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Introduction: Military suicide remains a significant concern in many countries. Most psychological autopsy studies in this field focused on certain psychological comorbidities with suicide, namely depression, quality of life, sporadically in different populations. However, much less attention has been paid to Attention Deficit/Hyperactivity Disorder (ADHD), which is among the most common neuropsychiatric conditions in youth. This study aimed to test the associations between childhood ADHD symptoms and several suicidal behaviors, namely suicidal ideation, self-harm behaviors, and suicidal attempts. We, then, tested whether these associations would be mediated by the level of current depression and quality of life in military recruits.Materials and Methods: A total of 1,047 military recruits (all male, aged 20-34 years) participated in this questionnaire survey. The participants completed the Swanson, Nolan, and Pelham, Version IV Scale-Chinese version for ADHD symptoms before 12 years old; the Beck Depression Inventory, 2nd edition, for depressive symptoms and quality of life for the past 6 months; the Adult ADHD Quality-of-Life Scale; and the questions about current self-harm/suicidal behaviors on the Adult Self-Report Scale Inventory-4-Chinese version. Mediation analyses with bootstrapping of total indirect effects were used for statistical analyses.Results: Our Results revealed significant associations between recalled childhood ADHD symptoms/diagnosis (age 6-12 years) and all the three current suicidal behaviors (suicidal ideation, self-harm behaviors, and suicidal attempts; all p values <0.001). Mediation analyses revealed that all these relationships were significantly and partially mediated by depression (all p values <0.05) and quality of life (p value <0.05, but not for suicidal attempts).Conclusion: The major findings of this study include that the ADHD-suicidality association is partially explained by the mediating effects of depression and quality of life, and that recalled ADHD symptoms had a stronger association with suicide attempt than with suicidal ideation in military recruits. Moreover, our finding of the highest direct effect of ADHD and lowest indirect effects of depression and quality of life on self-harm behavior indicates different associated patterns between deliberate self-harm and suicidal ideation and attempts. Our findings concord Nock's suggestion that different prevention strategies for suicidal ideation, self-harm behaviors, and suicidal attempts are warranted because of distinct courses and underlying psychopathology. This study is limited by a lack of psychiatric interview to make the diagnosis of ADHD and other psychiatric disorders, and only recruiting young men without female participants leading the generalization of our results to young women is questionable. Moreover, the lack of temporal data in this study prohibits us extend our findings to establish causality. The findings imply that assessment and intervention of depression and poor quality of life may help offset suicidal behaviors among military recruits with ADHD symptoms and/or diagnosis. Further investigations about interactions among those factors are warranted. [ABSTRACT FROM AUTHOR]

Background: We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods: We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results: We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions: We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. [ABSTRACT FROM AUTHOR]

Background: Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorders (ASD) are a group of complex childhood-onset neurodevelopmental and genetic disorders characterized by deficits in language development and verbal communication, impaired reciprocal social interaction, and the presence of repetitive behaviors or restricted interests. The study aimed to identify novel genes associated with the pathogenesis of ASD. Methods: We conducted comparative total gene expression profiling analysis of lymphoblastoid cell lines (LCL) between 16 male patients with ASD and 16 male control subjects to screen differentially expressed genes associated with ASD. We verified one of the differentially expressed genes, FOXP1, using real-time quantitative PCR (RT-qPCR) in a sample of 83 male patients and 83 male controls that included the initial 16 male patients and male controls, respectively. Results: A total of 252 differentially expressed probe sets representing 202 genes were detected between the two groups, including 89 up- and 113 downregulated genes in the ASD group. RT-qPCR verified significant elevation of the FOXP1 gene transcript of LCL in a sample of 83 male patients (10.46 ± 11.34) compared with 83 male controls (5.17 ± 8.20, P = 0.001). Conclusions: Comparative gene expression profiling analysis of LCL is useful in discovering novel genetic markers associated with ASD. Elevated gene expression of FOXP1 might contribute to the pathogenesis of ASD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between attention-deficit hyperactivity disorder (ADHD) symptoms and subtypes, and sleep schedules, daytime inadvertent napping, and sleep problems/disorders in children and adolescents with and without ADHD. The sample included 325 patients with ADHD, aged 10-17 years [male: 81.5%; combined type (ADHD-C): 174; predominantly inattentive type (ADHD-I): 130; predominantly hyperactive-impulsive type (ADHD-HI): 21], and 257 children and adolescents without lifetime ADHD (non-ADHD). We conducted psychiatric interviews with the participants and their mothers before making the diagnoses of ADHD, other psychiatric disorders, and sleep problems or disorders. We also collected the medication treatment data and parent and teacher reports of ADHD symptoms. Multi-level models were used for data analyses controlling for sex, age, psychiatric comorbidities, and treatment with methylphenidate. The ADHD-C and ADHD-I groups had more daytime inadvertent napping. In general, the three subtypes were associated with increased rates of sleep problems/disorders. Specifically, ADHD-C rather than ADHD-I was associated with circadian rhythm problems, sleep-talking, nightmares (also ADHD-HI), and ADHD-I was associated with hypersomnia. The most-related sleep schedules and problems for inattention and hyperactivity-impulsivity were earlier bedtime, later rise time, longer nocturnal sleep, more frequent daytime napping, insomnia, sleep terrors, sleep-talking, snoring, and bruxism across informants. The findings imply that in addition to the dichotomous approach of ADHD and considering the psychiatric comorbid conditions, ADHD subtypes and symptom dimensions need to be considered in clinical practice and in the research regarding the association between ADHD and sleep problems/disorders. [ABSTRACT FROM AUTHOR]

This study aimed to establish the psychometric properties of parent ratings on the Chinese version of the Swanson, Nolan, and Pelham IV scale (SNAP-IV) in a school-based sample of 3534 students in grades 1 to 8 from two cities and two suburbs in Taiwan and 189 children diagnosed with attention deficit/hyperactivity disorder (ADHD) (aged 6 to 15) consecutively recruited from a medical center in Taipei. Parents completed the Chinese versions of the SNAP-IV, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. The Chinese SNAP-IV demonstrated similar three factor structure (Inattention, Hyperactivity/Impulsivity, and Oppositional) as its English version, and satisfactory test–retest reliability (intraclass correlation = 0.59∼0.72), internal consistency (alpha = 0.88∼0.90), concurrent validity (Pearson correlations = 0.56∼0.72), and discriminant validity. Boys scored higher than girls across the eight school grade levels. The SNAP-IV clearly distinguished children with ADHD from school-based participants. Comorbidity with oppositional defiant disorder/conduct disorder predicted higher SNAP-IV scores among children with ADHD. Our findings suggest that the Chinese SNAP-IV is a reliable and valid instrument for rating ADHD-related symptoms in both clinical and community settings in Taiwan. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Although attention deficit/hyperactivity disorder (ADHD) in adulthood has become a topic of considerable interest to psychiatrists over the past decade, little is known about the prevalence or correlates of adult ADHD in the Chinese population. As a first step in addressing this problem, this study presents data on the psychometric properties of the Chinese version of the World Health Organization's Adult ADHD Self-report Scale (ASRS) in a sample of 1031 young males from an army base and 3298 young adults from two colleges. All participants completed the Chinese ASRS. Participants from an army base also completed a clinical assessment including the Wender Utah Rating Scale (WURS) for assessing childhood ADHD, the Impulsiveness Scale for measuring the severity of current impulsive behaviors, and information about substance use. Results showed good concordance (intraclass correlations = 0.80∼0.85) and internal consistency (Cronbach's alpha = 0.83∼0.91) among the ASRS subscales and moderate to high correlations between these subscales and the WURS (Pearson's correlations = 0.37∼0.66). The Chinese ASRS also demonstrated the ability to predict childhood disruptive problems and habitual use of substances. Our findings suggest that the Chinese ASRS is a reliable and valid instrument to assist in screening for adult ADHD. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to examine the association between attention-deficit-hyperactivity disorder (ADHD) and maternal psychological distress, parenting style and perceived family support, and the child's interaction with parents and behavioural problems at home in Taiwan. Methods: The sample included 375 medicated pediatric patients with DSM-IV ADHD, and 750 school controls selected based on the age and gender structures of the ADHD group. Mothers reported on the Chinese Health Questionnaire, the Chinese versions of the Parental Bonding Instrument, the Family Adaptation, Partnership, Growth, Affection, and Resolve, and the Home Behaviours of the Social Adjustment Inventory for Children and Adolescents. Results: Mothers of children with ADHD reported greater psychological distress and perceived less support from their families than did mothers of controls. Moreover, mothers of children with ADHD were less affectionate and more overprotective and controlling toward their children than were mothers of controls. This difference was more apparent in boys than in girls. Children with ADHD were less likely to interact with their parents, yet demonstrated more severe behavioural problems at home. Conclusions: Although the Taiwanese children with ADHD were under treatment with methylphenidate, they and their families still encountered a variety of difficulties in interaction, support, and communication with each other. Therefore, the parental approach should be integrated into the medication treatment for ADHD in Taiwan. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder, which has been linked to mutations or deletions of RNA binding protein, fox-1 homolog (Caenorhabditis elegans) 3 (RBFOX3)/NeuN, a neuronal splicing regulator. However, the mechanism of seizure mediation by RBFOX3 remains unknown. Here, we show that mice with deletion of Rbfox3 in gammaaminobutyric acid (GABA) ergic neurons exhibit spontaneous seizures and high premature mortality due to increased presynaptic release, postsynaptic potential, neuronal excitability, and synaptic transmission in hippocampal dentate gyrus granule cells (DGGCs). Attenuating early excitatory gamma-aminobutyric acid (GABA) action by administering bumetanide, an inhibitor of early GABA depolarization, rescued premature mortality. Rbfox3 deletion reduced hippocampal expression of vesicle-associated membrane protein 1 (VAMP1), a GABAergic neuron-specific presynaptic protein. Postnatal restoration of VAMP1 rescued premature mortality and neuronal excitability in DGGCs. Furthermore, Rbfox3 deletion in GABAergic neurons showed fewer neuropeptide Y (NPY)-expressing GABAergic neurons. In addition, deletion of Rbfox3 in NPY-expressing GABAergic neurons lowered intrinsic excitability and increased seizure susceptibility. Our results establish RBFOX3 as a critical regulator and possible treatment path for epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Despite high psychiatric comorbidities in adolescents with clinical diagnosis of attention-deficit hyperactivity disorder (ADHD), little is known about psychiatric comorbidities in their siblings. We investigated the psychiatric comorbid conditions in adolescents with ADHD, their siblings, and healthy control subjects from their school. Method: The sample included 136 adolescent probands with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-lV), diagnostic criteria; 136 siblings (47 affected and 89 unaffected) and 136 age- and sex-matched healthy school control subjects. All participants and their parents received the structured psychiatric interviews for current and lifetime DSM-IV psychiatric disorders of the participants. Results: The rate of ADHD (34.6%) in the siblings of probands with ADHD was about 7 times higher than in the general population. Probands with ADHD were significantly more likely than unaffected siblings (OR 6.38; 95% Cl 3.43 to 11.88) and healthy school control subjects (OR 9.60; 95% Cl 5.31 to 17.34) to have a DSM-IV psychiatric disorder, including oppositional defiant disorder (ODD), conduct disorder (CD), tic disorders, major depressive disorder, specific phobia (more than control subjects only), nicotine use disorder, and sleep disorders. The affected siblings were significantly more likely than healthy school control subjects to have ODD, CD, specific phobia, and to have consumed alcohol (ORs ranging from 2.30 to 20.16). Conclusions: Our findings suggest that siblings of probands with ADHD have increased risks for ADHD and that the affected siblings have more psychiatric comorbidities than healthy school control subjects. It warrants early identification of ADHD symptoms and other psychiatric comorbid conditions as well in siblings of adolescents with ADHD. [ABSTRACT FROM AUTHOR]

AbstractAttention deficit/hyperactivity disorder (ADHD) is often poorly understood, and treatment practices are variable. This 12-month, prospective, observational study provides information about the diagnosis, co-morbidities, treatment patterns, and quality of life (QOL) of patients aged 6–17 years with ADHD symptoms from eastern Asia and central and eastern Europe. Here, we present baseline data for the 1068 enrolled and eligible patients in the study (median age 8 years, 82.2% male). Patients were grouped into two cohorts based on whether they were prescribed psycho- and/or pharmacotherapy (n= 794) or not (n= 274) at study entry. On average, patients receiving treatment were significantly older (9.1 vs. 8.4 years, p< 0.001), more severely ill (Clinical Global Impressions [CGI]-ADHD-S, 4.6 vs. 4.2, p< 0.001; Child Symptom Inventory-4 Parent Checklist (CSI-4) ADHD:C, 35.2 vs. 31.9, p< 0.001), and had significantly higher CSI-4 symptom severity scores relating to various co-morbidities than patients not receiving treatment. At study initiation, patient's health-related QOL was significantly impaired as measured on the Child Health and Illness Profile–Child Edition (CHIP-CE) rating scale, with significantly more impairment in the treated group of patients for the Comfort, Risks Avoidance, and Achievement domains. These results provide a description of ADHD and treatment practices in these regions and establish a baseline for gauging changes over time in the study sample. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that cortical anatomy may be aytpical in autism spectrum disorder. The wingless-type MMTV integration site family, member 2 (WNT2), a candidate gene for autism spectrum disorder, may regulate cortical development. However, it is unclear whether WNT2 variants are associated with altered cortical thickness in autism spectrum disorder. Methods: In a sample of 118 people with autism spectrum disorder and 122 typically developing controls, we investigated cortical thickness using FreeSurfer software. We then examined the main effects of the WNT2 variants and the interactions of group × SNP and age × SNP for each hemisphere and brain region that was altered in people with autism spectrum disorder. Results: Compared to neurotypical controls, people with autism spectrum disorder showed reduced mean cortical thickness in both hemispheres and 9 cortical regions after false discovery rate correction, including the right cingulate gyrus, the orbital gyrus, the insula, the inferior frontal gyrus (orbital part and triangular part), the lateral occipitotemporal gyrus, the posterior transverse collateral sulcus, the lateral sulcus and the superior temporal sulcus. In the full sample, 2 SNPs of WNT2 (rs6950765 and rs2896218) showed age × SNP interactions for the mean cortical thickness of both hemispheres, the middle-posterior cingulate cortex and the superior temporal cortex. Limitations: We examined the genetic effect for each hemisphere and the 9 regions that were altered in autism spectrum disorder. The age effect we found in this cross-sectional study needs to be examined in longitudinal studies. Conclusion: Based on neuroimaging and genetic data, our findings suggest that WNT2 variants might be associated with altered cortical thickness in autism spectrum disorder. Whether and how these WNT2 variants might involve cortical thinning requires further investigation. [ABSTRACT FROM AUTHOR]

Background: The presence of attention-deficit/hyperactive disorder (ADHD) symptoms and impaired attention performance are commonly noted in individuals with autism spectrum disorder (ASD). However, little is known about attention performance in their unaffected siblings. This study aimed to investigate the ADHD-related traits and attention performance in unaffected siblings of probands with autism and Asperger syndrome (AS), as well as the clinical correlates of ADHD-related traits. Methods: We assessed the intention, hyperactivity-impulsivity, and oppositional symptoms, and attention profiles of 199 probands with a diagnosis of ASD (122 autism, 77 AS), their unaffected siblings, and 196 typically developing controls (TD) by their parents' reports on the ADHD-related symptoms and the Connors' Continuous Performance Test (CCPT), respectively. Results: Compared to TD, unaffected siblings of ASD probands were more hyperactive/impulsive and oppositional, particularly unaffected siblings of AS probands. In CCPT, unaffected siblings of AS have intermediate levels of performance between probands with AS and TD on focused attention and sustained attention but were not statistically different from AS probands or TD in these attention profiles. In contrast, unaffected siblings of autism probands have significantly better CCPT performance when compared to autism probands but not to TD. In addition, stereotyped behaviors predicted ADHD-related traits in both sibling groups, but distinctive patterns of other correlates for ADHD-related traits were found between the two sibling groups. Conclusions: This work suggested that unaffected siblings of AS, but not autism, have more hyperactive/impulsive traits and a trend of pervasive attention deficits assessed by CCPT which might serve as potential endophenotypes for genetic studies in AS. [ABSTRACT FROM AUTHOR]

Background: Several longitudinal studies have shown the partial symptomatic persistence of attention-deficit hyperactivity disorder (ADHD) in clinic-based samples. However, little is known about the patterns and trajectories of ADHD symptoms in community-based populations. Methods: To differentiate developmental trajectories of ADHD symptoms over 1 year, with a four-wave quarterly follow-up in children and adolescents in the community of Taiwan, we conducted this prospective study in 1281 students in grade 3, 5, and 8. All the students in the regular classes rather than special educational classes were eligible and recruited to the study. Inattention, hyperactivity-impulsivity, and opposition-defiance were rated by parent reports on the Chinese version of the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV). Group-based trajectory modeling and multivariable regression analyses were used to explore the individual, family and social factors associated with differential trajectories. Results: Trajectories were classified as Low (29.9-40.6%), Intermediate (52.5-58.5%) and High (6.9-12.5%) based on the symptom severity of ADHD symptoms assessed by the SNAP-IV. The proportion of children in the high ADHD trajectory might approximately reflect the prevalence of ADHD in Taiwan. The following factors differentiated High from Low trajectories: male gender, more externalizing problems, fewer prosocial behaviors, school dysfunction, more home behavioral problems, and less perceived family support. Conclusions: Our findings that the concurrent conditions of emotional or externalizing problems, as well as impaired school and home function at baseline, might differentiate the high ADHD symptoms trajectory from others could help developing the specific measures for managing high ADHD symptoms over time in a school setting. [ABSTRACT FROM AUTHOR]

Background: Our purpose was to examine the reliability and validity of the Chinese version of the Patient Health Questionnaire-15 (PHQ-15) in Taiwan, and to explore its relation to somatoform disorders (DSM-IV) and to somatic symptom and related disorders (DSM-5). Methods: We recruited 471 individuals, 151 with somatoform disorders and 200 with somatic symptom and related disorders. Subjects completed the Chinese version of the PHQ-15, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and received a DSM-IV- and DSM-5-based diagnostic interview. We performed exploratory factor analysis and assessed test-retest reliability, internal consistency, and correlation with BDI-II/BAI to confirm reliability and validity, and carried out ROC curve analysis to determine suitability for evaluation or screening purposes. PHQ-15 scores were compared between patients with various DSM-IV psychiatric diagnoses (such as DSM-IV somatoform disorders, panic disorder, other anxiety/depressive disorders) or no DSM-IV diagnosis and patients with DSM-5 somatic symptom and related disorders or no DSM-5 diagnosis. Results: The Chinese version identified cardiopulmonary, pain-fatigue, and gastrointestinal as major factors and had good reliability (0.803-0.930), internal consistency (0.637-0.861), and correlation coefficients with BDI-II/BAI (0.407-0.619, 0.536-0.721, respectively). The PHQ-15 scores were similar in patients with somatoform disorders and patients with panic disorder; higher in patients with somatoform disorders and panic disorder than in patients with other anxiety/ depressive disorders; and significantly higher in patients with somatic symptom and related disorders than in patients without this diagnosis. The AUC of the PHQ-15 was 0.678 (cutoff 6/7) for screening somatoform disorders (DSM-IV) and 0.725 (cutoff 4/5) for screening somatic symptom and related disorders (DSM-5). Conclusions: The Chinese version of the PHQ-15 is suitable for evaluating somatic symptom and related disorders. The preponderance of somatic symptom disorder in our sample, lack of evaluation of functional disorders, and recruitment solely from psychiatric clinics are possible limitations. [ABSTRACT FROM AUTHOR]

Background: Our purpose was to examine the reliability and validity of the Chinese version of the Patient Health Questionnaire-15 (PHQ-15) in Taiwan, and to explore its relation to somatoform disorders (DSM-IV) and to somatic symptom and related disorders (DSM-5). Methods: We recruited 471 individuals, 151 with somatoform disorders and 200 with somatic symptom and related disorders. Subjects completed the Chinese version of the PHQ-15, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and received a DSM-IV- and DSM-5-based diagnostic interview. We performed exploratory factor analysis and assessed test-retest reliability, internal consistency, and correlation with BDI-II/BAI to confirm reliability and validity, and carried out ROC curve analysis to determine suitability for evaluation or screening purposes. PHQ-15 scores were compared between patients with various DSM-IV psychiatric diagnoses (such as DSM-IV somatoform disorders, panic disorder, other anxiety/depressive disorders) or no DSM-IV diagnosis and patients with DSM-5 somatic symptom and related disorders or no DSM-5 diagnosis. Results: The Chinese version identified cardiopulmonary, pain-fatigue, and gastrointestinal as major factors and had good reliability (0.803-0.930), internal consistency (0.637-0.861), and correlation coefficients with BDI-II/BAI (0.407-0.619, 0.536-0.721, respectively). The PHQ-15 scores were similar in patients with somatoform disorders and patients with panic disorder; higher in patients with somatoform disorders and panic disorder than in patients with other anxiety/ depressive disorders; and significantly higher in patients with somatic symptom and related disorders than in patients without this diagnosis. The AUC of the PHQ-15 was 0.678 (cutoff 6/7) for screening somatoform disorders (DSM-IV) and 0.725 (cutoff 4/5) for screening somatic symptom and related disorders (DSM-5). Conclusions: The Chinese version of the PHQ-15 is suitable for evaluating somatic symptom and related disorders. The preponderance of somatic symptom disorder in our sample, lack of evaluation of functional disorders, and recruitment solely from psychiatric clinics are possible limitations. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. Methods: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). Results: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. Conclusions: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. [ABSTRACT FROM AUTHOR]

Background: Neuroanatomical differences between individuals with and without autism spectrum disorder (ASD) were inconsistent in the literature. Such heterogeneity may substantially originate from age-differential effects. Methods: Voxel-based morphometry was applied in 86 males with ASD and 90 typically developing control (TDC) males (aged 7 to 29 years). Three steps of statistical modeling (model 1, multiple regression with age as a covariate; model 2, multiple regression further considering diagnosis-by-age interaction; model 3, age-stratified analyses) were performed to dissect the moderating effects of age on diagnostic group differences in neuroanatomy. Results: Across ages, males with and without ASD did not differ significantly in total gray matter (GM) or white matter (WM) volumes. For both groups, total GM volumes decreased and WM volumes increased with age. For regional volume, comparing with the model only held the age constant (model 1), the main effect of group altered when diagnosis-byage interaction effects were considered (model 2). Here, participants with ASD had significantly greater relative regional GM volumes than TDC in the right inferior orbitofrontal cortex and bilateral thalamus; for WM, participants with ASD were larger than TDC in the bilateral splenium of corpus callosum and right anterior corona radiata. Importantly, significant diagnosis-by-age interactions were identified at the bilateral anterior prefrontal cortex, bilateral cuneus, bilateral caudate, and the left cerebellum Crus I for GM and left forceps minor for WM. Finally, age-stratified analyses (model 3) showed distinct patterns in GM and WM volumetric alterations in ASD among subsamples of children, adolescents, and adults. Conclusions: Our findings suggest that the heterogeneous reports on the atypical neuroanatomy of ASD may substantially originate from age variation in the study samples. Age variation and its methodological and biological implications have to be carefully delineated in future studies of the neurobiology of ASD. [ABSTRACT FROM AUTHOR]

This study examined the effects and mediators of a clinic-based intervention program (CBIP) and a home-based intervention program (HBIP) compared with usual care in very-low-birth-weight (VLBW) preterm infants on developmental and behavioral outcomes at 24 months of age (corrected for prematurity). In this randomized controlled trial, VLBW preterm infants received either CBIP (n=57), HBIP (n=63), or usual care (n=58) from hospitalization to 12 months. At 12 months, infant emotional regulation was assessed using the toy-behind-barrier procedure and dyadic interaction was observed during free play. At 24 months, infant developmental and behavioral outcomes were assessed using the Bayley Scales of Infant and Toddler Development- 3rd edition and the Child Behavior Checklist for Ages 1.5-5, respectively. Compared with infants under usual care, the CBIP-group infants showed higher cognitive composite scores (difference, 95% confidence interval (CI)=4.4, 0.8-7.9) and a lower rate of motor delay (odds ratio (OR), 95% CI=0.29, 0.08-0.99); the HBIP-group infants had lower sleep problem scores (difference, 95% CI=-1.4, -2.5 to -0.3) and a lower rate of internalizing problems at 24 months (OR, 95% CI=0.51, 0.28-0.93) (all p<.05). The CBIP's effect on cognitive outcome was attenuated when maternal or dyadic interactive behavior was considered; whereas the HBIP's effect on sleep and internalizing behavior was attenuated when duration of orientation to a toy or object was considered. In conclusions, interventions enhanced the cognitive, motor, and behavioral outcomes of VLBW preterm infants. The effects on cognitive and behavioral outcomes might be mediated by early-improved mother-infant interaction and infant emotional regulation, respectively. [ABSTRACT FROM AUTHOR]

Background GABRB3 is a position candidate gene at chromosome 15q12 that has been implicated in the neurobiology of autism spectrum disorders (ASD). The aim of this study was to examine the genetic association of GABRB3 with ASD. Methods The sample consisted of 356 patients with clinical diagnosis of ASD according to the DSMIV diagnostic criteria and confirmed by the Autism Diagnostic Interview-Revised and 386 unrelated controls. We searched for mutations at all the exonic regions and 1.6 Kb of the 5' region of GABRB3 in the genomic DNA of all the participants using the Sanger sequencing. We implemented a case-control association analysis of variants detected in this sample, and conducted a reporter gene assay to assess the functional impact of variants at the 5' regulatory region. Results We detected six known common SNPs; however, they were not associated with ASD. Besides, a total of 22 rare variants (12 at 5' regulatory, 4 at intronic, and 6 at exonic regions) were detected in 18 patients and 6 controls. The frequency of rare variants was significantly higher in the patient group than in the control group (18/356 versus 6/386, odds ratio = 3.37, P = 0.007). All the 12 rare variants at the 5' regulatory region were only detected in 7 patients, but not in any of the controls (7/356 versus 0/386, Fisher's exact test, P = 0.006). Two patients carried multiple rare variants. Family studies showed that most of these rare variants were transmitted from their parents. Reporter gene assays revealed that four rare variants at the 5' regulatory region and 1 at exon 1a untranslated region had elevated reporter gene activities compared to two wild type alleles. Conclusions Our data suggest rare variants of GABRB3 might be associated with ASD, and increased GABRB3 expression may contribute to the pathogenesis of ASD in some patients. Trial registration Clinical trial registration: Identifier: NCT00494754 [ABSTRACT FROM AUTHOR]

Objective: The authors sought to assess the risk of cerebrovàscular events associated with use of antidepressant medications. Method: The authors conducted a casecrossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows. Results: The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1 37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants. Conclusions: These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear. [ABSTRACT FROM AUTHOR]