomes; however, these associations have largely been examined in isolation. Whether menstrual pain influences reproductive success through an integrated neuroendocrine pathway remains unclear. Methods: We analyzed data from 1,264 women in the UK Biobank to investigate the relationship between menstrual pain and live birth. Diffusion MRI metrics were reduced using principal component analysis and evaluated via multivariate models to identify pain-related white matter alterations. Circulating hormonal and inflammatory markers were assessed, and structural equation modeling (SEM) was used to test hypothesized pathways linking menstrual pain, white matter microstructure, endocrine function, and live birth outcomes. Findings: Menstrual pain was associated with a lower likelihood of live birth and widespread alterations in white matter microstructure, particularly within the limbic pathway. These structural changes were significantly associated with elevated Prolactin (PRL) levels. SEM revealed that menstrual pain was linked to live birth both directly and indirectly through a neuroendocrine pathway involving white matter alterations and PRL dysregulation. Interpretation: Our findings provide population-level evidence that menstrual pain is associated with impaired reproductive outcomes through a neuroendocrine mechanism. White matter microstructure may serve as a key intermediary linking central pain processing to endocrine regulation and reproductive function, highlighting potential targets for early intervention.

Cognitive impairment in patients with major depressive disorder (MDD) and a history of childhood trauma (CT) may be associated with microstructural abnormalities in the neostriatum, including the caudate and putamen. However, the nature of these alterations and their role in cognitive dysfunction remain unclear. This study aimed to characterise neostriatal microstructural alterations and examine whether they mediate the association between CT and cognitive impairment in MDD. Multi-shell diffusion MRI data from 148 patients with MDD and 47 healthy controls (HCs) were analysed using free-water diffusion tensor imaging (FWDTI) and neurite orientation dispersion and density imaging (NODDI). CT and cognition were assessed using the Childhood Trauma Questionnaire and the MATRICS Consensus Cognitive Battery, respectively. Compared with HCs, MDD patients showed significantly higher tissue-corrected fractional anisotropy (FAt) in the bilateral caudate. CT severity was significantly positively correlated with FAt and intracellular volume fraction, while significantly negatively correlated with neurite orientation dispersion (OD) in the neostriatum. Mediation analysis further showed that OD and FAt in the right putamen partially mediated the association between CT and cognitive impairment. These findings suggest that the neostriatum may represent a key neurobiological substrate linking CT to cognitive dysfunction in MDD and support the utility of advanced diffusion MRI metrics for characterising trauma-related microstructural alterations.

Patients with major depressive disorder commonly exhibit varying degrees of social dysfunction, whose pathological mechanisms may be closely associated with abnormalities in the social reward system.In recent years, research on social reward circuitry has shifted from a focus on localized functional deficits to a systematic perspective of dysregulation across multiple brain regions. Using multimodal neuroimaging and computational modeling approaches, researchers have begun to explore the dynamic interaction patterns between large-scale brain networks and reward circuitry across the three phases of anticipation, consumption, and learning, as well as emerging topics such as circuit-targeted neuromodulation.This review systematically summarizes the functional abnormalities in the social reward circuitry of patients with major depressive disorder, exploring the potential dual mechanisms involving localized functional impairments of key brain regions and network-level dysregulation across three distinct phases of reward processing: anticipation, consumption, and learning, and elaborates the dynamic manifestation of a dual-mechanism model of local brain region functional impairment-network coordination dysregulation during these phases. The review may provide theoretical foundations for understanding the neural substrates underlying social dysfunction in depression and for optimizing clinical treatment strategies, such as precise neuromodulation targeting specific phases or specific circuits.

Importance:Depression is a significant global public health issue, with somatic symptoms being a common and challenging aspect of its management. Objective:This study aimed to evaluate the efficacy and safety of toludesvenlafaxine hydrochloride sustained-release tablets (Roxylin®) for somatic symptoms of major depressive disorder (MDD). Design Setting and Participants:Prospective, single-arm, multicenter clinical study conducted between June 1, 2023 and May 1, 2024, enrolling patients diagnosed with MDD with somatic symptoms at four hospitals across China. Intervention:All participants received toludesvenlafaxine hydrochloride monotherapy for 8 weeks. Main Outcomes and Measures:The primary outcomes were improvements in somatic depression symptoms measured by PHQ-15 and SSS-CN at baseline and weeks 2, 4, and 8, while secondary outcomes included changes in depressive symptoms (HAMD-17), pain intensity (VAS), fatigue (MFI-20), and functional impairment (SDS), with adverse events monitored. Results:Out of 72 screened patients, 61 were enrolled. The mean age of the participants was 30.1 ± 9.0 years, ranging from 18 to 53 years, with 29.6% being male and 70.4% female. After 8 weeks of treatment, significant reductions were observed in PHQ-15 scores (-5.8 ± 4.4, P < 0.001) and SSS-CN scores (-12.8 ± 10.3, P < 0.001), indicating improvement in somatic symptoms. Secondary outcomes also showed significant improvements in depressive symptoms (HAMD-17: -15.3 ± 7.4, P < 0.001), pain intensity (VAS: -1.97 ± 2.44, P < 0.001), fatigue (MFI-20: -12.8 ± 14.1, P < 0.001), and functional disability (SDS: -8.3 ± 6.5, P < 0.001). The occurrence of adverse events was 52.5%, with no serious adverse events reported. Conclusion:Toludesvenlafaxine hydrochloride significantly improved somatic symptoms in patients with MDD and somatic symptoms, with a favorable safety profile, supporting its use as an effective treatment option. Clinicaltrialsgov Identifier:NCT05849272.

Background: Major depressive disorder (MDD) encompasses a broad spectrum of heterogeneous symptoms arising from distinct etiological mechanisms. Phenotypic markers of psychopathology are most likely influenced by exposure to childhood maltreatment, yielding distinct subtypes within conventional diagnostic boundaries. However, the biological interactions between MDD subtypes and types of childhood trauma remain unclear. Methods: 50 atypical depression (AD) patients, 97 non-AD patients and 50 healthy controls were included to complete multi-shell diffusion MRI scans and clinical assessments. Differential tractography was performed to clarify the axonal injury between the AD and non-AD groups. Moreover, correlational tractography was employed to individually assess the relationship between quantitative anisotropy (QA) and all types of childhood trauma in each depressed subgroup. Results: Our study found that AD and non-AD patients had differential axonal loss primarily involving the bilateral superior longitudinal fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, parietal aslant tract, and corpus callosum. Furthermore, AD patients showed significantly negative associations between QA values, childhood trauma total scores, and threat-related adversity, while significantly positive associations were observed in non-AD patients. However, similar phenomena were not observed for deprivation-related adversities. Discussion: Our findings indicate differential spatial patterns of axonal alterations associated with threat-related adversity in atypical depression and non-atypical depression. Efforts to attenuate the consequences of childhood maltreatment for MDD should consider the associations between specific patterns of adversity and specific clinical manifestations.

BACKGROUND:The heterogeneity of symptoms in major depressive disorder is impeding progress toward patient-specific treatment strategies and course trajectories. Origins of such differential clinical manifestations likely have dissociable pathophysiologies, but neural substrates associated with specific atypical depressive symptoms remain elusive. METHODS:The muti-shell diffusion MRI images were acquired from 50 patients with atypical depression (AD), 97 patients with non-atypical depression (non-AD), and 50 healthy controls (HCs). We used gray matter-specific multi-compartment diffusion models (cortical-neurite orientation dispersion and density imaging and free-water elimination model) to assess abnormalities of gray matter microstructure associated with AD. Superficial U-fibers analysis was performed to clarify short-range cortico-cortical connections. RESULTS:Abnormalities in intracellular volume fraction (ICVF) and free-water fraction anisotropy were found in the superior frontal gyrus, middle frontal gyrus, inferior parietal gyrus, and superior parietal gyrus across three groups. Post-hoc pairwise comparative analysis yielded similar results. While adjusting for the effects of age, gender, education, and the ICVF mentioned above, AD patients showed significantly higher scores in reversed neurovegetative symptoms and leaden paralysis compared with non-AD patients. Moreover, diagnosis-related alterations in ICVF of right caudal middle frontal gyrus and education-related changes in ICVF of right superior frontal gyrus were significantly associated with hypersomnia. We also found that underlying superficial U-fibers reflected deficits in cortical-derived neurite density. CONCLUSIONS:Cortical-derived neurite density abnormalities were significantly associated with atypical depressive symptoms, capturing interindividual etiological heterogeneity in patients with major depressive disorder. Cortical-derived neurite density within the medial prefrontal gyrus may be a robust biomarker for atypical depressive symptoms of AD.

To the editor: Non-suicidal self-injury(NSSI)is an array of directly prepense or repetitive self-harm behaviours without suicidal intent.Indi-viduals engage in self-injurious behaviours to reduce negative mental and cognitive states or evoke positive emotions.1 Emotion regulation(ER),the capability to regulate and control emotional responses,is often compromised in NSSI individuals.2 Major depressive disorder(MDD)is characterised by severely and persistently depressed mood,so patients with MDD are very likely to use NSSI to alleviate negative feelings.There-fore,the clinical importance of studying ER among patients with MDD and NSSI cannot be overemphasised.

Depression is a serious mental disorder with complex etiology, exhibiting strong heterogeneity in clinical manifestations such as various subtypes. Research on depression subtypes may deepen the understanding of the disease, contributing to the diagnosis and prognosis. While brain functional network and graph neural networks (GNNs) provide such a means, the task is still challenged by limited feature encoding from the informative fMRI data, ineffective information fusion of brain functional network, and small size of the recruited subjects. Therefore, we propose a hierarchical encoding and fusion framework of brain functions. First, we pre-train a model to extract the features from individual brain regions, which signify nodes in the brain functional network. Then, distinct graphs are constructed to link the nodes within each subject, resulting in multi-view graphs of the brain functional network. We further develop a graph fusion strategy to integrate the multi-view information, by referring to the local encoding of the nodes and their interactions across multiple graph instances. Finally, we attain the classification of depression subtypes based on the fused graph representation. The experimental results demonstrate that our method can superiorly distinguish major depression subtypes and outperform the state-of-the-art methods.

Objective·To systematically review the effectiveness of actigraphy on the evaluation of circadian rhythm characteristics in patients with depression.Methods·A systematic literature search was conducted in PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CNKI,WanFang Data,and Chinese biomedical literature database(CBM),from the inception of each database to May 5th,2023.Case control studies that used actigraphy to evaluate circadian rhythms in patients with depression and compared them with healthy controls were collected.Literature was screened according to the inclusion and exclusion criteria,and the quality of the included literature was evaluated by using the Newcastle-Ottawa Scale.The meta-analysis was performed by using RevMan 5.4 software.Results·A total of 9 articles were included,including 390 patients with depression and 288 healthy controls.The meta-analysis showed that the MESOR(midline statistic of rhythm)(SMD=-0.29,95%CI-0.51 ?-0.07,P=0.009)of the circadian cosine function in patients with depression was lower than that in healthy controls;sleep onset(MD=33.06,95%CI 14.90 ? 51.23,P=0.000)and sleep offset(MD=53.80,95%CI 22.38 ? 85.23,P=0.000)were later in patients with depression than those in healthy controls;no statistical difference was found in the activity level of the most active 10 hours(SMD=-0.26,95%CI-0.52 ? 0.01,P=0.060)between patients with depression and healthy controls,although there was a trend for lower activity in patients with depression;no statistical difference was found in the acrophase(MD=25.33,95%CI-12.41 ? 63.06,P=0.190)of the circadian cosine function between patients with depression and healthy controls;no clear statistical significance of the difference was found in the amplitude(SMD=-0.14,95%CI-0.42 ? 0.14,P=0.340)and the activity level of the least active 5 hours(SMD=0.31,95%CI-0.10 ? 0.71,P=0.140)between patients with depression and healthy controls.Conclusion·Actigraphy can reflect circadian rhythm disruption in patients with depression to some extent,but the limited number of included studies and inconsistencies in the study populations and methodologies have affected the quality and results of the analyses.More high-quality clinical trials are needed to provide evidence.

Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.

BACKGROUND:GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.METHODS:Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting.RESULTS:BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice.CONCLUSIONS:Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.

Resting-state fMRI (rs-fMRI) is an effective tool for quantifying functional connectivity (FC), which plays a crucial role in exploring various brain diseases. Due to the high dimensionality of fMRI data, FC is typically computed based on the region of interest (ROI), whose parcellation relies on a pre-defined atlas. However, utilizing the brain atlas poses several challenges including 1) subjective selection bias in choosing from various brain atlases, 2) parcellation of each subject's brain with the same atlas yet disregarding individual specificity; 3) lack of interaction between brain region parcellation and downstream ROI-based FC analysis. To address these limitations, we propose a novel randomizing strategy for generating brain function representation to facilitate neural disease diagnosis. Specifically, we randomly sample brain patches, thus avoiding ROI parcellations of the brain atlas. Then, we introduce a new brain function representation framework for the sampled patches. Each patch has its function description by referring to anchor patches, as well as the position description. Furthermore, we design an adaptive-selection-assisted Transformer network to optimize and integrate the function representations of all sampled patches within each brain for neural disease diagnosis. To validate our framework, we conduct extensive evaluations on three datasets, and the experimental results establish the effectiveness and generality of our proposed method, offering a promising avenue for advancing neural disease diagnosis beyond the confines of traditional atlas-based methods. Our code is available at https://github.com/mjliu2020/RandomFR.

IntroductionSymptoms during the onset of major depressive disorder [MDD] and bipolar disorder type II [BD-II] are similar. The difference of hippocampus subregion could be a biological marker to distinguish MDD from BD-II.MethodsWe recruited 61 drug-naïve patients with a first-episode MDD and BD-II episode and 30 healthy controls (HC) to participate in a magnetic resonance imaging [MRI] study. We built a general linear model (one-way analysis of covariance) with 22 hippocampal subfields and two total hippocampal volumes as dependent variables, and the diagnosis of MDD, BD-II, and HC as independent variables. We performed pair-wise comparisons of hippocampal subfield volumes between MDD and HC, BD-II and MDD, BD-II and HC with post hoc for primary analysis.ResultsWe identified three regions that differed significantly in size between patients and controls. The left hippocampal fissure, the hippocampal–amygdaloid transition area (HATA), and the right subiculum body were all significantly larger in patients with MDD compared with the HC. In the onset of first-episode of MDD, the hippocampal volume increased significantly, especially on the left side comparing to HC. However, we found differences between MDD and BD-II were not statistically significant. The volume of the left HATA and right subiculum body in BD-II was larger.ConclusionsThe sample size of this study is relatively small, as it is a cross-sectional comparative study. In both MDD and BD-II groups, the volume of more left subregions appeared to increase. The left subregions were severely injured in the development of depressive disorder.

Bipolar disorder, as a major mental illness, has a high lifetime suicide attempt rate in patients, and suicidal behavior is most likely to occur during depressive episodes. Therefore, in-depth study of its mechanism is essential for prevention, early detection and intervention of suicide. With the development of magnetic resonance imaging (MRI) technology, it has been found that there are abnormalities in the brain structure and function in suicidal patients with bipolar disorder. This article reviews the studies on suicide in bipolar disorder patients by MRI from four aspects: structure, function, structure-function, and central metabolism and cerebral blood flow perfusion, and summarizes the suicide-related changes. This review focuses on distinguishing the brain MRI changes under different mood states and diverse definitions of suicide, aiming to provide reference for further exploration of the pathophysiological mechanism of suicide in bipolar disorder.