Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder.

BACKGROUND: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD. METHODS: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD. RESULTS: We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity. LIMITATIONS: Cross-sectional designs cannot be used to infer causality. CONCLUSION: Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus. CLINICAL TRIAL REGISTRATION: ChiCTR2300078193.

Effects of childhood maltreatment and major depressive disorder on functional connectivity in hippocampal subregions.

Major Depressive Disorder (MDD) with childhood maltreatment is a prevalent clinical phenotype. Prior studies have observed abnormal hippocampal activity in MDD patients, considering the hippocampus as a single nucleus. However, there is limited research investigating the static and dynamic changes in hippocampal subregion functional connectivity (FC) in MDD patients with childhood maltreatment. Therefore, we employed static and dynamic FC analyses using hippocampal subregions, including the anterior hippocampus and posterior hippocampus, as seed regions to investigate the neurobiological alterations associated with MDD resulting from childhood maltreatment. This study involved four groups: MDD with (n = 48) and without childhood maltreatment (n = 30), as well as healthy controls with (n = 57) and without (n = 46) childhood maltreatment. Compared to MDD patients without childhood maltreatment, those with childhood maltreatment exhibit altered FC between the hippocampal subregion and multiple brain regions, including the anterior cingulate gyrus, superior frontal gyrus, putamen, calcarine gyrus, superior temporal gyrus, angular gyrus, and supplementary motor area. Additionally, dynamic FC between the right medial-2 hippocampal head and the right calcarine gyrus shows a positive correlation with childhood maltreatment across all its subtypes. Moreover, dFC between the right hippocampal tail and the left angular gyrus moderates the relationship between childhood maltreatment and the depression severity. Our findings of distinct FC patterns within hippocampal subregions provide new clues for understanding the neurobiological basis of MDD with childhood maltreatment.

The role of the thalamic subregions in major depressive disorder with childhood maltreatment: Evidences from dynamic and static functional connectivity.

BACKGROUND: Major depressive disorder (MDD) with a history of childhood maltreatment represents a highly prevalent clinical phenotype. Previous studies have demonstrated functional alterations of the thalamus among MDD. However, no study has investigated the static and dynamic changes in functional connectivity (FC) within thalamic subregions among MDD with childhood maltreatment. METHODS: This study included four groups: MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). Sixteen thalamic subregions were selected as seed to investigate group-differences in dynamic FC (dFC) and static FC (sFC). Correlation analyses were performed to assess the associations between abnormal FC and maltreatment severity. Eventually, moderation analyses were employed to explore the moderating role of abnormal FC in the relationship between maltreatment and depressive severity. RESULTS: MDD with childhood maltreatment exhibit abnormal thalamic subregions FC compared to MDD without childhood maltreatment, characterized by abnormalities with the sFC of the rostral anterior cingulate cortex, with the dFC of the calcarine, middle cingulate cortex, precuneus cortex and superior temporal gyrus. Furthermore, sFC with the rostral anterior cingulate cortex and dFC with the middle cingulate cortex were correlated with the severity of maltreatment. Additionally, dFC with the superior temporal gyrus moderates the relationship between maltreatment and depression severity. LIMITATIONS: The cross-sectional designs fail to infer causality. CONCLUSIONS: Our findings support thalamic dysfunction as neurobiological features of childhood maltreatment as well as vulnerability to MDD.

Recurrence of Henoch Schoenlein Purpura Nephritis in Children: A Retrospective Study.

The aim of the study was to identify predictive patient characteristics for Henoch Schoenlein Purpura (HSPN) relapse in childhood HSPN. One hundred and thirty-five Chinese children with HSPN were enrolled in this study, mean age 10.25 ± 3.39 years. The pathology of HSPN was according to the International Study of Kidney Disease in Children criteria.(ISKDC); ISKDC II(mesangial proliferation (MP)) AND ISKDC III (MP with <50 % crescents).Recurrence of HSPN was observed in 66.3 % patients; male to female ratio (2:1)Statistically significant correlation existed between biopsy grade(p < 0.001), gender(p < 0.001),age ranges(p = 0.002) and treatment regimen (p < 0.001)in the frequency of recurrent HSPN episodes. We identified some significant predictors for HSPN relapse such as the severity of HSPN, adjunctive therapies administered to these patients,and close attention should be paid in patients between the ages 7 and 12 years old. In addition, the use of mycophenolate mofetil as an adjunctive therapy in the treatment of HSPN may reduce the frequency of HSPN relapse episodes in children.

Effects of childhood neglect on regional brain activity and corresponding functional connectivity in major depressive disorder and healthy people: Risk factor or resilience?

BACKGROUND: Childhood neglect is a high risk factor for major depressive disorder (MDD). However, the effects of childhood neglect on regional brain activity and corresponding functional connectivity in MDD patients and healthy populations remains unclear. METHODS: Regional homogeneity, amplitude of low-frequency fluctuations (ALFF), fractional ALFF, degree centrality, and voxel-mirrored homotopic connectivity were extensively calculated to explore intraregional brain activity in MDD patients with childhood neglect and in healthy populations with childhood neglect. Functional connectivity analysis was then performed using regions showing abnormal brain activity in regional homogeneity/ALFF/fractional ALFF/degree centrality/voxel-mirrored homotopic connectivity analysis as seed. Partial correlation analysis and moderating effect analysis were used to explore the relationship between childhood neglect, abnormal brain activity, and MDD severity. RESULTS: We found decreased brain function in the inferior parietal lobe and cuneus in MDD patients with childhood neglect. In addition, we detected that childhood neglect was significant associated with abnormal cuneus brain activity in MDD patients and that abnormal cuneus brain activity moderated the relationship between childhood neglect and MDD severity. In contrast, higher brain function was observed in the inferior parietal lobe and cuneus in healthy populations with childhood neglect. CONCLUSIONS: Our results provide new evidence for the identification of neural biomarkers in MDD patients with childhood neglect. More importantly, we identify brain activity characteristics of resilience in healthy populations with childhood neglect, providing more clues to identify neurobiological markers of resilience to depression after suffering childhood neglect.

Cortical thickness and curvature abnormalities in patients with major depressive disorder with childhood maltreatment: Neural markers of vulnerability?

BACKGROUND: Childhood maltreatment has been related to various disadvantageous lifetime outcomes. However, the brain structural alterations that occur in major depressive disorder (MDD) patients with childhood maltreatment are incompletely investigated. METHODS: We extensively explored the cortical abnormalities including cortical volume, surface area, thickness, sulcal depth, and curvature in maltreated MDD patients. Twoway ANOVA was performed to distinguish the effects of childhood maltreatment and depression on structural abnormalities. Partial correlation analysis was performed to explore the relationship between childhood maltreatment and cortical abnormalities. Moreover, we plotted the receiver operating characteristic curve to examine whether the observed cortical abnormalities could be used as neuro biomarkers to identify maltreated MDD patients. RESULTS: We reach the following findings: (i) relative to MDD without childhood maltreatment, MDD patients with childhood maltreatment existed increased cortical curvature in inferior frontal gyrus; (ii) compared to HC without childhood maltreatment, decreased cortical thickness was observed in anterior cingulate cortex and medial prefrontal cortex in MDD patients with childhood maltreatment; (iii) we confirmed the inseparable relationship between cortical curvature alterations in inferior frontal gyrus as well as childhood maltreatment; (iv) cortical curvature abnormality in inferior frontal gyrus could be applied as neural biomarker for clinical identification of MDD patients with childhood maltreatment. CONCLUSIONS: Childhood maltreatment have a significant effects on cortical thickness and curvature abnormalities involved in inferior frontal gyrus, anterior cingulate cortex and medial prefrontal cortex, constituting the vulnerability to depression.

Aberrant static and dynamic functional connectivity of amygdala subregions in patients with major depressive disorder and childhood maltreatment.

Major depressive disorder (MDD) with childhood maltreatment is a heterogeneous clinical phenotype of depression with prominent features of brain disconnectivity in areas linked to maltreatment-related emotion processing (e.g., the amygdala). However, static and dynamic alterations of functional connectivity in amygdala subregions have not been investigated in MDD with childhood maltreatment. Here, we explored whether amygdala subregions (i.e., medial amygdala [MeA] and lateral amygdala [LA]) exhibited static functional connectivity (sFC) and dynamic functional connectivity (dFC) disruption, and whether these disruptions were related to childhood maltreatment. We compared sFC and dFC patterns in MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). The bilateral MeA and LA were selected as the seeds in the FC analysis. The results revealed a functional connectivity disruption pattern in maltreated MDD patients, characterized by sFC and dFC abnormalities involving the MeA, LA, and theory of mind-related brain areas including the middle occipital area, middle frontal gyrus, superior medial frontal gyrus, angular gyrus, supplementary motor areas, middle temporal gyrus, middle cingulate gyrus, and calcarine gyrus. Significant correlations were detected between impaired dFC patterns and childhood maltreatment. Furthermore, the dFC disruption pattern served as a moderator in the relationship between sexual abuse and depression severity. Our findings revealed neurobiological features of childhood maltreatment, providing new evidence regarding vulnerability to psychiatric disorders.

[Research progress on the correlation between sarcopenia and osteoarthritis].

Objective: To review the research progress on the correlation between sarcopenia and osteoarthritis (OA). Methods: The basic and clinical studies at home and abroad in recent years on sarcopenia and OA were extensively reviewed. The correlation between sarcopenia and OA was analyzed and summarized from five aspects: epidemiological status, risk factors, pathogenesis, clinical treatments, and the impact on joint arthroplasty. Results: Sarcopenia and OA are common diseases in the elderly with high prevalence and can increase the ill risk of each other. They share a set of risk factors, and show negative interactive and influence on pathogenesis and clinical treatments, thus participating in each other's disease process and reducing the treatment benefits. Clinical studies show that sarcopenia can affect the rehabilitation effect and increase the risk of postoperative complications after total joint arthroplasty in many ways. Conclusion: Current research results show that sarcopenia and OA are related and can be mutually affected in the above 5 aspects, but more studies are needed to further clarify the relationship between them, so as to provide more theoretical basis for the understanding, prevention, diagnosis, and treatments of the two diseases.

Intrinsic brain abnormalities in female major depressive disorder patients with childhood trauma: A resting-state functional magnetic resonance imaging study.

Objective: Childhood trauma is a strong predictor of major depressive disorder (MDD). Women are more likely to develop MDD than men. However, the neural basis of female MDD patients with childhood trauma remains unclear. We aimed to identify the specific brain regions that are associated with female MDD patients with childhood trauma. Methods: We recruited 16 female MDD patients with childhood trauma, 16 female MDD patients without childhood trauma, and 20 age- and education level-matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging (MRI). Regional brain activity was evaluated as the amplitude of low-frequency fluctuation (ALFF). Furthermore, functional connectivity (FC) analyses were performed on areas with altered ALFF to explore alterations in FC patterns. Results: There was increased ALFF in the left middle frontal gyrus (MFG) and the right postcentral gyrus (PoCG) in MDD with childhood trauma compared with MDD without childhood trauma. The areas with significant ALFF discrepancies were selected as seeds for the FC analyses. There was increased FC between the left MFG and the bilateral putamen gyrus. Moreover, ALFF values were correlated with childhood trauma severity. Conclusion: Our findings revealed abnormal intrinsic brain activity and FC patterns in female MDD patients with childhood trauma, which provides new possibilities for exploring the pathophysiology of this disorder in women.

Aberrant brain connectivity is associated with childhood maltreatment in individuals with major depressive disorder.

Although childhood maltreatment confers a high risk for the development of major depressive disorder, the neurobiological mechanisms underlying this connection remain unknown. The present study sought to identify the specific resting-state networks associated with childhood maltreatment. We recruited major depressive disorder patients with and without a history of childhood maltreatment (n = 31 and n = 30, respectively) and healthy subjects (n = 80). We used independent component analysis to compute inter- and intra- network connectivity. We found that individuals with major depressive disorder and childhood maltreatment could be characterized by the following network disconnectivity model relative to healthy subjects: (i) decreased intra-network connectivity in the left frontoparietal network and increased intra-network connectivity in the right frontoparietal network, (ii) decreased inter-network connectivity in the posterior default mode network-auditory network, posterior default mode network-limbic system, posterior default mode network-anterior default mode network, auditory network-medial visual network, lateral visual network - medial visual network, medial visual network-sensorimotor network, medial visual network - anterior default mode network, occipital pole visual network-dorsal attention network, and posterior default mode network-anterior default mode network, and (iii) increased inter-network connectivity in the sensorimotor network-ventral attention network, and dorsal attention network-ventral attention network. Moreover, we found significant correlations between the severity of childhood maltreatment and the intra-network connectivity of the frontoparietal network. Our study demonstrated that childhood maltreatment is integrally associated with aberrant network architecture in patients with major depressive disorder.

Altered Variability and Concordance of Dynamic Resting-State Functional Magnetic Resonance Imaging Indices in Patients With Major Depressive Disorder and Childhood Trauma.

Childhood trauma is a non-specific risk factor for major depressive disorder (MDD). resting-state functional magnetic resonance imaging (R-fMRI) studies have demonstrated changes in regional brain activity in patients with MDD who experienced childhood trauma. However, previous studies have mainly focused on static characteristics of regional brain activity. This study aimed to determine the specific brain regions associated with MDD with childhood trauma by performing temporal dynamic analysis of R-fMRI data in three groups of patients: patients with childhood trauma-associated MDD (n = 48), patients without childhood trauma-associated MDD (n = 30), and healthy controls (n = 103). Dynamics and concordance of R-fMRI indices were calculated and analyzed. In patients with childhood trauma-associated MDD, a lower dynamic amplitude of low-frequency fluctuations was found in the left lingual gyrus, whereas a lower dynamic degree of centrality was observed in the right lingual gyrus and right calcarine cortex. Patients with childhood trauma-associated MDD showed a lower voxel-wise concordance in the left middle temporal and bilateral calcarine cortices. Moreover, group differences (depressed or not) significantly moderated the relationship between voxel-wise concordance in the right calcarine cortex and childhood trauma history. Overall, patients with childhood trauma-associated MDD demonstrated aberrant variability and concordance in intrinsic brain activity. These aberrances may be an underlying neurobiological mechanism that explains MDD from the perspective of temporal dynamics.

Changes in Retinal Vessel Flow after Small Incision Lenticule Extraction.

Objective: In order to analyze changes in retinal vessel flow after small incision lenticule extraction (SMILE). Methods: A total of 32 patients (62 eyes) who underwent SMILE were enrolled in this prospective study. Optical parameters, including vessel density (VD), and perfusion density (PD) of foveal, parafoveal, and perifoveal regions, respectively, were measured before surgery and at 1 day, 1 week, 1 month, and 3 months postoperation. Preoperative parameters and surgical parameters were recorded. Results: Significant decreases in VD and PD on postoperative day 1 were detected in all quadrants, both in 3 mm and in 6 mm regions (P < 0.001). One month after surgery, VD returned to preoperative levels. None of the preoperative and surgical parameters were significantly correlated with the VD and PD fluctuations (all P > 0.05). Conclusion. VD may decrease significantly with regional disparity 1 day after SMILE while recovering at 1 month. Elevation of intraocular pressure due to suction may account for such changes.

Altered regional brain activity and functional connectivity patterns in major depressive disorder: A function of childhood trauma or diagnosis?

Childhood trauma (CT) is a non-specific risk factor for major depressive disorder (MDD). However, the neurobiological mechanisms of MDD with CT remain unclear. In the present study, we sought to determine the specific brain regions associated with CT and MDD etiology. Fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) analyses were performed to assess alterations of intrinsic brain activity in MDD with CT, MDD without CT, healthy controls with CT, and healthy controls without CT. Two-by-two factorial analyses were performed to examine the effects of the factors "MDD" and "CT" on fALFF and FC. Moderator analysis was used to explore whether the severity of depression moderated the relationship between CT and aberrant fALFF. We found that the etiological effects of MDD and CT exhibited negative impacts on brain dysfunction including altered fALFF in the left postcentral gyrus, left lingual gyrus, left paracentral lobule (PCL), and left cuneus. Decreased FC was observed in the following regions: (i) the left lingual gyrus seed and the left fusiform gyrus as well as the right calcarine cortex; (ii) the left PCL seed and the left supplementary motor area, left calcarine cortex, left precentral gyrus, and right cuneus; (iii) the left postcentral gyrus seed and left superior parietal lobule, right postcentral gyrus, and left precentral gyrus. Furthermore, the severity of depression acted as a moderator in the relationship between CT and aberrant fALFF in the left PCL. These data indicate that MDD patients with and without trauma exposure are clinically and neurobiologically distinct.

Covariation between spontaneous neural activity in the insula and affective temperaments is related to sleep disturbance in individuals with major depressive disorder.

BACKGROUND: Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions. METHODS: Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions. RESULTS: A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular-dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients. CONCLUSIONS: The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.

Covariation between Childhood-Trauma Related Resting-State Functional Connectivity and Affective Temperaments is Impaired in Individuals with Major Depressive Disorder.

Affective temperaments and childhood-trauma experiences are associated with major depressive disorder (MDD). So far, how the covariation between distinct affective temperaments and childhood-trauma insulted brain functional connectivities (FCs) contribute to MDD remains unclear. Here, we aimed to investigate whether certain brain FC patterns are related to certain affective temperaments and whether the FCs contribute to depressive symptom dimensions of MDD patients. Twenty-nine medication-free MDD patients and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Two multivariate analyses of partial least squares (PLS) regression were used to explore the associations among childhood-trauma related resting-state FCs, affective temperaments and depressive symptom dimensions. In all participants, a linear combination of 81 FCs (involving parahippocampus, amygdala, cingulate cortex, insula, frontal-temporal-parietal-occipital cortex, pallidum, and cerebellum) were associated with a linear combination of increased depressive, irritable, anxious, and cyclothymic temperaments. Moreover, the covariation between the PLS FC profile and the PLS affective-temperament profile were enhanced in the MDD patients compared to healthy controls. In MDD participants alone, the affective-temperament modulated FC profile (mainly of the lingual and temporal cortex) was associated with the somatization symptom dimension when age, sex, ill-duration, age-of-onset, and HARS scores were adjusted. The findings imply possible neural correlates of affective temperaments and may find applications in intervention of the somatization-depression symptoms by stimulation of the related neural correlates.

Aspirin-Triggered Lipoxin Protects Lipopolysaccharide-Induced Acute Kidney Injury via the TLR4/MyD88/NF-κB Pathway.

The protective effect of aspirin-triggered lipoxin (ATL) on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanisms were explored. To induce acute renal injury, mice were treated with LPS. Concentration of serum creatinine (SCr) and blood urea nitrogen (BUN) was detected, and inflammatory cytokines and AKI biomarkers were determined by ELISA. The relative protein expression levels of TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB signal pathway was assessed by Western blot. Mice subjected to LPS (4 mg/kg) treatment exhibited AKI demonstrated by markedly increased SCr and BUN levels compared with controls (P <0.01). Treatment with ATL decreased SCr and BUN levels after LPS injection (P <0.01). AKI biomarkers, such as urine NGAL, KIM-1, netrin-1, and L-FABP levels, increased by LPS and were inhibited by ATL (P <0.01). ATL also reduced LPS-induced secretion of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, and IL-8 (P <0.01). Furthermore, mice pretreated with ATL before exposure to LPS showed a reduction in TLR, MyD88, and p65 phosphorylation (P <0.01), which are the key factors of the TLR/MyD88/NF-κB signaling pathway. These results indicated that ATL had protective effects on renal function and showed amelioration of LPS-induced kidney injury. The mechanisms underlying the protective effects of ATL can be considered are related to attenuation of the TLR4/MyD88/NF-κB signaling pathway.

Amplitude of Low-Frequency Oscillations in Major Depressive Disorder With Childhood Trauma.

Major Depressive Disorder (MDD) with childhood trauma is one of the functional subtypes of depression. Frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) have been reported in MDD patients. However, there are few studies on ALFF about MDD with childhood trauma. Resting-state functional magnetic resonance imaging was used to measure the ALFF in 69 MDD patients with childhood trauma (28.7 ± 9.6 years) and 30 healthy subjects (28.12 ± 4.41 years). Two frequency bands (slow-5: 0.010-0.027 Hz; slow-4: 0.027-0.073 Hz) were analyzed. Compared with controls, the MDD with childhood trauma had decreased ALFF in left S1 (Primary somatosensory cortex), and increased ALFF in left insula. More importantly, significant group × frequency interactions were found in right dorsal anterior cingulate cortex (dACC). Our finding may provide insights into the pathophysiology of MDD with childhood trauma.

IVIG Delays Onset in a Mouse Model of Gerstmann-Sträussler-Scheinker Disease.

Our previous studies showed that intravenous immunoglobulin (IVIG) contained anti-Aß autoantibodies that might be able to treat Alzheimer's disease (AD). Recently, we identified and characterized naturally occurring autoantibodies against PrP from IVIG. Although autoantibodies in IVIG blocked PrP fibril formation and PrP neurotoxicity in vitro, it remained unknown whether IVIG could reduce amyloid plaque pathology in vivo and be used to effectively treat animals with prion diseases. In this study, we used Gerstmann-Sträussler-Scheinker (GSS)-Tg (PrP-A116V) transgenic mice to test IVIG efficacy since amyloid plaque formation played an important role in GSS pathogenesis. Here, we provided strong evidence that demonstrates how IVIG could significantly delay disease onset, elongate survival, and improve clinical phenotype in Tg (PrP-A116V) mice. Additionally, in treated animals, IVIG could markedly inhibit PrP amyloid plaque formation and attenuate neuronal apoptosis at the age of 120 days in mice. Our results indicate that IVIG may be a potential, effective therapeutic treatment for GSS and other prion diseases.

Cortical Gray Matter Loss, Augmented Vulnerability to Speech-on-Speech Masking, and Delusion in People With Schizophrenia.

People with schizophrenia exhibit impairments in target-speech recognition (TSR) against multiple-talker-induced informational speech masking. Up to date, the underlying neural mechanisms and its relationships with psychotic symptoms remain largely unknown. This study aimed to investigate whether the schizophrenia-associated TSR impairment contribute to certain psychotic symptoms by sharing underlying alternations in cortical gray-matter volume (GMV) with the psychotic symptoms. Participants with schizophrenia (N = 34) and their matched healthy controls (N = 29) were tested for TSR against a two-talker-speech masker. Psychotic symptoms of participants with schizophrenia were evaluated using the Positive and Negative Syndrome Scale. The regional GMV across various cortical regions was assessed using the voxel-based morphometry. The results of partial-correlation and mediation analyses showed that in participants with schizophrenia, the TSR was negatively correlated with the delusion severity, but positively with the GMV in the bilateral superior/middle temporal cortex, bilateral insular, left medial orbital frontal gyrus, left Rolandic operculum, left mid-cingulate cortex, left posterior fusiform, and left cerebellum. Moreover, the association between GMV and delusion was based on the mediating role played by the TSR performance. Thus, in people with schizophrenia, both delusions and the augmented vulnerability of TSR to informational masking are associated with each other and share the underlying cortical GMV reduction, suggesting that the origin of delusion in schizophrenia may be related to disorganized or limited informational processing (e.g., the incapability of adequately filtering information from multiple sources at the perceptual level). The TSR impairment can be a potential marker for predicting delusion severity.

Investigation into local white matter abnormality in emotional processing and sensorimotor areas using an automatically annotated fiber clustering in major depressive disorder.

This work presents an automatically annotated fiber cluster (AAFC) method to enable identification of anatomically meaningful white matter structures from the whole brain tractography. The proposed method consists of 1) a study-specific whole brain white matter parcellation using a well-established data-driven groupwise fiber clustering pipeline to segment tractography into multiple fiber clusters, and 2) a novel cluster annotation method to automatically assign an anatomical tract annotation to each fiber cluster by employing cortical parcellation information across multiple subjects. The novelty of the AAFC method is that it leverages group-wise information about the fiber clusters, including their fiber geometry and cortical terminations, to compute a tract anatomical label for each cluster in an automated fashion. We demonstrate the proposed AAFC method in an application of investigating white matter abnormality in emotional processing and sensorimotor areas in major depressive disorder (MDD). Seven tracts of interest related to emotional processing and sensorimotor functions are automatically identified using the proposed AAFC method as well as a comparable method that uses a cortical parcellation alone. Experimental results indicate that our proposed method is more consistent in identifying the tracts across subjects and across hemispheres in terms of the number of fibers. In addition, we perform a between-group statistical analysis in 31 MDD patients and 62 healthy subjects on the identified tracts using our AAFC method. We find statistical differences in diffusion measures in local regions within a fiber tract (e.g. 4 fiber clusters within the identified left hemisphere cingulum bundle (consisting of 14 clusters) are significantly different between the two groups), suggesting the ability of our method in identifying potential abnormality specific to subdivisions of a white matter structure.