Mei Liao

Overlapping and Segregated Resting-State Functional Connectivity in Patients with Major Depressive Disorder With and Without Childhood Neglect

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting‐state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole‐brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph‐theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal‐limbic‐thalamic‐cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole‐brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154–1166, 2014.

Abnormal baseline brain activity in posttraumatic stress disorder: A resting-state functional magnetic resonance imaging study

Little is known about how spontaneous brain activity during the resting state may be altered in posttraumatic stress disorder (PTSD) compared to traumatized individuals. In the current study, we used a measure of amplitude of low-frequency (0.01-0.08 Hz) fluctuation (ALFF) to investigate the regional baseline brain function of this disorder. Fifty-four medication-naive PTSD patients and seventy-two matched traumatized comparison subjects who experienced the Sichuan major earthquake participated in a functional magnetic resonance imaging (fMRI) scan. We analyzed the difference between the PTSD and comparison groups during a resting state using ALFF. PTSD patients showed decreased ALFF values in right lingual gyrus, cuneus, middle occipital gyrus, insula, and cerebellum, and increased ALFF values in right medial and middle frontal gyri, relative to traumatized individuals without PTSD. The ALFF value in the right medial frontal gyrus was positively correlated with severity of the disorder. Our findings show that abnormality of intrinsic brain activity exists under resting conditions in PTSD patients exposed to a major earthquake. Altered ALFF in predominantly right hemisphere cortical and subcortical regions and in cerebellum potentially contribute to the neural mechanisms underlying traumatic memory and symptoms in PTSD.

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.

White matter abnormalities in adolescents with generalized anxiety disorder: a diffusion tensor imaging study

BackgroundPrevious neuroimaging studies have suggested an abnormal neural circuitry of emotion regulation including the amygdala and prefrontal cortex in both adult and adolescent generalized anxiety disorder (GAD) patients. Aberrant integrity of white matter in this neural circuitry has been verified in adult GAD patients. White matter abnormalities in adolescent GAD patients have not been detected.MethodsTwenty-five adolescents with GAD and 24 healthy controls underwent a diffusion tensor imaging scan. Fractional anisotropy (FA) was compared between groups with a voxel-wise Tract-Based Spatial Statistics (TBSS) analysis method.ResultsCompared with healthy controls, adolescents with GAD showed significantly reduced FA in bilateral uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and corona radiata.ConclusionsThe findings in the present study suggest a neural basis of emotion dysregulation in adolescent GAD patients.

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.

Childhood Maltreatment Is Associated with Larger Left Thalamic Gray Matter Volume in Adolescents with Generalized Anxiety Disorder

Background Generalized anxiety disorder (GAD) is a common anxiety disorder that usually begins in adolescence. Childhood maltreatment is highly prevalent and increases the possibility for developing a variety of mental disorders including anxiety disorders. An earlier age at onset of GAD is significantly related to maltreatment in childhood. Exploring the underpinnings of the relationship between childhood maltreatment and adolescent onset GAD would be helpful in identifying the potential risk markers of this condition. Methods Twenty-six adolescents with GAD and 25 healthy controls participated in this study. A childhood trauma questionnaire (CTQ) was introduced to assess childhood maltreatment. All subjects underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry (VBM) was used to investigate gray matter alterations. Results Significantly larger gray matter volumes of the right putamen were observed in GAD patients compared to healthy controls. In addition, a significant diagnosis-by-maltreatment interaction effect for the left thalamic gray matter volume was revealed, as shown by larger volumes of the left thalamic gray matter in GAD patients with childhood maltreatment compared with GAD patients without childhood maltreatment as well as with healthy controls with/without childhood maltreatment. A significant positive association between childhood maltreatment and left thalamic gray matter volume was only seen in GAD patients. Conclusions These findings revealed an increased volume in the subcortical regions in adolescent GAD, and the alterations in the left thalamus might be involved in the association between childhood maltreatment and the occurrence of GAD.

Grey matter volume abnormalities in patients with bipolar I depressive disorder and unipolar depressive disorder: a voxel-based morphometry study

Bipolar disorder and unipolar depressive disorder (UD) may be different in brain structure. In the present study, we performed voxel-based morphometry (VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder (BP1) and 23 patients with UD, and 23 age-, gender-, and education-matched healthy controls (HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups, the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus, while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition, correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together, the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD, and decreased grey matter volume in the right middle cingulate gyrus may be specific to BP1.

Lack of gender effects on gray matter volumes in adolescent generalized anxiety disorder

BACKGROUND Previous epidemiological and clinical studies have reported gender differences in prevalence and clinical features of generalized anxiety disorder (GAD). Such gender differences in clinical phenomenology suggest that the underlying neural circuitry of GAD could also be different in males and females. This study aimed to explore the possible gender effect on gray matter volumes in adolescents with GAD. METHODS Twenty-six adolescent GAD patients and 25 healthy controls participated and underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry (VBM) was used to investigate gray matter alterations. RESULTS Our study revealed a significant diagnosis main effect in the right putamen, with larger gray matter volumes in GAD patients compared to healthy controls, and a significant gender main effect in the left precuneus/posterior cingulate cortex, with larger gray matter volumes in males compared to females. No gender-by-diagnosis interaction effect was found in this study. LIMITATIONS The relatively small sample size in this study might result in a lack of power to demonstrate gender effects on brain structure in GAD. CONCLUSIONS The results suggested that there are differences in gray matter volumes between males and females, but gray matter volumes in GAD are not influenced by gender.