Linyan Su

Increased Activity Imbalance in Fronto-Subcortical Circuits in Adolescents with Major Depression

Background A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD). Methodology/Principal Findings Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls. Conclusions/Significance The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD.

Combined analyses of gray matter voxel-based morphometry and white matter tract-based spatial statistics in pediatric bipolar mania

BACKGROUND Ample evidence has suggested the presence of gray matter (GM) and white matter (WM) abnormalities in bipolar disorder (BD) patients, including pediatric bipolar disorder (PBD). However, little research has been done in PBD patients that carefully classify the mood states. The aim of the present study is to investigate the brain structural changes in PBD-mania children and adolescents. METHODS Eighteen children and adolescents with bipolar mania (male/female, 6/12) aged 10-18 years old and 18 age- and sex-matched healthy controls were included in the present study. The 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data were obtained on a Siemens 3.0 T scanner. Voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) analysis were conducted to compare the gray matter volume and white matter fractional anisotropy (FA) value between patients and controls. Correlations of the MRI data of each survived area with clinical characteristics in PBD patients were further analyzed. RESULTS As compared with the control group, PBD-mania children showed decreased gray matter volume in the left hippocampus. Meanwhile, significant lower FA value was detected in the right anterior cingulate (AC) in the patient group. No region of increased gray matter volume or FA value was observed in PBD-mania. The hippocampal volume was negatively associated with the Young Mania Rating Scale (YMRS) score when controlling for clinical characteristics in PBD-mania patients, however, there was no significant correlation of FA value of the survived area with illness duration, the onset age, number of episodes, or the YMRS score in PBD-mania patients. LIMITATION The present outcomes require replication in larger samples and verification in medication free subjects. CONCLUSIONS Our findings highlighted that extensive brain structural lesions (including GM and WM) were existed in PBD-mania. The widespread occurrence of structural abnormalities mainly located in the anterior limbic network (ALN) which suggested that this network might contribute to emotional and cognitive dysregulations in PBD.

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.

Altered Regional Homogeneity in Pediatric Bipolar Disorder during Manic State: A Resting-State fMRI Study

Pediatric bipolar disorder (PBD) is a severely debilitating illness, which is characterized by episodes of mania and depression separated by periods of remission. Previous fMRI studies investigating PBD were mainly task-related. However, little is known about the abnormalities in PBD, especially during resting state. Resting state brain activity measured by fMRI might help to explore neurobiological biomarkers of the disorder. Methods: Regional homogeneity (ReHo) was examined with resting-state fMRI (RS-fMRI) on 15 patients with PBD in manic state, with 15 age-and sex-matched healthy youth subjects as controls. Results: Compared with the healthy controls, the patients with PBD showed altered ReHo in the cortical and subcortical structures. The ReHo measurement of the PBD group was negatively correlated with the score of Young Mania Rating Scale (YMRS) in the superior frontal gyrus. Positive correlations between the ReHo measurement and the score of YMRS were found in the hippocampus and the anterior cingulate cortex in the PBD group. Conclusions: Altered regional brain activity is present in patients with PBD during manic state. This study presents new evidence for abnormal ventral-affective and dorsal-cognitive circuits in PBD during resting state and may add fresh insights into the pathophysiological mechanisms underlying PBD.

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.

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.

Altered baseline brain activity in children with bipolar disorder during mania state: a resting-state study

Background Previous functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain’s total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. Methods Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. Results Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD. Conclusion The abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients.

Frequency-Specific Functional Connectivity Density as an Effective Biomarker for Adolescent Generalized Anxiety Disorder

Several neuropsychiatric diseases have been found to influence the frequency-specific spontaneous functional brain organization (SFBO) in resting state, demonstrating that the abnormal brain activities of different frequency bands are associated with various physiological and psychological dysfunctions. However, little is known about the frequency specificities of SFBO in adolescent generalized anxiety disorder (GAD). Here, a novel complete ensemble empirical mode decomposition with adaptive noise method was applied to decompose the time series of each voxel across all participants (31 adolescent patients with GAD and 28 matched healthy controls; HCs) into four frequency-specific bands with distinct intrinsic oscillation. The functional connectivity density (FCD) of different scales (short-range and long-range) was calculated to quantify the SFBO changes related to GAD within each above frequency-specific band and the conventional frequency band (0.01–0.08 Hz). Support vector machine classifier was further used to examine the discriminative ability of the frequency-specific FCD values. The results showed that adolescent GAD patients exhibited abnormal alterations of both short-range and long-range FCD (S-FCD and L-FCD) in widespread brain regions across three frequency-specific bands. Positive correlation between the State Anxiety Inventory (SAI) score and increased L-FCD in the fusiform gyrus in the conventional frequency band was found in adolescents with GAD. Both S-FCD and L-FCD in the insula in the lower frequency band (0.02–0.036 Hz) had the highest classification performance compared to all other brain regions with inter-group difference. Furthermore, a satisfactory classification performance was achieved by combining the discrepant S-FCD and L-FCD values in all frequency bands, with the area under the curve (AUC) value of 0.9414 and the corresponding sensitivity, specificity, and accuracy of 87.15, 92.92, and 89.83%, respectively. This study indicates that the alterations of SFBO in adolescent GAD are frequency dependence and the frequency-specific FCD can potentially serve as a valuable biomarker in discriminating GAD patients from HCs. These findings may provide new insights into the pathophysiological mechanisms of adolescent GAD.

Forgiveness as a moderator of the association between victimization and suicidal ideation

The present study examined the relationships between victimization, suicidal ideation and forgiveness. 962 Chinese middle school students were evaluated using the Chinese versions of the Olweus Bully/Victim Questionnaire (OBVQ), the Positive and Negative Suicide Ideation scale (PANSI) and the Forgiveness Questionnaire (FQ). High victimization and low forgiveness were found to predict increased suicidal ideation. Victimized students with high level of forgiveness reported less suicidal ideation than students with low level of forgiveness. Forgiveness was found to moderate the association between victimization and suicidal ideation and could be a protective factor against suicidal ideation in victimized students.

Lamotrigine-induced facial tic in a pediatric bipolar disorder patient.

Lamotrigine (LTG) is a broad-spectrum antiepilieptic drug used to treat both seizures and bipolar disorder. Recently, there have been several case reports of LTG-induced Tourette’s syndrome in patients. Most of this side effect was reported in patients with partial and generalized seizures, and only three cases were in nonepileptic patients. In contrast, we present the first case, to our knowledge, of a pediatric bipolar patient who developed facial tics during LTG therapy.