Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.

Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.

Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents.

BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.

Altered spatiotemporal consistency in pediatric bipolar disorder patients with and without psychotic symptoms.

OBJECTIVE: Psychotic symptoms are quite common in patients with pediatric bipolar disorder (PBD) and may affect the symptom severity and prognosis of PBD. However, the potential mechanisms are less well elucidated until now. Thus, the purpose of this study was to investigate the brain functional differences between PBD patients with and without psychotic symptoms. METHOD: A total of 71 individuals including: 27 psychotic PBD (P-PBD), 25 nonpsychotic PBD (NP-PBD), and 19 healthy controls were recruited in the present study. Each subject underwent 3.0 Tesla functional magnetic resonance imaging scan. Four-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was employed to detect the local brain activity changes. Analyses of variance (ANOVA) were used to reveal brain regions with significant differences among three groups groups of individuals, and inter-group comparisons were assessed using post hoc tests. RESULTS: The ANOVA obtained significant among-group FOCA differences in the left triangular inferior frontal gyrus, left supplementary motor area, left precentral gyrus, right postcentral gyrus, right superior occipital gyrus, and right superior frontal gyrus. Compared with the control group, the P-PBD group showed decreased FOCA in the left supplementary motor area and bilateral superior frontal gyrus and showed increased FOCA in the left triangular inferior frontal gyrus. In contrast, the NP-PBD group exhibited decreased FOCA in the right superior occipital gyrus and right postcentral gyrus and showed increased FOCA in the left orbital inferior frontal gyrus. Compared to the NP-PBD group, the P-PBD group showed decreased FOCA in the right superior frontal gyrus. CONCLUSION: The present findings demonstrated that the two groups of PBD patients exhibited segregated brain functional patterns, providing empirical evidence for the biological basis of different clinical outcomes between PBD patients with and without psychotic symptoms.

Altered Functional Integration in the Salience and Default Mode Networks in Euthymic Pediatric Bipolar Disorder.

Accumulating studies demonstrate emotional and cognitive dysregulation in the euthymic period of pediatric bipolar disorder (PBD). However, the relative contribution of functional integration in human brain to disturbed emotion and cognitive function in the euthymic PBD patients remains unclear. In this study, 16 euthymic PBD patients and 16 healthy controls underwent resting-state functional magnetic resonance imaging. A data-driven functional connectivity analysis was used to investigate functional connectivity changes of the euthymic PBD. Compared with healthy controls, the euthymic PBD exhibited greater global functional connectivity density in the left anterior insula and lower global functional connectivity density in the right temporoparietal junction, the left angular gyrus, and the bilateral occipital lobule. A distant functional connectivity analysis demonstrated altered integration within the salience and default mode networks in euthymic PBD. Correlation analysis found that altered functional connectivity of the salience network was related to the reduced performance in the backward digit span test, and altered functional connectivity of the default mode network was related to the Young Mania Rating Scale in euthymic PBD patients. Our findings indicated that disturbed functional integration in salience and default mode networks might shed light on the physiopathology associated with emotional and cognitive dysregulation in PBD.

Associations of serotonin transporter gene promoter polymorphisms and monoamine oxidase A gene polymorphisms with oppositional defiant disorder in a Chinese Han population.

BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder that mainly refers to a recurrent pattern of disobedient, defiant, negativistic and hostile behaviors toward authority figures. Previous studies have showed associations of serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) with behavioral and psychiatric disorders. The purposes of this study were to investigate the potential association of 5-HTT gene promoter polymorphism (5-HTTLPR) and MAOA gene polymorphism with susceptibility to ODD in a Han Chinese school population. METHODS: The 5-HTTLPR gene polymorphism and the MAOA gene polymorphism were genotyped in a case-control study of 257 Han Chinese children (123 ODD and 134 healthy controls). RESULTS: There was significant difference in the allele distribution of 5-HTTLPR (χ2 = 7.849, P = 0.005) between the ODD and control groups. Further, there were significant differences in genotype (χ2 = 5.168, P = 0.023) and allele distributions (χ2 = 10.336, P = 0.001) of the MAOA gene polymorphism that is variable-number tandem repeat (MAOA-uVNTR) between two groups. Moreover, there were significant differences in genotype (χ2 = 4.624, P = 0.032) and allele distributions (χ2 = 9.248, P = 0.002) of MAOA-uVNTR only in the male ODD and healthy groups. CONCLUSIONS: Our results suggest that 5-HTTLPR and MAOA-uVNTR gene variants may contribute to susceptibility to ODD. Further, MAOA-uVNTR gene polymorphism may play a role in susceptibility to ODD only in male children.

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

BACKGROUND: Previous 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. METHODS: Twenty-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. RESULTS: Compared with healthy controls, adolescents with GAD showed significantly reduced FA in bilateral uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and corona radiata. CONCLUSIONS: The findings in the present study suggest a neural basis of emotion dysregulation in adolescent GAD patients.

Alterations of regional homogeneity in pediatric bipolar depression: a resting-state fMRI study.

BACKGROUND: Pediatric bipolar disorder (PBD) has attracted increasing attentions due to its high prevalence and great influence on social functions of children and adolescents. However, the pathophysiology underlying PBD remains unclear. In the present study, the resting-state functional magnetic resonance imaging (fMRI) was used to detect abnormalities of baseline brain functions in depressed PBD youth. METHODS: Seventeen youth with PBD-depression aged 10 - 18 years old and 18 age- and sex-matched normal controls were recruited in this study. The fMRI data under resting state were obtained on a Siemens 3.0 Tesla scanner and were analyzed using the regional homogeneity (ReHo) method. Correlations between the ReHo values of each survived area and the severity of depression symptoms in patients were further analyzed. RESULTS: As compared with the control group, PBD-depression patients showed decreased ReHo in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and the right putamen. Significant negative correlations of the mood and feelings questionnaire scores with mean ReHo values in the medial frontal gyrus and the right middle frontal gyrus in PBD-depression patients were observed. CONCLUSION: Our results suggest that extensive regions with altered baseline brain activities are existed in PBD-depression and these brain regions mainly locate in the fronto-limbic circuit and associated striatal structures. Moreover, the present findings also add to our understanding that there could be unique neuropathophysiological mechanisms underlying PBD-depression.

A Multifunctional Additive Based on the Cation-Anion Synergistic Effect for Highly Stable Zinc Metal Anodes.

The Zn dendrite and hydrogen evolution reaction have been a "stubborn illness" for the life span of zinc anodes, which significantly hinders the development of aqueous zinc batteries (AZBs). Herein, considering the ingenious molecular structure, a multifunctional additive based on the synergistic regulation of cations and anions at the interface is designed to promote a dendrite-free and stable Zn anode. Theoretical calculations and characterization results verified that the electrostatic shield effect of the cation, the solvation sheath structure, and the bilayer structural solid electrolyte film (SEI) jointly account for the uniform Zn deposition and side reaction suppression. Ultimately, a remarkably high average Coulombic efficiency (CE) of 99.4% is achieved in the Zn||Cu cell for 300 cycles, and a steady charge/discharge cycling over 3000 and 300 h at 1.0 mA cm-2/1.0 mAh cm-2 and 10 mA cm-2/10 mAh cm-2 is obtained in the Zn||Zn cell. Furthermore, the assembled full battery demonstrates a prolonged cycle life of 2000 cycles.

Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder.

BACKGROUND: Impaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. METHODS: Thirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. RESULTS: Compared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SIGNIFICANCE: The study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. CONCLUSIONS: Distinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

[Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents].

OBJECTIVE: To investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs). METHODS: A total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD. RESULTS: The distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents. CONCLUSIONS: It is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.

The Different Impact of Depressive or Manic First-episode on Pediatric Bipolar Disorder Patients: Evidence From Resting-state fMRI.

Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis of bipolar disorder. However, the physiological and pathological differences of pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The purpose of this study was to investigate the differences of clinical, cognitive function and intrinsic brain networks in PBD patients with first-episode depression and first-episode mania. A total of 63 participants, including 43 patients and 20 healthy controls, underwent resting-state fMRI scans. PBD patients were classified as first-episode depressive and first-episode manic based on their first-episode symptoms. Cognitive tests were used to measure attention and memory of all participants. Independent component analysis (ICA) was used to extract the salience network (SN), default-mode network (DMN), central executive network (ECN) and limbic network (LN) for each participant. Spearman rank correlation analysis was performed between abnormal activation and clinical and cognitive measures. The results showed that there were differences in cognitive functions such as attention and visual memory between first-episode depression and mania, as well as differences activation in anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), precuneus, inferior parietal cortex and parahippocampus. And significant associations of brain activity with clinical assessments or cognition were found in different patients. In conclusion, we found differential impairments in cognitive and brain network activation in first-episode depressive and first-episode manic PBD patients, and correlations were found between these impairments. These evidences may shed light on the different developmental paths of bipolar disorder.

The disruption of functional connectome gradient revealing networks imbalance in pediatric bipolar disorder.

OBJECTIVE: Pediatric bipolar disorder (PBD) is a psychiatric disorder marked by alteration of brain networks. However, the understanding of these alterations in topological organization still unclear. This study aims to leverage the functional connectome gradient to examine changes in functional network hierarchy in PBD. METHOD: Connectome gradients were used to scrutinize the differences between functional gradient map in PBD patients (n = 68, aged 11 to 18) and healthy controls (HC, n = 37, aged 11 to 18). The association between regional altered gradient scores and clinical factors was examined. We further used Neurosynth to determine the correlation of the cognitive terms with the PBD principal gradient changes. RESULTS: Global topographic alterations were exhibited in the connectome gradient in PBD patients, involving gradient variance, explanation ratio, gradient range, and gradient dispersion in the principal gradient. Regionally, PBD patients revealed that the default mode network (DMN) held the most majority of the brain areas with higher gradient scores, whereas a higher proportion of brain regions with lower gradient scores in the sensorimotor network (SMN). These regional gradient differences exhibited significant correlation with clinical features and meta-analysis terms including cognitive behavior and sensory processing. CONCLUSION: Functional connectome gradient presents a thorough investigation of large-scale networks hierarchy in PBD patients. This exhibited excessive segregation between DMN and SMN supports the theory of imbalance in top-down control and bottom-up in PBD and provides a possible biomarker for diagnostic assessment.

Gene expression changes in peripheral blood from Chinese Han patients with Tourette syndrome.

To evaluate whether gene expression in chromosome 15q13-q22.3 region is responsible for the development of Tourette syndrome (TS). Eighty-four unrelated Chinese Han patients with TS (male/female = 68/16; mean age 9.92 ± 3.98 years) and 100 sex, age, and ethnicity matched normal controls (male/female = 80/20; mean age 10.90 ± 5.86 years) were enrolled in this study. We performed quantitative real-time PCR on a subset of seven genes: the L-histidine decarboxylase gene (HDC), the HECT domain and RCC-1 like domain 1 gene (HERC1), the HECT domain and RCC-1 like domain 2 gene (HERC2), the cholinergic receptor, neuronal nicotinic alpha polypeptide 7 gene (CHRNA7), the ubiquitin protein ligase E3A gene (UBE3A), the ubiquitin specific peptidase 3 gene (USP3) and the amyloid precursor protein-binding protein A2 gene (APBA2) previously reported to be stably expressed in brain tissue. A significant difference was shown for the APBA2 gene expression of peripheral lymphocytes between Chinese Han TS group and healthy controls (relative expression: 0.21 ± 0.16-fold decrease in patients versus normal, P < 0.01). Indicating that the APBA2 gene is a promising peripheral blood biomarker that discriminates between patients with TS and healthy subjects. Further studies into this gene and its protein products may provide insights into the pathogenesis of TS.

Mutation screening of the HDC gene in Chinese Han patients with Tourette syndrome.

Tourette Syndrome (TS) is a complex neuropsychiatric disorder characterized by vocal and motor tics. While environmental causes have been proposed to play a role, genetic factors are believed to be the main determinants of the disorder and its clinical manifestations. Recently, a heterozygous W317X mutation in the histidine decarboxylase gene (HDC) was reported to be responsible for TS in a two-generation pedigree. To investigate whether the HDC gene play a role in TS in Chinese Han population, we performed genetic analysis of the coding region of the HDC gene in 100 Chinese Han patients with TS. Three variants were found including a C > T transition (IVS1 + 52C > T), a novel C > A transition (c.426C > A) in exon 4, and a novel G > A transition (c.1743G > A) in exon 12, both predicted with no amino acid change. Extended analysis was conducted in a total of 120 TS patients and 240 sex, age, and ethnicity matched healthy controls. No significant differences in genotypic and allele distribution between patients and controls for these three variants (P = 0.274, P = 1.000 and P = 0.632 for genotypic distribution, respectively; P = 0.143, P = 1.000 and P = 0.582 for allele distribution, respectively) were observed, suggesting variants in the HDC gene may play little or no role in TS susceptibility in Chinese Han population.

Pallidal volume reduction and prefrontal-striatal-thalamic functional connectivity disruption in pediatric bipolar disorders.

BACKGROUND: As a crucial node of the corticolimbic model, the striatum has been demonstrated in modulating emotional cues in pediatric bipolar disorders (PBD), the striatal distinction in structure and function between PBD-I and PBD-II remains unclear. METHODS: MRI data of 36 patients in PBD-I, 22 patients in PBD-II and 19 age-gender matched healthy controls (HCs) were processed. Here, we investigated structural and functional alterations of 8 subregions of striatum (bilateral nucleus accumbens, caudate, putamen and globus pallidus) by analyzing MRI data. RESULTS: We found volume reduction of the right pallidum, the significant positive correlation between the number of episodes and the functional connectivity between left pallidum and right caudate in PBD-I patients, abrupted prefrontal-striatal-thalamic functional connectivity in PBD-I group and decreased functional connectivity in PBD-II relative to HCs and PBD-I. LIMITATIONS: Future studies should enroll more subjects and adopt a longitudinal perspective, which could help to discover striatum structural or functional alterations during subject-specific clinical progress in different states. CONCLUSIONS: Results of the present study confirmed that structural and functional abnormality of striatum may be helpful in identifying PBD clinical types as distinctive biomarkers. The interruptions of the prefrontal-striatal-thalamic circuits may provide advantageous evidence for expounding the role of striatum in bipolar disorders etiology. Thus, potential mechanisms of dysfunction striatum need to be formulated and reconceptualized with multimodal neuroimaging studies in future.

Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder.

Background: Pediatric bipolar disorder (PBD) has been proven to be related to abnormal brain structural connectivity, but how the abnormalities in PBD correlate with gene expression is debated. Objective: This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD. Methods: Morphometric similarity networks (MSN) were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants (59 patients and 43 controls). Partial least squares (PLS) regression was used to calculate MSN differences related to transcriptomic data in AHBA. The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools. Results: MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants. MSN differences were spatially correlated with the PBD-related weighted genes. The weighted genes were enriched for "trans-synaptic signaling" and "regulation of ion transport", and showed significant specific expression in excitatory and inhibitory neurons. Conclusions: This study identified the genes that contributed to structural network aberrations in PBD. It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.

Machine learning algorithm performance evaluation in structural magnetic resonance imaging-based classification of pediatric bipolar disorders type I patients.

The diagnosis based on clinical assessment of pediatric bipolar disorder (PBD) may sometimes lead to misdiagnosis in clinical practice. For the past several years, machine learning (ML) methods were introduced for the classification of bipolar disorder (BD), which were helpful in the diagnosis of BD. In this study, brain cortical thickness and subcortical volume of 33 PBD-I patients and 19 age-sex matched healthy controls (HCs) were extracted from the magnetic resonance imaging (MRI) data and set as features for classification. The dimensionality reduced feature subset, which was filtered by Lasso or f_classif, was sent to the six classifiers (logistic regression (LR), support vector machine (SVM), random forest classifier, naïve Bayes, k-nearest neighbor, and AdaBoost algorithm), and the classifiers were trained and tested. Among all the classifiers, the top two classifiers with the highest accuracy were LR (84.19%) and SVM (82.80%). Feature selection was performed in the six algorithms to obtain the most important variables including the right middle temporal gyrus and bilateral pallidum, which is consistent with structural and functional anomalous changes in these brain regions in PBD patients. These findings take the computer-aided diagnosis of BD a step forward.

Manic and euthymic states in pediatric bipolar disorder patients during an emotional Go/Nogo task: A functional magnetic resonance imaging study.

BACKGROUND: Neural abnormalities in emotional response inhibition still exist in the euthymic phase of bipolar disorder (BD). Few studies on comparisons of functional magnetic resonance imaging (fMRI) manifestations between different mood phases of pediatric bipolar disorder (PBD) have ever been published. The goal of this study was to explore the differences in neural activities between manic and euthymic PBD during emotional response inhibition. METHODS: Simultaneous imaging of neural activity was recorded during an emotional Go/Nogo paradigm and the effect of emotional response inhibition was analyzed. Neural activities were compared between the three groups. RESULTS: In the presence of emotional versus neutral distractors, both manic and euthymic PBD subjects similarly showed widespreadly increased activities in the cognitive and emotional regulation circuits compared with healthy individuals. Compared with euthymic PBD patients, those with manic PBD exhibited increased activities in the left superior frontal gyrus. Hyperactivity in the left superior frontal, left middle frontal and right inferior frontal gyrus in manic PBD was positively associated with false response errors. CONCLUSION: Increased activity in the left superior frontal gyrus may be characteristic of manic episodes in PBD patients, and such a disparity between manic and euthymic phrases may attribute to more severe emotional dysregulation.

Brain structural alterations in pediatric bipolar disorder patients with and without psychotic symptoms.

BACKGROUND: Bipolar disorder (BD) with psychotic symptoms is a specific phenotype that presents greater risk of relapse and worse outcomes than nonpsychotic BD, however, the underlying mechanisms remain unknown and are less revealed in youth. Thus, the aims of the present study were to investigate brain structural alterations in pediatric bipolar disorder (PBD) patients with and without psychotic symptoms, and specifically to evaluate the impact of psychotic features on gray matter volume (GMV) in PBD patients. METHOD: A total of 73 individuals were recruited into three groups, n = 28, psychotic PBD, P-PBD; n = 26, nonpsychotic PBD, NP-PBD; and n = 19, healthy controls, HC. All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GMV alterations. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. RESULTS: The ANOVA revealed significant GMV differences among three groups in the bilateral amygdala-hippocampus-parahippocampal complex (AMY-HIS-ParaHIS complex), left superior temporal gyrus (STG), left inferior frontal gyrus (IFG), bilateral putamen (PUT), left precentral gyrus (PG), left supramarginal gyrus (SMG), and right inferior parietal lobule (IPL). Compared with HCs, P-PBD patients showed decreased GMV in the bilateral AMY-HIS-ParaHIS complex, left STG, left IFG, bilateral PUT, and left PG; while NP-PBD patients exhibited decreased GMV in the left IFG, left PG, left SMG, and right IPL. Furthermore, P-PBD patients showed increased GMV in the right IPL when comparing to NP-PBD patients. LIMITATION: The present findings require replication in larger samples and verification in medication free subjects. CONCLUSION: The present findings suggested that psychotic features in PBD were associated with extensive brain structural lesions mainly located in the prefrontal-limbic-striatum circuit, which might represent the pathological basis of more sever symptoms in patients with psychotic PBD.