ngjiang Li

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

Different white matter abnormalities between the first-episode, treatment-naive patients with posttraumatic stress disorder and generalized anxiety disorder without comorbid conditions

BACKGROUND This study compared brain white matter integrity in two groups of patients with DSM-IV anxiety disorders. METHOD Seventeen patients with posttraumatic stress disorder (PTSD), 20 with generalized anxiety disorder (GAD), and 28 healthy controls were assessed on diffusion tensor imaging. RESULTS As compared to healthy controls, increased fractional anisotropy (FA) in left superior frontal gyrus in PTSD patients, and increased FA in right postcentral gyrus in GAD subjects were exhibited. Furthermore, patients with PTSD showed reduced FA in right anterior cingulate gyrus relative to GAD subjects. However, there was no significant correlation between the FA value of any altered region and the severity of PTSD or GAD. LIMITATIONS The sample studied can be considered small. Gender and educational level were not well-matched among the groups. CONCLUSIONS We tentatively speculate that abnormal white matter integrity of right anterior cingulate gyrus is an important neuroimaging marker of PTSD that distinguishes it from other anxiety disorders such as GAD.

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.

BackgroundWhite matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear.MethodsWe used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females).ResultsWe found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [−18 46–14]), left limbic lobe uncus (peak coordinates [−18 2–22]), and right cerebellum posterior lobe (peak coordinates [26–34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores.ConclusionsWe found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

High-frequency rTMS treatment increases white matter FA in the left middle frontal gyrus in young patients with treatment-resistant depression

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for treatment-resistant depression (TRD), but its therapeutic mechanisms are unclear. White matter abnormalities are thought to cause network dysfunction underlying TRD. Diffusion tensor imaging (DTI) is an ideal tool for examining neural connections and the integrity of white matter. Few studies have used DTI to investigate the impact of rTMS on alterations of whiter matter in TRD. METHOD 30 young treatment-resistant unipolar depression patients (19 males and 11 females) were enrolled in a double-blind, randomized high-frequency (15 Hz) rTMS treatment study. Seventeen patients were treated with real stimulation, and 13 were treated with sham stimulation. White-matter fractional anisotropy (FA) was evaluated using voxel-based analysis (VBA) of FA maps derived from DTI before and after treatment. Twenty-five age- and gender-matched subjects were examined as a control group. RESULTS In an exploratory VBA method, clusters of fifty voxels or greater that survived a family-wise error (FWE)-corrected threshold of p<0.05 were considered significant. The results revealed significantly reduced FA in the left middle frontal gyrus, with peak coordinates [-18 46 -14] in TRD patients. This reduced FA was significantly improved after active rTMS treatment, but not sham stimulation. FA increases were correlated with decreased depressive symptoms. LIMITATIONS This study requires replication and further clarification in a larger patient population, and optimization of stimulation locations and methods. CONCLUSIONS These results suggest that the efficacy of rTMS on TRD is related to increased white-matter FA in the left middle frontal gyrus.

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

BACKGROUND Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS). METHOD Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study active ((n=19) vs. sham(n=15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls. RESULTS In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS (p<0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed. CONCLUSIONS Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.

Altered regional homogeneity in post-traumatic stress disorder: a restingstate functional magnetic resonance imaging study

ObjectiveLittle is known about the brain systems that contribute to vulnerability to post-traumatic stress disorder (PTSD). Comparison of the resting-state patterns of intrinsic functional synchronization, as measured by functional magnetic resonance imaging (fMRI), between groups with and without PTSD following a traumatic event can help identify the neural mechanisms of the disorder and targets for intervention.MethodsFifty-four PTSD patients and 72 matched traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with blood oxygen level-dependent (BOLD) fMRI and analyzed using the measure of regional homogeneity (ReHo) during the resting state.ResultsPTSD patients presented enhanced ReHo in the left inferior parietal lobule and right superior frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual gyrus, relative to traumatized individuals without PTSD.ConclusionOur findings showed that abnormal brain activity exists under resting conditions in PTSD patients who had been exposed to a major earthquake. Alterations in the local functional connectivity of cortical regions are likely to contribute to the neural mechanisms underlying PTSD.

Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

Background Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures. Methods Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed. Results Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma. Conclusions The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.

White matter integrity alterations in first episode, treatment-naive generalized anxiety disorder

BACKGROUND Several neurobiological models of anxiety disorder posit a primary role for dysfunction of the amygdala and anterior cingulate cortex (ACC). This study tests the hypothesis that patients with generalized anxiety disorder (GAD) have abnormal white matter microstructure in the amygdala and ACC, as inferred from diffusion tensor imaging, compared with healthy controls. METHODS Subjects were 16 right-handed, first-episode, treatment-naive GAD patients without comorbid disorders and 26 matched, healthy comparison controls. All subjects underwent diffusion tensor imaging and structural magnetic resonance imaging brain scanning. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis. Associations between clinical ratings of symptom severity (i.e., the Hamilton Anxiety Scale and the Penn State Worry Questionnaire) and FA were assessed. RESULTS Compared with healthy volunteers, patients demonstrated significantly higher FA in the right amygdala white matter and lower FA in the caudal ACC/mid-cingulate cortex white matter. Higher right amygdala FA correlated significantly with higher Hamilton Anxiety Scale scores and higher Penn State Worry Questionnaire scores. LIMITATIONS The sample size was modest and may contribute to false positive effects. CONCLUSIONS These findings provide the first evidence of an abnormality in white matter microstructure that involves the amygdala and the cingulate cortex in the pathogenesis of GAD, and are consistent with neurobiological models that posit a defect in emotion-related brain regions.

White matter integrity alterations in young healthy adults reporting childhood trauma: A diffusion tensor imaging study:

Objective: To date, insufficient studies have focused on the relationship between childhood trauma and white matter integrity changes in healthy subjects. The aim of the present study was to explore the potential effects of childhood trauma on white matter microstructural changes by using voxel-based diffusion tensor imaging (DTI) to examine alterations in fractional anisotropy (FA) values in a group of young healthy adults. Methods: A total of 21 healthy adults with a history of childhood trauma exposures and 21 age- and sex-matched individuals without childhood trauma were recruited in the present study. The Childhood Trauma Questionnaire was used to assess five aspects of childhood trauma exposures. DTI data were obtained on a Philips 3.0-Tesla scanner. Voxel-based analysis was conducted to compare white matter FA values between groups. Results: Adults with self-reported childhood trauma experiences showed decreased white matter FA values in the genu and body of the corpus callosum and the left occipital fusiform gyrus (p < 0.001 uncorrected, voxel > 100). There was no significant difference in FA values between individuals with single and multiple childhood trauma exposures at the defined threshold. Conclusion: Our findings suggest that childhood trauma is associated with reduced microstructural integrity of the white matter in adulthood. These effects are still evident even in the absence of current psychiatric or medical symptoms, which may represent the vulnerability for developing mental disorders after childhood trauma experiences.

Increased white matter integrity of posterior cingulate gyrus in the evolution of post-traumatic stress disorder

Objective: Functional imaging studies of post-traumatic stress disorder (PTSD) have shown an increased activation of posterior cingulate gyrus (PCG) of the brain. The aim of this study was to explore white matter integrity of PCG in PTSD subjects. Methods: White matter integrity, as determined from fractional anisotropy (FA) value using diffusion tensor imaging, was assessed for PCG in subjects with and without PTSD from a severe mine accident. All subjects were also measured by the PTSD Checklist Civilian Version (PCL-C), the State-Trait Anxiety Inventory (STAI), the logical memory subtest and the visual reproduction subtest of the Wechsler Memory Scale-Revised in China. Sixteen PTSD subjects (8 subjects in each group) in the longitudinal study and 13 PTSD subjects as well as 14 non-PTSD controls in the cross-sectional case–control study were respectively recruited. Results: In the longitudinal study, subjects with PTSD showed increased FA values in left PCG during the follow-up scan. In the cross-sectional study, FA values in bilateral PCG in PTSD subjects were higher than controls. Within the PTSD group (n = 13), FA values in the left PCG correlated positively with logical memory and negatively with PCL-C intrusion and STAI-trait (STAI-t) subscores. FA values in right PCG correlated negatively with STAI-t and STAI-state subscores. Conclusion: These findings suggest that alterations of white matter integrity in PCG link to mnemonic and affective processing in PTSD over the long-term follow-up period.