EGR1 Regulates SHANK3 Transcription at Different Stages of Brain Development.

The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. In this study, we employed immunofluorescence to examine the expression of SHANK3 in brain organoids at various stages. Our results revealed elevated levels of SHANK3 expression in brain-like organoids at Day 60. Additionally, we utilized bioinformatics software to predict and analyze the SHANK3 gene's transcription start site. Through the dual luciferase reporter gene technique, we identified core transcription elements within the SHANK3 promoter. Site-directed mutations were used to identify specific transcription sites of SHANK3. To determine the physical binding of potential transcription factors to the SHANK3 promoter, we employed electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy.

Behavior Management Training for Parents of Children with Preschool ADHD Based on Parent-Child Interactions: A Multicenter Randomized Controlled, Follow-Up Study.

Objective: There is a need to develop optimized, evidence-based parent training programs tailored for preschoolers with attention deficit hyperactivity disorder (ADHD). The objective of this study was to explore a behavioral management training program aimed at the parents of preschool children with ADHD, which directly analyzes parent-child interaction from the perspective of system theory, and the intervention effect on ADHD in preschool children. Methods: A multicenter randomized controlled study was conducted using system-based group therapy with 62 parents of preschool children with ADHD aged four to six years. ADHD symptoms, behavioral and emotional problems, and social functioning were compared with 61 control children whose parents did not receive training by applying the ADHD Rating Scale (ADHD-RS), Strengths and Difficulties Questionnaire (SDQ), and Questionnaire-Children with Difficulties (QCD) at the time of subject entry and at two and six months of entry, respectively. Results: The results of the ADHD-RS assessment showed that children in the intervention group had significantly lower factor scores for attention deficit, hyperactivity, and impulsivity than the children in the control group after parental training and at follow-up (P < 0.05). Total scores on the SDQ scale, as well as character problems, hyperactivity, and peer interaction scores, significantly decreased with statistically significant differences (all P < 0.05), and emotional symptoms and prosocial behavior did not notable decline (P > 0.05). Compared with the control group, the total scores of the QCD scale and the scores of each factor in the intervention group remained significantly higher at the follow-up (P < 0.05). Conclusion: After continuous intervention for eight weeks, parents were able to help the children with preschool ADHD to improve their ADHD symptoms and emotional behavioral and social functioning significantly, and the efficacy was maintained at the four-month follow-up; the systemic-based parent training in behavior management (PTBM) is applicable to the treatment of preschool ADHD and is worth promoting.

Identification of adolescent patients with depression via assessment of the niacin skin flushing response.

BACKGROUND: Depressive disorder (DD) affects approximately 20 % of adolescents worldwide, but it is underdiagnosed due to the lack of objective biomarkers. Niacin skin flushing response (NSFR) is an objective and noninvasive biomarker of adult depression; however, its effectiveness has not been assessed in adolescents. METHODS: This study included 198 adolescents with 50 % healthy controls (HC). Linear mixed-effects model and multiple linear regression analyses were performed to assess differences in NSFR between the DD and HC groups. Logistic regression models based on NSFR were constructed, and the area under curve (AUC) was calculated to evaluate the performance of models. Spearman correlations were calculated to assess the relationships between NSFR and disease duration and hormone levels associated with puberty. RESULTS: Adolescents with DD displayed significantly attenuated and delayed NSFR compared to HC. NSFR effectively distinguished DD patients from HC with AUC values of 0.719 (sensitivity = 0.844) and 0.721 (sensitivity = 0.829) determined in the discovery and validation sets, respectively. Within the DD group, the maximum degree of NSFR was negatively correlated with the disease duration (r = -0.28, p = 0.011), and the overall degree of NSFR was positively associated with prolactin (r = 0.29, p = 0.039) and thyroxine (r = 0.29, p = 0.027) levels. LIMITATIONS: Future investigations will be necessary to confirm our results in an independent sample set. CONCLUSIONS: This study provides the first evidence of the utility of NSFR as an objective auxiliary diagnostic biomarker for adolescent depression. It provides new clues to understand the pathophysiology of the disease, and helps promote precise diagnosis, treatment, and prognostic evaluation of adolescent depression.

Supplementation With Zinc Proteinate Increases the Growth Performance by Reducing the Incidence of Diarrhea and Improving the Immune Function of Dairy Calves During the First Month of Life.

Two experiments were conducted to identify the optimal dose of zinc proteinate (ZP) in the diet for dairy calves and then to compare early supplementation with the ZP or zinc methionine (ZM) on the growth performance, incidence of diarrhea, antioxidant status, and immune function of dairy calves during their first month of life. In Experiment 1, forty newborn female Holstein dairy calves were randomly divided into four groups (n = 10): a control group (without ZP supplementation, ZP0) or groups that received ZP supplementation at 40, 80, and 120 mg zinc/day, respectively (ZP40, ZP80, and ZP120). The experiment lasted 14 days, and the growth performance, incidence of diarrhea, and serum zinc concentration were analyzed. In Experiment 2, thirty-six newborn female Holstein dairy calves were randomly allocated to three groups (n = 12): a negative control group (without zinc supplementation, CON), a positive control group (supplemented with 80 mg zinc/day in the form of zinc methionine, ZM), and a ZP group (supplemented with 80 mg zinc/day in the form of ZP). The experiment lasted 28 days, and the growth performance, incidence of diarrhea, serum zinc concentration, serum antioxidant indicators, and concentrations of plasma immunoglobulins and cytokines were determined on days 7, 14, 21, and 28. Results showed that in Experiment 1, supplementation with ZP to yield 80 mg zinc/day increased the ADG (P < 0.01) and serum zinc concentration (P < 0.01), and decreased the F/G (P < 0.01) and the incidence of diarrhea (P < 0.05) during days 1-14. In Experiment 2, compared with the CON group, ZP increased the ADG (P < 0.01), serum zinc concentration (P < 0.01), and plasma immunoglobulin G (IgG; P < 0.01) and IgM (P < 0.01) concentrations, but reduced the incidence of diarrhea (P < 0.01), serum malondialdehyde (P < 0.01), and plasma interleukin-1ß (P < 0.01) concentrations during days 1-28. Overall, ZP supplementation to yield 80 mg zinc/day improves the growth performance and immune function, and decrease the incidence of diarrhea of dairy calves, which was comparable to the same dose of zinc in the form of ZM.

Novel Process Methods for the Whole Cottonseed: Effect on the Digestibility, Productivity, Fat Profile, and Milk Gossypol Levels in Lactating Dairy Cows.

In this study, we aimed to determine the effect of mixed-process methods on the ruminal degradability of whole cottonseed (WCS) both in situ and in vitro, and the effect on the production performance of dairy cows. Eight WCS process methods were tested on the ruminal digestibility, including crush-alkali 1 (CA1), crush-alkali 2 (CA2), crush-alkali 3 (CA3), alkali 1-crush (A1C), alkali 2-crush (A2C), alkali 3-crush (A3C), crush-only (CO), and non-processed. Alkali 1, 2, and 3 indicate the supplementation of alkali to WCS at the dose of 4% on dry matter (DM) base as followed: 4% NaOH, 2% NaOH + 2% CaO, and 2% NaOH + 2% CaCl2 alkaline, respectively. Among all treatments, CA2 showed the highest WCS ruminal degradation in situ and the highest intestinal digestibility of WCS in vitro. Furthermore, an animal experiment was conducted for 60 days on 30 Holstein dairy cows, using a diet without WCS (CON group), a diet containing 8% non-processed WCS (NP group), and a diet containing 8% CA2-treated WCS (CA2 group). The results indicated that the dry matter intake, 4% fat-corrected milk production, milk protein, milk fat, and content of short-chain saturated fatty acid of milk in the CA2 group were significantly higher (P < 0.05) than CON group. Furthermore, DMI, the CLA was significantly greater (P < 0.05) in the CA2 group than the other groups. Additionally, the free gossypol concentration in serum or milk was under safety level in the three groups. Overall, crush and alkalization (NaOH: CaO = 1:1) treatment could improve the utilization of WCS in dairy farms.

Comparison of clinical characteristics and treatment efficacy in childhood-onset schizophrenia and adolescent-onset schizophrenia in mainland China: A retrospective study.

AIM: The comparative study of childhood-onset schizophrenia (COS) and adolescent-onset schizophrenia (AOS) is scarce. This study aimed to examine the differences in clinical presentations and treatment efficacy between COS and AOS and further analyse the factors affecting the efficacy of early-onset schizophrenia (EOS). METHODS: A total of 582 electronic medical records of inpatients with EOS (216 COS and 366 AOS inpatients) between 2012 and 2019 were retrospectively analysed. The positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms. Logistic regression analysis was performed to analyse the predictors of efficacy. RESULTS: The mean age of onset of EOS was 12.87 ± 2.19 years. The importance of better diagnosing COS appeared in a longer illness course, more frequently insidious onset, less frequent delusions, more severe negative symptoms and bizarre behaviours than AOS. Besides, COS had more frequent visual hallucinations and impulsive behaviours than AOS. After hospitalization, the improvement rate of psychotic symptoms in COS and AOS were 38.3% and 47.8%, respectively. The difference of efficacy between the two groups was statistically significant. Days of hospitalization, age of onset, presence of flat affect, PANSS total and negative score at admission were predictors of treatment efficacy in EOS individuals. CONCLUSIONS: COS inpatients suffer more obvious negative symptoms, bizarre behaviours, visual hallucinations and impulsive behaviours and worse efficacy than AOS inpatients. The severity of negative symptoms and age of onset seem the most noteworthy predictors of efficacy. These findings highlight the importance of early detection and early intervention.

Longitudinal Study of Brain Asymmetries in Autism and Developmental Delays Aged 2-5 Years.

Some previous studies have demonstrated atypical brain lateralization in autism spectrum disorder (ASD). However, most of these reports have focused on language-related asymmetries in adults, and the developmental trajectory of hemispheric asymmetries in the important phase that occurs at 2-5 years of age remains unclear. Thus, we used structural magnetic resonance imaging and diffusion tensor imaging (DTI) in a longitudinal study of grey matter (GM) asymmetries across all cortical parcellation units (PUs) and white matter (WM) lateralization across the WM skeleton using voxel-based morphometry and tract-based spatial statistics (TBSS) in 34 toddlers with ASD and a matched group of 26 toddlers with developmental delay (DD) at 2-3 years old and with follow-up at 4-5 years of age. We found the total brain volume and fractional anisotropy (FA) of WM was higher in the ASD group than in the DD group at baseline and 2 years later. The ASD and DD groups showed a rightward asymmetry in a large number of cortical PUs and in the WM skeleton at both time points. GM lateralization was associated with the social and communicative disturbances observed in ASD at baseline, while WM asymmetry was significantly related to social disturbances and repetitive behaviours seen at 4-5 years of age. In conclusion, both ASD and DD toddlers had widespread rightward asymmetry, and the patterns of lateralization were similar across the groups. GM and WM showed asynchronous development of hemispheric asymmetries at 2-5 years of age, and this lateralization was associated with ASD symptoms.

Structural networks in children with autism spectrum disorder with regression: A graph theory study.

BACKGROUND: Regression is frequently described in Autism spectrum disorder (ASD). Limited comprehensive studies have been conducted in patients with ASD with regression. PURPOSE: To explore the network topological properties in ASD children with (ASD-R) and without (ASD-NR) regression. METHODS: In this study, 29 ASD-R, 68 ASD-NR, and 40 children with developmental delay (DD) were recruited. We utilized graph theory to characterize the white matter structure networks by using diffusion tensor imaging and T1-weighted imaging on a 3-T magnetic resonance system. Statistical analyses were performed using IBM SPSS (version 23). RESULTS: ANCOVA showed significant differences in global efficiency, characteristic path length and sigma among the ASD-R, ASD-NR and DD groups, but the difference was not significant between the ASD-R and ASD-NR groups. There were 10 common hubs based on regional degree and regional efficiency in all groups. The hubness of the left superior frontal gyrus-dorsolateral, left middle occipital gyrus and right precuneus were enhanced (by regional degree) and that of the right thalamus was reduced (by regional efficiency) in the ASD-R relative to the ASD-NR group. After controlling for the course of regression, the CARS scores were significantly correlated with the regional efficiency of the right precuneus in the ASD-R group. CONCLUSIONS: The ASD-R children were different from the ASD-NR children in the distribution of hub regions, although there were no global network property differences between them. In ASD-R children, the right precuneus (PCUN.R) might play an important role and relate to autism symptom severity.

Anomalies in uncinate fasciculus development and social defects in preschoolers with autism spectrum disorder.

BACKGROUND: Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulties in emotional regulation. The neural substrates for these socio-affective deficits are not yet clear, but one potential candidate is maldevelopment of the uncinate fasciculus (UF), a white matter tract thought to be involved in socio-affective processing. However, the developmental trajectory of the UF in young children with social interaction deficits has not been examined. The present study was designed to describe the developmental growth trajectory of the UF and the relationships between UF development and social deficits in ASD. METHODS: Eigenvalues of the UF were measured by diffusion tensor imaging (DTI)-based tractography in 37 children with ASD and 27 matched 2-3-year-old subjects with developmental delay (DD) at baseline (time 1) and at 2-year follow-up (time 2). Growth rates of the UF were compared between groups and associations with social deficit scores according to the Autism Diagnostic Interview-Revised (ADI-R) analyzed by Pearson's correlations. RESULTS: At time 1, axial diffusivity (AD) of the left UF was significantly larger in the ASD group than the DD group. At time 2, left UF fractional anisotropy (FA) was significantly higher and radial diffusivity (RD) significantly lower in the ASD group than the DD group. The rate of UF growth during this 2-year interval was faster in children with ASD than DD. Significant negative correlations were found between the rise in ADI-R social deficit measures and both right UF RD and left UF mean diffusivity (MD). CONCLUSIONS: Young children with ASD demonstrate UF overgrowth during the 2-year development period between 2 and 3 and 4-5 years of age, and this white matter abnormality is directly associated with the progression of social deficits. TRIAL REGISTRATION: World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.

Exploring the relationship between fairness and 'brain types' in children with high-functioning autism spectrum disorder.

BACKGROUND: Existing research typically focuses on only one domain of cognition with regard to fairness-theory of mind or executive function. However, children with High-functioning autism spectrum disorder (HF-ASD) are cognitively impaired in both domains. Moreover, little is known about fairness characteristics in children with HF-ASD in relation to both domains of cognition. METHODS: Thirty children with HF-ASD as well as 39 children with typical development (TD) were evaluated in this study. We investigated the development of children's fairness characteristics as a responder in a mini ultimatum game (UG). The different 'brain types,' i.e., with or without HF-ASD, were evaluated using the Empathy Questionnaire-Systemizing Questionnaire (E/SC-Q). Furthermore, we explored the relationship between fairness and brain types using Pearson correlation analyses. RESULTS: Children in the HF-ASD group were more likely to accept unfair offers than were children in the TD group (χ2 = 17.513, p = .025). In the HF-ASD group, the acceptance rate of unfair offers was correlated with the discrepancy score (r = 0.363, p = .048), while there were no significant correlations in the TD group. In HF-ASD group, compared with Type S, acceptance rate of unfair offer was significant higher in Extreme Type S 'brain type' (F = 28.584, p < .001). While dividing TD participants by 'brain type', there was no significant difference in acceptance rate of unfair offer among five difference 'brain types' (F = 1.131, p = .358). Stepwise regression revealed that Extreme Type S positively predicted acceptance of unfair offers (F [1, 68] = 8.695, p < .001). DISCUSSION: Our findings show that children with HF-ASD were more likely to accept an unfair offer; in particular, the more unbalanced the development of empathy and systemizing was, the more significant the unfairness preference observed. Extreme Type S positively predicted the acceptance of unfair offers by children with HF-ASD. REGISTRATION OF CLINICAL TRIALS: World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.

Shifts of Hydrogen Metabolism From Methanogenesis to Propionate Production in Response to Replacement of Forage Fiber With Non-forage Fiber Sources in Diets in vitro.

The rumen microbial complex adaptive mechanism invalidates various methane (CH4) mitigation strategies. Shifting the hydrogen flow toward alternative electron acceptors, such as propionate, was considered to be a meaningful mitigation strategy. A completely randomized design was applied in in vitro incubation to investigate the effects of replacing forage fiber with non-forage fiber sources (NFFS) in diets on methanogenesis, hydrogen metabolism, propionate production and the methanogenic and bacterial community. There are two treatments in the current study, CON (a basic total mixed ration) and TRT (a modified total mixed ration). The dietary treatments were achieved by partly replacing forage fiber with NFFS (wheat bran and soybean hull) to decrease forage neutral detergent fiber (fNDF) content from 24.0 to 15.8%, with the composition and inclusion rate of other dietary ingredients remaining the same in total mixed rations. The concentrations of CH4, hydrogen (H2) and volatile fatty acids were determined using a gas chromatograph. The archaeal and bacterial 16S rRNA genes were sequenced by Miseq high-throughput sequencing and used to reveal the relative abundance of methanogenic and bacterial communities. The results revealed that the concentration of propionate was significantly increased, while the concentration of acetate and the acetate to propionate ratio were not affected by treatments. Compared with CON, the production of H2 increased by 8.45% and the production of CH4 decreased by 14.06%. The relative abundance of Methanomassiliicoccus was significantly increased, but the relative abundance of Methanobrevibacter tended to decrease in TRT group. At the bacterial phylum level, the TRT group significantly decreased the relative abundance of Firmicutes and tended to increase the relative abundance of Bacteroidetes. The replacement of forage fiber with NFFS in diets can affect methanogenesis by shifting the hydrogen flow toward propionate, and part is directed to H2 in vitro. The shift was achieved by a substitution of Firmicutes by Bacteroidetes, another substitution of Methanobrevibacter by Methanomassiliicoccus. Theoretical predictions of displacements of H2 metabolism from methanogenesis to propionate production was supported by the dietary intervention in vitro.

Alterations in hub organization in the white matter structural network in toddlers with autism spectrum disorder: A 2-year follow-up study.

Little is currently known about the longitudinal developmental patterns of hubs in the whole-brain white matter (WM) structural networks among toddlers with autism spectrum disorder (ASD). This study utilized diffusion tensor imaging (DTI) and deterministic tractography to map the WM structural networks in 37 ASD toddlers and 27 age-, gender- and developmental quotient-matched controls with developmental delay (DD) toddlers aged 2-3 years old at baseline (Time 1) and at 2-year follow-up (Time 2). Furthermore, graph-theoretical methods were applied to investigate alterations in the network hubs in these patients at the two time points. The results showed that after 2 years, 17 hubs were identified in the ASD subjects compared to the controls, including 13 hubs that had not changed from baseline and 4 hubs that were newly identified. In addition, alterations in the properties of the hubs of the right middle frontal gyrus, right insula, left median cingulate gyri, and bilateral precuneus were significantly correlated with alterations in the behavioral data for ASD patients. These results indicated that at the stage of 2-5 years of age, ASD children showed distributions of network hubs that were relatively stable, with minor differences. Abnormal developmental patterns in the five areas mentioned above in ASD may contribute to abnormalities in the social and nonsocial characteristics of this disorder. Autism Res 2018, 11: 1218-1228. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This work studied the longitudinal developmental patterns of hubs in the whole-brain white matter (WM) structural network among toddlers with autism spectrum disorder (ASD). The findings of this study could have implications for understanding how the abnormalities in hub organization in ASD account for behavioral deficits in patients and may provide potential biomarkers for disease diagnosis and the subsequent monitoring of progression and treatment effects for patients with ASD.

A Fiber Tractography Study of Social-Emotional Related Fiber Tracts in Children and Adolescents with Autism Spectrum Disorder.

The symptoms of autism spectrum disorder (ASD) have been hypothesized to be caused by changes in brain connectivity. From the clinical perspective, the "disconnectivity" hypothesis has been used to explain characteristic impairments in "socio-emotional" function. Therefore, in this study we compared the facial emotional recognition (FER) feature and the integrity of social-emotional-related white-matter tracts between children and adolescents with high-functioning ASD (HFA) and their typically developing (TD) counterparts. The correlation between the two factors was explored to find out if impairment of the white-matter tracts is the neural basis of social-emotional disorders. Compared with the TD group, FER was significantly impaired and the fractional anisotropy value of the right cingulate fasciculus was increased in the HFA group (P < 0.01). In conclusion, the FER function of children and adolescents with HFA was impaired and the microstructure of the cingulate fasciculus had abnormalities.

Autism spectrum disorder as early neurodevelopmental disorder: evidence from the brain imaging abnormalities in 2-3 years old toddlers.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2-3 years old toddlers.

Response inhibition impairment in high functioning autism and attention deficit hyperactivity disorder: evidence from near-infrared spectroscopy data.

BACKGROUND: Response inhibition, an important domain of executive function (EF), involves the ability to suppress irrelevant or interfering information and impulses. Previous studies have shown impairment of response inhibition in high functioning autism (HFA) and attention deficit hyperactivity disorder (ADHD), but more recent findings have been inconsistent. To date, almost no studies have been conducted using functional imaging techniques to directly compare inhibitory control between children with HFA and those with ADHD. METHOD: Nineteen children with HFA, 16 age- and intelligence quotient (IQ)-matched children with ADHD, and 16 typically developing (TD) children were imaged using functional near-infrared spectroscopy (NIRS) while performing Go/No-go and Stroop tasks. RESULTS: Compared with the TD group, children in both the HFA and ADHD groups took more time to respond during the No-go blocks, with reaction time longest for HFA and shortest for TD. Children in the HFA and ADHD groups also made a greater number of reaction errors in the No-go blocks than those in the TD group. During the Stroop task, there were no significant differences between these three groups in reaction time and omission errors. Both the HFA and ADHD groups showed a higher level of inactivation in the right prefrontal cortex (PFC) during the No-go blocks, relative to the TD group. However, no significant differences were found between groups in the levels of oxyhemoglobin concentration in the PFC during the Stroop task. CONCLUSION: Functional brain imaging using NIRS showed reduced activation in the right PFC in children with HFA or ADHD during an inhibition task, indicating that inhibitory dysfunction is a shared feature of both HFA and ADHD.

Single nucleotide polymorphisms predict symptom severity of autism spectrum disorder.

Autism is widely believed to be a heterogeneous disorder; diagnosis is currently based solely on clinical criteria, although genetic, as well as environmental, influences are thought to be prominent factors in the etiology of most forms of autism. Our goal is to determine whether a predictive model based on single-nucleotide polymorphisms (SNPs) can predict symptom severity of autism spectrum disorder (ASD). We divided 118 ASD children into a mild/moderate autism group (n = 65) and a severe autism group (n = 53), based on the Childhood Autism Rating Scale (CARS). For each child, we obtained 29 SNPs of 9 ASD-related genes. To generate predictive models, we employed three machine-learning techniques: decision stumps (DSs), alternating decision trees (ADTrees), and FlexTrees. DS and FlexTree generated modestly better classifiers, with accuracy = 67%, sensitivity = 0.88 and specificity = 0.42. The SNP rs878960 in GABRB3 was selected by all models, and was related associated with CARS assessment. Our results suggest that SNPs have the potential to offer accurate classification of ASD symptom severity.

Family dynamics in families with children with Attention Deficit Hyperactivity Disorder.

BACKGROUND: Development of adjunctive family therapy for the treatment of children with Attention Deficit Hyperactivity Disorder (ADHD) in China requires a detailed understanding of the family dynamics of these families. AIM: Assess the family dynamics of families with children who have ADHD in Nanjing, China. METHODS: Forty-six children 10 to 17 years of age treated at the Nanjing Brain Hospital for ADHD and 46 control children of the same age and gender from schools in Nanjing completed the 19-item Questionnaire of Systematic Family Dynamics (QSFD) which assesses four dimensions of family functioning: Family Atmosphere, Individuation, Moral Absolutism, and Personal Responsibility for Psychological Problems. RESULTS: There were no differences between groups in the perceived causes of psychological problems but the ADHD children reported a poorer family atmosphere, less independence from parents, and more ambiguity about 'right' and 'wrong' in the family. After adjustment for the potential confounding effects of parental education and family economic status, the findings of poorer family atmosphere and less individuation in the ADHD children remained statistically significant. The internal consistency of the four dimensions of the QSFD as completed by the children were poor (alpha=0.44-0.53). CONCLUSION: This preliminary study on the family dynamics of families with children that have ADHD finds that the ADHD children report a poor family atmosphere and little independence from parents. Further work is needed to validate the methods for assessing family dynamics in Chinese families, particularly when using children as informants, but this method provides valuable information that could be used as the focus of adjunctive family therapy to augment the traditional pharmacological and behavioral approaches to the treatment of ADHD.

Detecting abnormalities of corpus callosum connectivity in autism using magnetic resonance imaging and diffusion tensor tractography.

The corpus callosum (CC) has emerged as one of the primary targets of autism research. To detect aberrant CC interhemispheric connectivity in autism, we performed T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)-based tractography in 18 children with high functioning autism (HFA) and 16 well-matched typically developing (TD) children. We compared global and regional T1 measures (CC volume, and CC density), and the DTI measures [fractional anisotropy (FA), apparent diffusion coefficient (ADC), average fiber length (AFL), and fiber number (FN)] of transcallosal fibers, between the two groups. We also evaluated the relationships between scores on the Childhood Autism Rating Scale (CARS) and CC T1 or DTI measurements. Significantly less white matter density in the anterior third of the CC, and higher ADC and lower FN values of the anterior third transcallosal fiber tracts were found in HFA patients compared to TD children. These results suggested that the anterior third CC density and transcallosal fiber connectivity were affected in HFA children.

Predictive models of autism spectrum disorder based on brain regional cortical thickness.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide phenotypic range, often affecting personality and communication. Previous voxel-based morphometry (VBM) studies of ASD have identified both gray- and white-matter volume changes. However, the cerebral cortex is a 2-D sheet with a highly folded and curved geometry, which VBM cannot directly measure. Surface-based morphometry (SBM) has the advantage of being able to measure cortical surface features, such as thickness. The goals of this study were twofold: to construct diagnostic models for ASD, based on regional thickness measurements extracted from SBM, and to compare these models to diagnostic models based on volumetric morphometry. Our study included 22 subjects with ASD (mean age 9.2+/-2.1 years) and 16 volunteer controls (mean age 10.0+/-1.9 years). Using SBM, we obtained regional cortical thicknesses for 66 brain structures for each subject. In addition, we obtained volumes for the same 66 structures for these subjects. To generate diagnostic models, we employed four machine-learning techniques: support vector machines (SVMs), multilayer perceptrons (MLPs), functional trees (FTs), and logistic model trees (LMTs). We found that thickness-based diagnostic models were superior to those based on regional volumes. For thickness-based classification, LMT achieved the best classification performance, with accuracy=87%, area under the receiver operating characteristic (ROC) curve (AUC)=0.93, sensitivity=95%, and specificity=75%. For volume-based classification, LMT achieved the highest accuracy, with accuracy=74%, AUC=0.77, sensitivity=77%, and specificity=69%. The thickness-based diagnostic model generated by LMT included 7 structures. Relative to controls, children with ASD had decreased cortical thickness in the left and right pars triangularis, left medial orbitofrontal gyrus, left parahippocampal gyrus, and left frontal pole, and increased cortical thickness in the left caudal anterior cingulate and left precuneus. Overall, thickness-based classification outperformed volume-based classification across a variety of classification methods.