A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. OBJECTIVE: The aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. METHODS: This 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. RESULTS: Among the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants' average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (ß=-12.203, 95% CI -17.882 to -6.523; P<.001), owing to lower scores on the subscales Inattention (ß=-3.966, 95% CI -6.285 to -1.647; P<.001), Hyperactivity/Impulsivity (ß=-5.735, 95% CI -8.334 to -3.137; P<.001), and Oppositional Defiant Disorder (ß=-2.995, 95% CI -4.857 to -1.132; P=.002). The intervention was associated with significant reduction in the Metacognition Index (ß=-6.312, 95% CI -10.973 to -1.650; P=.006) and Global Executive Composite (ß=-5.952, 95% CI -10.214 to -1.690; P=.003) on the BRIEF. No severe intervention-related adverse events were reported. CONCLUSIONS: This novel digital cognitive-physical intervention was efficacious in school-age children with ADHD. A larger multicenter effectiveness trial with longer follow-up is warranted to confirm these findings and to assess the durability of treatment effects. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2300070521; https://www.chictr.org.cn/showproj.html?proj=177806.

Age-dependent changes in brain iron deposition and volume in deep gray matter nuclei using quantitative susceptibility mapping.

BACKGROUND: Microstructural changes in deep gray matter (DGM) nuclei are related to physiological behavior, cognition, and memory. Therefore, it is critical to study age-dependent trajectories of biomarkers in DGM nuclei for understanding brain development and aging, as well as predicting cognitive or neurodegenerative diseases. OBJECTIVES: We aimed to (1) characterize age-dependent trajectories of mean susceptibility, adjusted volume, and total iron content simultaneously in DGM nuclei using quantitative susceptibility mapping (QSM); (2) examine potential contributions of sex related effects to the different age-dependence trajectories of volume and iron deposition; and (3) evaluate the ability of brain age prediction by combining mean magnetic susceptibility and volume of DGM nuclei. METHODS: Magnetic susceptibilities and volumetric values of DGM nuclei were obtained from 220 healthy participants (aged 10-70 years) scanned on a 3T MRI system. Regions of interest (ROIs) were drawn manually on the QSM images. Univariate regression analysis between age and each of the MRI measurements in a single ROI was performed. Pearson correlation coefficients were calculated between magnetic susceptibility and adjusted volume in a single ROI. The statistical significance of sex differences in age-dependent trajectories of magnetic susceptibilities and adjusted volumes were determined using one-way ANCOVA. Multiple regression analysis was used to evaluate the ability to estimate brain age using a combination of the mean susceptibilities and adjusted volumes in multiple DGM nuclei. RESULTS: Mean susceptibility and total iron content increased linearly, quadratically, or exponentially with age in all six DGM nuclei. Negative linear correlation was observed between adjusted volume and age in the head of the caudate nucleus (CN; R2 = 0.196, p < 0.001). Quadratic relationships were found between adjusted volume and age in the putamen (PUT; R2 = 0.335, p < 0.001), globus pallidus (GP; R2 = 0.062, p = 0.001), and dentate nucleus (DN; R2 = 0.077, p < 0.001). Males had higher mean magnetic susceptibility than females in the PUT (p = 0.001), red nucleus (RN; p = 0.002), and substantia nigra (SN; p < 0.001). Adjusted volumes of the CN (p < 0.001), PUT (p = 0.030), GP (p = 0.007), SN (p = 0.021), and DN (p < 0.001) were higher in females than those in males throughout the entire age range (10-70 years old). The total iron content of females was higher than that of males in the CN (p < 0.001), but lower than that of males in the PUT (p = 0.014) and RN (p = 0.043) throughout the entire age range (10-70 years old). Multiple regression analyses revealed that the combination of the mean susceptibility value of the PUT, and the volumes of the CN and PUT had the strongest associations with brain age (R2 = 0.586). CONCLUSIONS: QSM can be used to simultaneously investigate age- and sex- dependent changes in magnetic susceptibility and volume of DGM nuclei, thus enabling a comprehensive understanding of the developmental trajectories of iron accumulation and volume in DGM nuclei during brain development and aging.

A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.

Shared atypical spontaneous brain activity pattern in early onset schizophrenia and autism spectrum disorders: evidence from cortical surface-based analysis.

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD.

Brain controllability and morphometry similarity of internet gaming addiction.

Internet gaming addiction (IGD) is a common disease in teenagers which usually reflects the abnormalities in brain function or structure. Several computational models have been applied to investigate the characteristic of IGD brain networks, for instance, the conception of brain controllability. The primary objective of this study was to explore the relationship between brain controllability and IGD related clinical behaviour. A sample of 101 subjects, including 49 IGD patients and 52 normal controls, were recruited to undergo MR T1 and DTI scanning. Specifically, the MR images were used to generate the white matter connectivity matrix and the morphometry similarity network. The morphometry similarity network was then divided into several communities using modular decomposition. After, average controllability, modal controllability and synchronizability were calculated through measuring the adjacency matrix. The results indicated that the IGD group had greater synchronizability and modal controllability compared to that of the control group, and different morphological-based brain communities had different controllability properties. Furthermore, the addiction demonstrated the mediating effects between nodal or modular brain controllability as well as anxiety. In conclusion, brain controllability could be a potential biomarker of IGD.

A novel school-based approach to screening for attention deficit hyperactivity disorder.

Current approaches to screening for ADHD result in high rates of false positives. A proof of concept study to investigate the added benefits in the school-based detection of ADHD of adding a standardised teacher to teacher interview to traditional parent and teacher report questionnaires. A school-based study of diagnostic accuracy of ADHD using a novel 2-stage screening process. Participants were all 1026 pupils enrolled in grades 1 to 6 (ages 6-12 years) of a school in Hunan Province, China. The primary outcome was a diagnosis of ADHD on the Kiddie Schedule for Affective Disorders and Schizophrenia Present Lifetime version. 230 (22.4%) of the 1026 students screened positive at Stage 1 (parent and teacher questionnaires) (Sensitivity 0.86 [95% CI, 0.75 to 0.96], specificity 0.80 [95% CI, 0.78-0.83], false positive rate 0.20 (95% CI, 0.18 to 0.23), false negative rate was 0.14 (95% CI, 0.12 to 0.16). 65 remained screen-positive at the Stage 2 screen (teacher to teacher SNAP-IV interview). 36/65 (55.4%) of these Stage 2 screen positive participants and 1/144 (0.7%) of the screen negative subjects met DSM-IV criteria for ADHD (sensitivity 0.83 [95% CI, 0.71-0.95]; specificity of 0.97 [95% CI, 0.96-0.98]; false positive rate 0.03 [95% CI, 0.01 to 0.04], false negative rate 0.16 [95% CI, 0.15 to 0.19]. Adding teacher to teacher interviews to traditional questionnaire-based screening has the potential to improve the clinical utility of school-based screening for ADHD reducing the proportion of false positives, without a negative impact on sensitivity.

MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced ß-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene-circuit-behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2 However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders.

BACKGROUND: About 20-40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon. METHODS: A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low-density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents. RESULTS: Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors. CONCLUSIONS: Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

Altered Functional Connectivity in Children with ADHD Revealed by Scalp EEG: An ERP Study.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental brain disorders in childhood. Despite extensive researches, the neurobiological mechanism underlying ADHD is still left unveiled. Since the deficit functions, such as attention, have been demonstrated in ADHD, in our present study, based on the oddball P3 task, the corresponding electroencephalogram (EEG) of both healthy controls (HCs) and ADHD children was first collected. And we then not only focused on the event-related potential (ERP) evoked during tasks but also investigated related brain networks. Although an insignificant difference in behavior was found between the HCs and ADHD children, significant electrophysiological differences were found in both ERPs and brain networks. In detail, the dysfunctional attention occurred during the early stage of the designed task; as compared to HCs, the reduced P2 and N2 amplitudes in ADHD children were found, and the atypical information interaction might further underpin such a deficit. On the one hand, when investigating the cortical activity, HCs recruited much stronger brain activity mainly in the temporal and frontal regions, compared to ADHD children; on the other hand, the brain network showed atypical enhanced long-range connectivity between the frontal and occipital lobes but attenuated connectivity among frontal, parietal, and temporal lobes in ADHD children. We hope that the findings in this study may be instructive for the understanding of cognitive processing in children with ADHD.

De novo variants in the Helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth.

CHD8, which encodes Chromodomain helicase DNA-binding protein 8, is one of a few well-established Autism Spectrum Disorder (ASD) genes. Over 60 mutations have been reported in subjects with variable phenotypes, but little is known concerning genotype-phenotype correlations. We have identified four novel de novo mutations in Chinese subjects: two nonsense variants (c.3562C>T/p.Arg1188X, c.2065C>A/p.Glu689X), a splice site variant (c.4818-1G>A) and a missense variant (c.3502T>A/p.Tyr1168Asn). Three of these were identified from a 445-member ASD cohort by ASD gene panel sequencing of the 96 subjects who remained negative after molecular testing for copy number variation, Rett syndrome, FragileX and tuberous sclerosis complex (TSC). The fourth (p.Glu689X) was detected separately by diagnostic trio exome sequencing. We used diagnostic instruments and a comprehensive review of phenotypes, including prenatal and postnatal growth parameters, developmental milestones, and dysmorphic features to compare these four subjects. In addition to autism, they also presented with prenatal onset macrocephaly, intellectual disability, overgrowth during puberty, sleep disorder, and dysmorphic features, including broad forehead with prominent supraorbital ridges, flat nasal bridge, telecanthus and large ears. For further comparison, we compiled a comprehensive list of CHD8 variants from the literature and databases, which revealed constitutive and somatic truncating variants in the HELIC (Helicase-C) domain in ASD and in cancer patients, respectively, but not in the general population. Furthermore, HELIC domain mutations were associated with a severe phenotype defined by a greater number of clinical features, lower verbal IQ, and a prominent, consistent pattern of overgrowth as measured by weight, height and head circumference. Overall, this study adds to the ASD-associated loss-of-function mutations in CHD8 and highlights the clinical importance of the HELIC domain of CHD8.

Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease.

BACKGROUND: Currently, no study has evaluated metal accumulation in the brains of patients with Wilson's disease by using quantitative susceptibility mapping at 3T MRI. The objectives of this study were to qualitatively and quantitatively evaluate changes in magnetic susceptibility and R2* maps in deep gray matter nuclei to discriminate Wilson's disease patients from healthy controls and to evaluate their sensitivities in diagnosing Wilson's disease. METHODS: Magnetic susceptibility and R2* maps and conventional T1-weighted, T2-weighted, and T2-weighted fluid-attenuated inversion recovery images were obtained from 17 Wilson's disease patients and 14 age-matched healthy controls on a 3T MRI scanner. Differences between Wilson's disease and healthy control groups in susceptibility and R2* values in multiple deep nuclei were evaluated using a Mann-Whitney U test and receiver operating characteristic curves. The correlations of susceptibility and R2* values with Unified Wilson's Disease Rating Scale score were also performed. RESULTS: Magnetic susceptibility and R2* can effectively distinguish different types of signal abnormalities. Magnetic susceptibility and R2* values in multiple deep nuclei of Wilson's disease patients were significantly higher than those in healthy controls. Magnetic susceptibility value in the substantia nigra had the highest area under the curve (0.888). There were positive correlations of the Unified Wilson's Disease Rating Scale score with susceptibility values in the caudate nucleus (r = 0.757, P = 0.011), putamen (r = 0.679, P = 0.031), and red nucleus (r = 0.638, P = 0.047), as well as R2* values in the caudate nucleus (r = 0.754, P = 0.012). CONCLUSIONS: Quantitative susceptibility mapping at 3T could be a useful tool to evaluate metal accumulation in deep gray matter nuclei of Wilson's disease patients. © 2020 International Parkinson and Movement Disorder Society.

The critical role of ASD-related gene CNTNAP3 in regulating synaptic development and social behavior in mice.

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

Resting-state brain activity in Chinese boys with low functioning autism spectrum disorder.

BACKGROUND: This study aimed to explore the resting-state fMRI changes in Chinese boys with low functioning autism spectrum disorder (LFASD) and the correlation with clinical symptoms. METHODS: The current study acquired resting-state fMRI data from 15 Chinese boys with LFASD and 15 typically developing (TD) boys to examine the local brain activity using the regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) indexes; the researchers also examined these measures and their possible relationships with clinical symptoms using the autism behavior checklist. RESULTS: Results indicated that boys with LFASD exhibited increased ReHo in the right precuneus and inferior parietal gyrus (IPG), increased ALFF in right middle temporal gyrus, angular gyrus and IPG. However, no correlation was found between the ALFF/ReHo score and clinical symptoms in the LFASD group. CONCLUSIONS: Some of the brain regions had ReHo/ALFF values that were higher in the boys with LFASD than the TD group and these differentiated brain areas in boys with LFASD were all on the right cerebrum, which supported 'atypical rightward asymmetry' in boys with LFASD.

Difference in the functional connectivity of the dorsolateral prefrontal cortex between smokers with nicotine dependence and individuals with internet gaming disorder.

BACKGROUND: It has been reported that internet gaming disorder (IGD) and smokers with nicotine dependence (SND) share clinical characteristics, such as over-engagement despite negative consequences and cravings. This study is to investigate the alterations in the resting-state functional connectivity (rsFC) of the dorsolateral prefrontal cortex (DLPFC) observed in SND and IGD. In this study, 27 IGD, 29 SND, and 33 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. DLPFC connectivity was determined in all participates by investigating the synchronized low-frequency fMRI signal fluctuations using a temporal seed-based correlation method. RESULTS: Compared with the HC group, the IGD and SND groups showed decreased rsFC with DLPFC in the right insula and left inferior frontal gyrus with DLPFC. Compared with SND group, the IGD subjects exhibited increased rsFC in the left inferior temporal gyrus and right inferior orbital frontal gyrus and decreased rsFC in the right middle occipital gyrus, supramarginal gyrus, and cuneus with DLPFC. CONCLUSION: Our results confirmed that SND and IGD share similar neural mechanisms related to craving and impulsive inhibitions. The significant difference in rsFC with DLPFC between the IGD and SND subjects may be attributed to the visual and auditory stimulation generated by long-term internet gaming.

Assessment of in vivo microstructure alterations in gray matter using DKI in Internet gaming addiction.

BACKGROUND: The aim of the current study was to investigate the utility of diffusional kurtosis imaging (DKI) in the detection of gray matter (GM) alterations in people suffering from Internet Gaming Addiction (IGA). METHODS: DKI was applied to 18 subjects with IGA and to 21 healthy controls (HC). Whole-brain voxel-based analyses were performed with the following derived parameters: mean kurtosis metrics (MK), radial kurtosis (K⊥), and axial kurtosis (K//). A significance threshold was set at P <0.05, AlphaSim corrected. Pearson's correlation was performed to investigate the correlations between the Chen Internet Addiction Scale (CIAS) and the DKI-derived metrics of regions that differed between groups. Additionally, we used voxel-based morphometry (VBM) to detect GM-volume differences between the two groups. RESULTS: Compared with the HC group, the IGA group demonstrated diffusional kurtosis parameters that were significantly less in GM of the right anterolateral cerebellum, right inferior and superior temporal gyri, right supplementary motor area, middle occipital gyrus, right precuneus, postcentral gyrus, right inferior frontal gyrus, left lateral lingual gyrus, left paracentral lobule, left anterior cingulate cortex, and median cingulate cortex. The bilateral fusiform gyrus, insula, posterior cingulate cortex (PCC), and thalamus also exhibited less diffusional kurtosis in the IGA group. MK in the left PCC and K⊥ in the right PCC were positively correlated with CIAS scores. VBM showed that IGA subjects had higher GM volume in the right inferior and middle temporal gyri, and right parahippocampal gyrus, and lower GM volume in the left precentral gyrus. CONCLUSIONS: The lower diffusional kurtosis parameters in IGA suggest multiple differences in brain microstructure, which may contribute to the underlying pathophysiology of IGA. DKI may provide sensitive imaging biomarkers for assessing IGA severity.

Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

BACKGROUND: Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. METHODS: Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. RESULTS: There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. CONCLUSIONS: Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.

Identification of ANKK1 rs1800497 variant in schizophrenia: new data and meta-analysis.

One functional polymorphism (rs1800497) within the ankyrin repeat and kinase domain containing-1 gene (ANKK1) was reported to be associated with schizophrenia, but results among different studies vary and conclusions remain controversial. The present study sought to clarify this potential association among a population of Han Chinese with early onset schizophrenia using a case-control (396 patients and 399 controls) and family based study (103 trios). We then performed a meta-analysis (comprising 11 case-control and 2 family-based studies) based on the present literature. Results of the association study revealed no significant difference in allele and genotype frequencies between the cases and controls, and no significant transmission distortion was detected. Kaplan-Meier survival analysis showed that age at onset in schizophrenia was significantly associated with the rs1800497 polymorphism in female patients, but not in males. Female T allele carriers had a lower age at onset than those without T allele (log rank statistic χ(2) = 5.16, P = 0.023; corrected P = 0.046). Meta-analysis results indicated that rs1800497 is not associated with schizophrenia in the overall population (P = 0.77 for the case-control studies; P = 0.06 for the family-based studies). Our results support the hypothesis that rs1800497 polymorphism is likely to have a modifying rather than causative effect on schizophrenia. These findings may represent a significant genetic clue for the etiology of schizophrenia in females, but further investigation is required to clarify the exact role of ANKK1 in the development of schizophrenia.

Clonidine Patch for Tourette Syndrome With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). METHODS: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. RESULTS: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. CONCLUSION: Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.