PICOTEES: a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts.

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://birthdefectlab.cn:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established. METHODS: We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors. RESULTS: We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811-0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity. CONCLUSIONS: These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

Multivariate associations between behavioural dimensions and white matter across children and adolescents with and without attention-deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder. Integrity of white matter microstructure plays a key role in the neural mechanism of ADHD presentations. However, the relationships between specific behavioural dimensions and white matter microstructure are less well known. This study aimed to identify associations between white matter and a broad set of clinical features across children and adolescent with and without ADHD using a data-driven multivariate approach. METHOD: We recruited a total of 130 children (62 controls and 68 ADHD) and employed regularized generalized canonical correlation analysis to characterize the associations between white matter and a comprehensive set of clinical measures covering three domains, including symptom, cognition and behaviour. We further applied linear discriminant analysis to integrate these associations to explore potential developmental effects. RESULTS: We delineated two brain-behaviour dimensional associations in each domain resulting a total of six multivariate patterns of white matter microstructural alterations linked to hyperactivity-impulsivity and mild affected; executive functions and working memory; externalizing behaviour and social withdrawal, respectively. Apart from executive function and externalizing behaviour sharing similar white matter patterns, all other dimensions linked to a specific pattern of white matter microstructural alterations. The multivariate dimensional association scores showed an overall increase and normalization with age in ADHD group while remained stable in controls. CONCLUSIONS: We found multivariate neurobehavioral associations exist across ADHD and controls, which suggested that multiple white matter patterns underlie ADHD heterogeneity and provided neural bases for more precise diagnosis and individualized treatment.

scFed: federated learning for cell type classification with scRNA-seq.

The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and complexity in biological tissues. However, the nature of large, sparse scRNA-seq datasets and privacy regulations present challenges for efficient cell identification. Federated learning provides a solution, allowing efficient and private data use. Here, we introduce scFed, a unified federated learning framework that allows for benchmarking of four classification algorithms without violating data privacy, including single-cell-specific and general-purpose classifiers. We evaluated scFed using eight publicly available scRNA-seq datasets with diverse sizes, species and technologies, assessing its performance via intra-dataset and inter-dataset experimental setups. We find that scFed performs well on a variety of datasets with competitive accuracy to centralized models. Though Transformer-based model excels in centralized training, its performance slightly lags behind single-cell-specific model within the scFed framework, coupled with a notable time complexity concern. Our study not only helps select suitable cell identification methods but also highlights federated learning's potential for privacy-preserving, collaborative biomedical research.

Prevalence of mental disorders in school children and adolescents in China: diagnostic data from detailed clinical assessments of 17,524 individuals.

BACKGROUND: To date, no national-scale psychiatric epidemiological survey for children and adolescents has been conducted in China. In order to inform government officials and policymakers and to develop a comprehensive plan for service providers, there was a clear need to conduct an up-to-date systematic nationwide psychiatric epidemiological survey. METHODS: We conducted a two-stage large-scale psychiatric point prevalence survey. Multistage cluster stratified random sampling was used as the sampling strategy. Five provinces were selected by comprehensively considering geographical partition, economic development, and rural/urban factors. In Stage 1, the Child Behavior Checklist was used as the screening tool. In Stage 2, Mini-International Neuropsychiatric Interview for Children and Adolescents and a diagnostic process based on the Diagnostic and Statistical Manual were used to make the diagnoses. Sampling weights and poststratification weights were employed to match the population distributions. Exploratory analyses were also performed using socio-demographic factors. Prevalence in socio-demographic factor subgroups and overall were estimated. Rao-Scott adjusted chi-square tests were utilized to determine if between-group differences were present. Factor interactions were checked by logistic regression analyses. RESULTS: A total of 73,992 participants aged 6-16 years of age were selected in Stage 1. In Stage 2, 17,524 individuals were screened and diagnosed. The weighted prevalence of any disorder was 17.5% (95% CI: 17.2-18.0). Statistically significant differences in prevalence of any psychiatric disorder were observed between sexes [χ2 (1, N = 71,929) = 223.0, p < .001], age groups [χ2 (1, N = 71,929) = 18.6, p < .001] and developed vs. developing areas [χ2 (1, N = 71,929) = 2,129.6, p < .001], while no difference was found between rural and urban areas [χ2 (1, N = 71,929) = 1.4, p = .239]. Male, younger individuals, children, and adolescents from developed areas had higher prevalence of any psychiatric disorder. The prevalence of any psychiatric disorder was found to decrease with the age in the male group, while the female group increased with the age. Individuals diagnosed with attention-deficit hyperactivity disorder, oppositional defiant disorder, a tic disorder, conduct disorder, and major depression disorder had the highest rates of comorbidity. CONCLUSIONS: The prevalence of any psychiatric disorder we found is the highest ever reported in China. These results urgently need to be addressed by public mental health service providers and policymakers in order to provide access to the necessary treatments and to reduce the long-term negative impact of these conditions on families and the society as a whole.

Altered single-subject gray matter structural networks in drug-naïve attention deficit hyperactivity disorder children.

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug-naïve children with ADHD and 83 age-matched healthy controls. Single-subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug-naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.

Investigation of white matter functional networks underlying different behavioral profiles in attention-deficit/hyperactivity disorder.

Background: Cortical functional network alterations have been widely accepted as the neural basis of attention-deficit/hyperactivity disorder (ADHD). Recently, white matter has also been recognized as a novel neuroimaging marker of psychopathology and has been used as a complement to cortical functional networks to investigate brain-behavior relationships. However, disorder-specific features of white matter functional networks (WMFNs) are less well understood than those of gray matter functional networks. In the current study, we constructed WMFNs using a new strategy to characterize behavior-related network features in ADHD. Methods: We recruited 46 drug-naïve boys with ADHD and 46 typically developing (TD) boys, and used clustering analysis on resting-state functional magnetic resonance imaging data to generate WMFNs in each group. Intrinsic activity within each network was extracted, and the associations between network activity and behavior measures were assessed using correlation analysis. Results: Nine WMFNs were identified for both ADHD and TD participants. However, boys with ADHD showed a splitting of the inferior corticospinal-cerebellar network and lacked a cognitive control network. In addition, boys with ADHD showed increased activity in the dorsal attention network and somatomotor network, which correlated positively with attention problems and hyperactivity symptom scores, respectively, while they presented decreased activity in the frontoparietal network and frontostriatal network in association with poorer performance in response inhibition, working memory, and verbal fluency. Conclusions: We discovered a dual pattern of white matter network activity in drug-naïve ADHD boys, with hyperactive symptom-related networks and hypoactive cognitive networks. These findings characterize two distinct types of WMFN in ADHD psychopathology.

The prevalence of behavioral and emotional problems among Chinese school children and adolescents aged 6-16: a national survey.

Improving the mental health of children and adolescents is a critical priority in China. However, only minimal information is available concerning the prevalence of mental disorders. In the present study, a two-stage national survey has been completed in five regions of China. In the first stage, data from the Achenbach Child Behavior Checklist (CBCL) were collected for each participant to identify the prevalence of the behavioral and emotional problems in China. A multistage cluster stratified random sampling design was used, and a total of 71,929 individuals aged 6-16 years were collected. In this large cohort, 36,893 (49.86%) were males, and 49,015 (66.24%) were living in urban communities. Overall, 17.6% (90% confidence interval 17.4%, 17.9%) of the children and adolescents were identified as having behavioral and emotional problems. Moreover, age and sex effect was found for the CBCL scores. The boys' cohort had a higher prevalence of behavioral and emotional problems than girls (18.6% versus 16.6%). In the older cohort aged 12-16, the prevalence was higher than for the younger cohort aged 6-11 (19.0% versus 15.9%). Notably, it seems that the prevalence of the behavioral and emotional problems for children and adolescents had a rise in the past 30 years, but the scarcity of pediatric psychiatrists in China needs to be addressed. To reduce the behavioral and emotional problems, the whole society, including mental health providers, educators, and parents, needs to focus on and pay more attention to it. It will have long-term benefits for China.

Disrupted brain functional networks in drug-naïve children with attention deficit hyperactivity disorder assessed using graph theory analysis.

Neuroimaging studies have revealed functional brain network abnormalities in attention deficit hyperactivity disorder (ADHD), but the results have been inconsistent, potentially related to confounding medication effects. Furthermore, specific topological alterations in functional networks and their role in behavioral inhibition dysfunction remain to be established. Resting-state functional magnetic resonance imaging was performed on 51 drug-naïve children with ADHD and 55 age-matched healthy controls. Brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and graph theory was used to analyze network topological properties. The Stroop test was used to assess cognitive inhibitory abilities. Nonparametric permutation tests were used to compare the topological architectures in the two groups. Compared with healthy subjects, brain networks in ADHD patients demonstrated altered topological characteristics, including lower global (FDR q = 0.01) and local efficiency (p = 0.032, uncorrected) and a longer path length (FDR q = 0.01). Lower nodal efficiencies were found in the left inferior frontal gyrus and anterior cingulate cortex in the ADHD group (FDR both q < 0.05). Altered global and nodal topological efficiencies were associated with the severity of inhibitory cognitive control deficits and hyperactivity symptoms in ADHD (p <0 .05). Alterations in network topologies in drug-naïve ADHD patients indicate weaker small-worldization with decreased segregation and integration of functional brain networks. Deficits in the cingulo-fronto-parietal attention network were associated with inhibitory control deficits.

Characterization of cortical and subcortical abnormalities in drug-naive boys with attention-deficit/hyperactivity disorder.

BACKGROUND: The current study was designed to investigate the anatomical differences in cortical and subcortical morphometry between drug-naive boys with attention-deficit/hyperactivity disorder (ADHD) and healthy controls (HCs) using three-dimensional T1-weighted imaging and to explore the effects of age on morphometric abnormalities. METHODS: Fifty-three drug-naive boys with ADHD and 53 HCs underwent high-resolution anatomical magnetic resonance (MR) imaging using a 3-T MR scanner. The FreeSurfer image analysis suite was used to obtain measures of cortical volume, thickness, and surface area, as well as the volumes of 14 subcortical structures. Statistically significant differences in measures between children with ADHD and HCs were evaluated using a least general linear model, with the intracranial volume and age as covariates. RESULTS: Compared to HCs, boys with ADHD exhibited an increased cortical volume in the left frontal eye field (FEF), a decreased surface area in the left ventral frontal cortex (VFC), and a decreased volume in the right putamen (cluster-wise p < 0.05; Monte Carlo-corrected). Moreover, we also observed age-related differences in FEF and VFC between groups. LIMITATIONS: The cross-sectional study design limited inferences about the effects of age on regions displaying morphometric differences. CONCLUSIONS: To our knowledge, this study is the first to characterize the cortical morphometry, including volume, thickness and surface area, of drug-naive boys with ADHD at the whole brain level; which provided detailed information about neuroanatomical alterations in attention systems beyond effects reported in previous studies at the lobe and sub-lobe levels. Based on our results, boys with ADHD presented significant alterations in cortical and subcortical morphology in several important nodes of the attention network.

Activation of Dorsomedial Hypothalamic Neurons Promotes Physical Activity and Decreases Food Intake and Body Weight in Zucker Fatty Rats.

Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker (Lepr(fa), ZF) and Koletsky (Lepr(fak), SHROB) rats. Ad lib-fed SHROB rats with locked running wheels became hyperphagic and gained body weight rapidly. These alterations were not ameliorated in ad lib-fed SHROB rats with voluntary access to running wheels, but the body weight of SHROB rats with running wheel access was significantly decreased when they were pair-fed to the amounts consumed by lean controls. Determinations of hypothalamic gene expression revealed that sedentary ad lib-fed SHROB rats had increased expression of neuropeptide Y (Npy) and decreased expression of pro-opiomelanocortin (Pomc) in the arcuate nucleus (ARC). Both ARC Npy and Pomc expression were further altered under running and pair-fed conditions, indicating that both genes are appropriately regulated in response to increased energy demands or alterations caused by running activity and food restriction. Strikingly, c-Fos immunohistochemistry revealed that while voluntary running activity elevated the number of c-Fos positive cells in the DMH (particularly in the ventral and caudal subregions) of intact rats, such activation was not observed in ZF rats. Using adeno-associated virus (AAV)-mediated expression of the designer receptors hM3D(Gq) in the ventral and caudal DMH of ZF rats, we found that chemogenetic stimulation of neurons in these DMH subregions via injection of the designer drug clozapine N-oxide (CNO) significantly increased their running activity and reduced their food intake and body weight. Together, these results demonstrate that activation of ventral and caudal DMH neurons promotes physical activity and decreases food intake and body weight and suggest that intact DMH neural signaling is likely crucial for exercise-induced reductions of food intake and body weight in obese rats lacking leptin receptors.

Clinical characterization of autoimmune encephalitis and psychosis.

BACKGROUND AND PURPOSE: Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy. METHODS: Data for patients admitted to the West China Hospital with autoimmune encephalitis diagnoses from 2015 to 2016 were collected and the corresponding clinical features were analyzed. RESULTS: We ultimately included 70 patients with autoimmune encephalitis: 56 (80%) anti-NMDAR encephalitis patients, 8 (11%) LGI1 antibody encephalitis patients, and 6 (9%) GABAbR antibody encephalitis patients. The median age of the 70 patients was 33years, 40% were female, and the initial symptoms in 31 patients (44%) were psychiatric in nature. Psychiatric disturbance appeared in 58 patients (83%) during inpatient treatment, after which 57 patients (81%) recovered. CONCLUSIONS: Many patients with autoimmune encephalitis present psychotic symptoms; psychiatric symptoms typically appear before neurological features emerge. Timely diagnosis and treatment may yield favorable prognosis.

[Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder(ADHD)].

Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neuro-developmental disorders occurring in childhood,characterized by symptoms of age-inappropriate inattention,hyperactivity/impulsivity,and the prevalence is higher in boys.Although gray matter volume deficits have been frequently reported for ADHD children via structural magnetic resonance imaging,few of them had specifically focused on male patients.The present study aimed to explore the alterations of gray matter volumes in medicated-naive boys with ADHD via a relatively new voxel-based morphometry technique.According to the criteria of DSM-IV-TR,43medicated-naive ADHD boys and 44age-matched healthy boys were recruited.The magnetic resonance image(MRI)scan was performed via a 3T MRI system with three-dimensional(3D)spoiled gradient recalled echo(SPGR)sequence.Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated lie algebra in SPM8 was used to preprocess the3DT1-weighted images.To identify gray matter volume differences between the ADHD and the controls,voxelbased analysis of whole brain gray matter volumes between two groups were done via two sample t-test in SPM8 with age as covariate,threshold at P<0.001.Finally,compared to the controls,significantly reduced gray matter volumes were identified in the right orbitofrontal cortex(peak coordinates[-2,52,-25],t=4.01),and bilateral hippocampus(Left:peak coordinates[14,0,-18],t=3.61;Right:peak coordinates[-14,15,-28],t=3.64)of ADHD boys.Our results demonstrated obvious reduction of whole brain gray matter volumes in right orbitofrontal cortex and bilateral hippocampus in boys with ADHD.This suggests that the abnormalities of prefrontal-hippocampus circuit may be the underlying cause of the cognitive dysfunction and abnormal behavioral inhibition in medicatednaive boys with ADHD.

Neuroanatomical deficits correlate with executive dysfunction in boys with attention deficit hyperactivity disorder.

Previous structural imaging studies have revealed gray matter volume abnormalities to reflect the etiology of attention deficit hyperactivity disorder (ADHD), however, which are confounded by age, medication and comorbidity and also ignore the core feature of brain structure in the executive impairments of ADHD. In the present study, we explored gray matter volume abnormalities in male children and adolescents with ADHD who were drug-naive and without comorbidities, and tried to connect structural data and behavioral executive dysfunction to provide more information regarding the brain-behavior relationships in ADHD. Seventy-two male subjects (37 patients and 35 controls) underwent three-dimensional high-resolution structural magnetic resonance imaging and executive function assessments, including the Stroop Color-Word Test and Wisconsin Card Sorting Test (WCST). Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated Lie algebra was used to identify gray matter volume differences between the ADHD and controls. Correlation analyses were performed to identify neuroanatomical deficits that were associated with executive dysfunctions. Significantly reduced gray matter volumes were identified in the right orbitofrontal cortex, right primary motor/premotor cortex, left anterior cingulate cortex and left posterior midcingulate cortex of ADHD patients compared with controls (P<0.05, corrected for family-wise errors). In patients group, the gray matter volumes of the right orbitofrontal cortex and left posterior midcingulate cortex were positively correlated with the completed categories on the WCST, and the gray matter volume of the left posterior midcingulate cortex was negatively correlated with the total and non-perseverative errors on the WCST (P<0.05). The present findings show gray matter volume reductions in motor regions as well as the orbitofrontal and cingulate cortex; this evidence supports theories that suggest frontal abnormalities in children and adolescents with ADHD at early illness stage. The correlations between structural abnormalities and executive dysfunction suggest that neuroanatomical substrate deficits are implicated in the pathophysiology of ADHD.

Prevalence of mental disorders in 6-16-year-old students in Sichuan province, China.

To investigate the point prevalence of mental disorders in school students, multistage cluster stratified random sampling and two-phase survey methods were used to identify 40 primary and middle schools. The students were screened using the Chinese version of the Child Behavior Checklist and diagnosed using the Mini International Neuropsychiatric Interview. The prevalence of behavioral problems was 19.13%. The prevalence of behavioral problems significantly differed by sex, age, city of residence, and caretaker. The six-month prevalence of any mental disorder was 15.24% (95% CI: 15.49%-16.97%). Psychiatric disorders were more prevalent in boys (17.33%) relative to girls (13.11%; p < 0.01). The prevalence of mental disorders significantly differed by community and caretaker, and 36.46% of students exhibited comorbidity. Results demonstrated important mental health issues, with a high incidence of comorbidities, in this population. Students' mental health requires increased attention, particularly in poverty-stricken areas and left-behind children and adolescents.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. METHODS: We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners' Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. RESULTS: Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. LIMITATIONS: This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. CONCLUSION: Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.

Association of Catechol-O-methyltransferase val/met polymorphism with cognitive function in Gilles de la Tourette syndrome patients.

Gilles de la Tourette syndrome (GTS) is a kind of neuropsychiatric disorder with childhood onset. The cognitive dysfunction caused by GTS could affect the growth and learning of children and adolescents. The mechanism of cognitive functions was associated with dopaminergic system, thus we access the associations between polymorphism of some dopaminergic system-related genes including Catechol-O-methyltransferase (COMT) met/val, Dopamine receptor D4 (DRD4) exon III 48 bp VNTR (variable number of tandem repeats), Interleukin 1 (IL-1) Ra 86 bp and IL-1ß exon 5, and cognitive functions in GTS patients. Genotyping analysis was performed through polymerase chain reaction (PCR). Test for cognitive functions of GTS patients included modified wisconsin card sorting test (WCST), trail making test, visual reproduction test, stroop test and verbal fluency test. The patients with COMT met/met genotype showed less perseverative errors in modified WCST test compared with patients with COMT val/val genotype (P < 0.05). Meanwhile, patients without allele val had better delayed memory in visual reproduction test, less errors in the stroop test and less perseverative errors in modified WCST test compared with patients with allele val (P < 0.05). However, no significant difference was found in cognitive functions among patients with different genotypes or alleles of polymorphisms of DRD4 exon III 48 bp VNTR, IL-1 Ra 86 bp and IL-1ß exon 5 (P > 0.05). Polymorphism of COMT met/val was correlated with cognitive functions in GTS patients. This study provided basis for the analysis of molecular genetic pathology of cognitive dysfunctions in GTS.

Intrinsic brain abnormalities in attention deficit hyperactivity disorder: a resting-state functional MR imaging study.

PURPOSE: To explore alterations of regional and network-level neural function using resting-state functional magnetic resonance (MR) imaging in children and adolescents with attention deficit hyperactivity disorder (ADHD) and to assess the association between these alterations of intrinsic neural activity and executive dysfunction in ADHD. MATERIALS AND METHODS: This prospective study was approved by the local ethical committee, and written informed consent was obtained from guardians of all participants. Thirty-three boys with ADHD who were not receiving medication and who were without comorbidity (aged 6-16 years) and 32 healthy control subjects (aged 8-16 years) underwent imaging by using resting-state functional MR imaging. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were calculated to examine regional neural function and functional integration, respectively, and were compared between patients and control subjects by using the voxel-based two-sample t test, while Pearson correlation analyses were performed to identify neural correlates of executive function measured with the Wisconsin Card Sorting Test and the Stroop Color-Word Test. RESULTS: Relative to healthy control subjects, patients with ADHD showed impaired executive function (P < .05), along with the following: lower ALFF in the left orbitofrontal cortex (P = .004) and the left ventral superior frontal gyrus (P = .003); higher ALFF in the left globus pallidus (P = .004), the right globus pallidus (P = .002), and the right dorsal superior frontal gyrus (P = .025); lower long-range FC in the frontoparietal and frontocerebellar networks; and higher FC in the frontostriatal circuit that correlated across subjects with ADHD with the degree of executive dysfunction (P < .05). CONCLUSION: These findings of focal spontaneous hyper- and hypofunction, together with altered brain connectivity in the large-scale resting-state networks, which correlates with executive dysfunction, point to a connectivity-based pathophysiologic process in ADHD.

Neural hyperactivity related to working memory in drug-naive boys with attention deficit hyperactivity disorder.

BACKGROUND: Impaired working memory is thought to be a core feature of attention deficit hyperactivity disorder (ADHD). Previous imaging studies investigating working memory in ADHD have used tasks involving different cognitive resources and ignoring the categorical judgments about objects that are essential parts of performance in visual working memory tasks, thus complicating the interpretation of their findings. In the present study, we explored differential neural activation in children and adolescents with ADHD and in healthy controls using functional magnetic resonance imaging (fMRI) with the categorical n-back task (CN-BT), which maximized demands for executive reasoning while holding memory demands constant. METHODS: A total of 33 drug-naive, right-handed male ADHD without comorbidity (mean age 9.9±2.4 years) and 27 right-handed, healthy male controls (mean age 10.9±2.7 years) were recruited in the present study. Event-related fMRI was used to study differences in brain activity during the CN-BT between the two groups. RESULTS: The two groups did not differ in their accuracy in the CN-BT, although the ADHD patients showed significantly shorter reaction times to correct responses than did the controls. During the CN-BT, both ADHD patients and controls showed significant positive and negative activations by the correct responses, mainly in the sensory-motor pathways and the striato-cerebellum circuit. Additionally, the ADHD patients showed significantly higher activation in the bilateral globus pallidus and the right hippocampus compared with the controls. There was also a positive correlation between hyperactivation of the left globus pallidus and the reaction time to correct responses in ADHD. CONCLUSIONS: In contrast to controls, ADHD patients showed neural hyperactivation in the striatum and mediotemporal areas during a working memory task involving categorization. Hyperfunction in these areas might be the pathophysiological foundation of ADHD, related to the deficits of working memory and the impulsive symptoms.

Trends in the prescribing of psychotropic medications for inpatient children and adolescents, 2000-2010: a study from China.

The objective of this study was to investigate the patterns in prescribing of psychotropic drugs for children and adolescents within the psychiatric department of a general hospital in China. Medical records of 878 patients (0-18 years old) were reviewed in 2000, 2005 and 2010. Patient characteristics, total psychotropic drug use and the proportionate use of each drug class (antipsychotics, antidepressants, mood stabilizers and anxiolytic-hypnotic drugs) were analysed. The results indicated that there was a 19.2% increase in the overall use of psychotropic drugs during the study period. The use of selective serotonin reuptake inhibitors increased from 24.8 to 45%, whereas that of tricyclic antidepressants decreased from 17.7 to 0.5%. The use of second-generation antipsychotics increased from 56 to 80%. In contrast, the use of first-generation antipsychotic decreased from 26.2 to 6.5%. The use of valproate also increased significantly from 2.1 to 16.4%. In patients diagnosed with schizophrenia, the use of selective serotonin reuptake inhibitors increased from 1.2 to 18.9% and that of valproate increased from 0 to 12.6%. The increasing trends in psychotropic drug use necessitate addition research to confirm their safety and efficacy in this specific population.