Xiufeng Xu

Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: A voxel-based morphometry study

Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain.

Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Naïve Patients with Obsessive-Compulsive Disorder

Background Obsessive-compulsive disorder (OCD) is a mental illness characterized by the loss of control. Because the cingulate cortex is believed to be important in executive functions, such as inhibition, we used functional magnetic resonance imaging (fMRI) techniques to examine whether and how activity and functional connectivity (FC) of the cingulate cortex were altered in drug-naïve OCD patients. Methods Twenty-three medication-naïve OCD patients and 23 well-matched healthy controls received fMRI scans in a resting state. Functional connectivities of the anterior cingulate (ACC) and the posterior cingulate (PCC) to the whole brain were analyzed using correlation analyses based on regions of interest (ROI) identified by the fractional amplitude of low-frequency fluctuation (fALFF). Independent Component Analysis (ICA) was used to identify the resting-state sub-networks. Results fALFF analysis found that regional activity was increased in the ACC and decreased in the PCC in OCD patients when compared to controls. FC of the ACC and the PCC also showed different patterns. The ACC and the PCC were found to belong to different resting-state sub-networks in ICA analysis and showed abnormal FC, as well as contrasting correlations with the severity of OCD symptoms. Conclusions Activity of the ACC and the PCC were increased and decreased, respectively, in the medication-naïve OCD patients compared to controls. Different patterns in FC were also found between the ACC and the PCC with respect to these two groups. These findings implied that the cardinal feature of OCD, the loss of control, may be attributed to abnormal activities and FC of the ACC and the PCC.

White-matter volume reduction and the protective effect of immunosuppressive therapy in systemic lupus erythematosus patients with normal appearance by conventional magnetic resonance imaging.

Objective. The central nervous system (CNS) is often affected by systemic lupus erythematosus (SLE), but assessment of CNS outcomes using noninvasive cerebral structural measures remains in its infancy. Magnetic resonance imaging (MRI) with expert visual interpretation is critical to diagnosis, but does not permit quantitative measurements. Our pilot study investigated whether quantitative brain volumetric analyses could be used to detect white-matter (WM) abnormalities and responses to treatment in SLE (ClinicalTrials.gov: NCT00703742). Methods. Forty-two pairs of SLE patients and healthy controls underwent high-resolution 3-dimensional structural MRI scans. Combining voxel-based morphometry and region of interest analyses, subtle WM volume abnormalities in whole brains from SLE patients were identified, and regional WM volume was calculated. Associations between WM volume and symptom severity, as well as the effects of immunosuppressive therapy, were then investigated. Results. The WM volume of the SLE group was significantly decreased in the bilateral posterior and anterior crus of the internal capsule (PIC and AIC, respectively), the subgyral right frontal lobe, and left temporal lobe (p < 0.001). Regional WM volume (left PIC and right AIC) was correlated with SLEDAI scores. The WM volume of patients treated with immunosuppressive therapy was greater than that of patients who were never treated with immunosuppressive therapy. Conclusion. Quantitative brain volumetric analyses detect brain injuries in WM for SLE that are not obvious by conventional MRI, and may be adequately sensitive and quantitative to measure the effect of therapeutic interventions in preventing brain injury and outcomes in SLE.

Delineation of Early and Later Adult Onset Depression by Diffusion Tensor Imaging

Background Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD. Method In this study, 61 pairs of untreated, non-elderly, first-episode MDD patients and healthy controls (HCs) aged 18–45 years old received DTI scans. The voxel-based analysis method (VBM), classification analysis, using the Statistical Package for the Social Sciences (SPSS), and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms. Results Classification analysis suggested in the best model that there were two subgroups of MDD patients, delineated by an age of onset of 30 years old, by which MDD patients could be divided into EO (18–29 years old) and LO (30–45 years old) groups. LO MDD was characterized by decreased FA, especially in the white matter (WM) of the fronto-occipital fasciculus and posterior limb of internal capsule, with a negative correlation with the severity of depressive symptoms; in marked contrast, EO MDD showed increased FA, especially in the WM of the corpus callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms. Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms. This DTI study supported the evidence of an exact age for the delineation of MDD, which could have broad multidisciplinary importance. Trial Registration ClinicalTrials.gov NCT00703742

Abnormal regional homogeneity of drug-naïve obsessive-compulsive patients.

To explore the possible abnormal resting-state activity in patients with obsessive-compulsive disorder (OCD), the regional homogeneity (ReHo) of 22 pairs of patients and well-matched healthy controls was calculated. Compared with controls, the patients showed higher ReHo in the left anterior cingulate cortex, but lower ReHo in the left inferior temporal gyrus. These findings supported the abnormal resting-state brain activity in drug-naïve OCD patients. No significant correlations between ReHo value and four clinical characteristics were found, suggesting that abnormal ReHo might be trait-related in OCD.

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

Hypomethylation of the HTR1A promoter region and high expression of HTR1A in the peripheral blood lymphocytes of patients with systemic lupus erythematosus.

Abstract: The occurrence of systemic lupus erythematosus (SLE) involves a gene–environment interaction and epigenetic regulations, such as DNA methylation, may play important role in the etiology of SLE. Some neurotransmitters, such as serotonin, can regulate T- and B-cell proliferation via the 5-HT1A receptor and are involved in the pathology of SLE. The abnormal methylation of DNA has been reported in SLE, but there has been no study concerning the serotonin system. This study was conducted to explore the DNA methylation status of the promoter region of HTR1A (PR-HTR1A) and the level of HTR1A mRNA in the peripheral blood lymphocytes (PBLC) of SLE patients and healthy controls (HC). In this study, the DNA methylation status of PR-HTR1A and the level of HTR1A mRNA were detected in the PBLC of SLE patients and HC. The results showed significant hypomethylation of PR-HTR1A in SLE patients compared with HC. The patients also showed a significantly higher HTR1A mRNA level than did the controls. Relatively higher percentage of anti-histone antibodies in methylated SLE patients was found compared with unmethylated patients. Our results support the hypothesis that the hypomethylation of PR-HTR1A and overexpression of HTR1A might contribute to SLE. These results also reveal that epigenetic regulation via the serotonin system may contribute to SLE, and reveal the link between the brain and the immune system.

Changes of grey matter volume in first-episode drug-naive adult major depressive disorder patients with different age-onset.

Objective Little is known about the pathological mechanism of early adult onset depression (EOD) and later adult onset depression (LOD). We seek to determine whether grey matter volume (GMV) change in EOD and LOD are different, which could also delineate EOD and LOD. Methods In present study, 147 first-episode, drug-naive patients with major depressive disorder (MDD), age between 18 and 45, were divided into two groups on the basis of age of MDD onset: the early adult onset group (age 18–29) and the later adult onset group (age 30–44), and a total of 130 gender-, and age-, matched healthy controls (HC) were also divided into two groups which fit for each patient group. Magnetic resonance imaging was conducted on all subjects. The voxel-based morphometry (VBM) approach was employed to analyze the images. Results Widespread abnormalities of GMV throughout parietal, temporal, limbic regions, occipital cortex and cerebellum were observed in MDD patients. Compare to young HC, reduced GMV in right fusiform gyrus, right middle temporal gyrus, vermis III and increased GMV in right middle occipital gyrus were seen in the EOD group. In contrast, relative to old HC, decreased GMV in the right hippocampus and increased GMV in the left middle temporal gyrus were observed in the LOD group. Compared to the LOD group, the EOD group had smaller GMV in right posterior cingulate cortex. There was no significant correlation between GMV of the right posterior cingulate cortex and the score of the depression rating scale in patients group. Conclusions The GMV of the brain areas that were related to mood regulation was decreased in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different GMV changes relative to each age-matched comparison group, suggesting depressed adult patients with different age-onset might have different pathological mechanism.

Resting-state brain alteration after a single dose of SSRI administration predicts 8-week remission of patients with major depressive disorder

BACKGROUND The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment. METHOD Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement. RESULTS Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint. CONCLUSIONS This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings

Among individuals diagnosed with schizophrenia, approximately 20%–33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. control. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.