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Obsessive-compulsive disorder (OCD) is a heritable childhood-onset psychiatric disorder that may represent the extreme of obsessive-compulsive (OC) traits that are widespread in the general population. We report the heritability of the Toronto Obsessive-Compulsive Scale (TOCS), a new measure designed to assess the complete range of OC traits in youth. We also examined the dimensional nature of the TOCS and the degree to which genetic effects are unique or shared between dimensions. OC traits were measured using the TOCS in 16,718 youth (6-18 years) at a science museum. We conducted a factor analysis to identify OC trait dimensions. We used univariate and multivariate twin models to estimate the heritability of OC trait dimensions in a subset of twins (220 pairs). Six OC dimensions were identified: Cleaning/Contamination, Symmetry/Ordering, Rumination, Superstition, Counting/Checking, and Hoarding. The TOCS total score (74%) and each OC dimension was heritable (30-77%). Hoarding was not highly correlated with other OC dimensions, but did share genetic effects. Shared genetics accounted for most of the shared variance among dimensions, whereas unique environment accounted for the majority of dimension-specific variance. One exception was Hoarding, which had considerable unique genetic factors. A latent trait did not account for the shared variance between dimensions. In conclusion, OC traits and individual OC dimensions were heritable, although the degree of shared and dimension-specific etiological factors varied by dimension. The TOCS may be informative for genetic research of OC traits in youth. Genetic research of OC traits should consider both OC dimension and total trait scores.

Objective: Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest early morning functional (EMF) impairments before school. We conducted a quantitative research survey to assess the impact of these EMF impairments on the family unit (caregiver, spouse/partner, and siblings)., Study Design: We developed an online survey questionnaire to collect data from 300 primary caregivers of children with ADHD and 50 primary caregivers of children who did not have ADHD., Results: Although the ADHD children we surveyed were currently treated with stable doses of stimulants as their primary ADHD medication for at least 3 months, their parents reported high levels of EMF impairments in the child, which had a substantial negative effect on the emotional well-being of parents, on parents' functioning during the early morning routine, and on the level of conflict with siblings. The impact of EMF impairments on family functioning was mediated by the severity of the index child's impairments., Conclusions: EMF impairments exert a pervasive and significantly negative emotional and functional burden on not only the primary caregiver but also on the spouse/partner and siblings. This work suggests that adequate ADHD symptom control during the early morning period may be an unmet need for school-age children with ADHD being treated with stimulants. More work is needed to confirm this finding and determine the degree to which symptom control at other times of day is also an unmet need.

Oxytocin is a pituitary neuropeptide that affects social behaviour. Single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) have been shown to explain some variability in social abilities in control populations. Whether these variants similarly contribute to the severity of social deficits experienced by children with neurodevelopmental disorders is unclear. Social abilities were assessed in a group of children with autism spectrum disorder (ASD, n = 341) or attention deficit hyperactivity disorder (ADHD, n = 276) using two established social measures. Scores were compared by OXTR genotype (rs53576, rs237887, rs13316193, rs2254298). Unexpectedly, the two most frequently studied OXTR SNPs in the general population (rs53576 and rs2254298) were associated with an increased severity of social deficits in ASD (p < 0.0001 and p = 0.0005), yet fewer social deficits in ADHD (p = 0.007 and p < 0.0001). We conclude that these genetic modifier alleles are not inherently risk-conferring with respect to their impact on social abilities; molecular investigations are greatly needed.

Introduction: Survival rates for children with acute lymphoblastic leukemia (ALL) approach 95%. At the same time, there is growing concern that chemotherapy causes alterations in brain development and cognitive abilities. We performed MRI measurements of white and gray matter volume to explore how variation in brain structure may be related to cognitive abilities in ALL survivors and healthy controls., Methods: The sample included 24 male ALL survivors who had completed contemporary treatment 3-11 years prior, and 21 age- and sex-matched controls. Participants were between 8 and 18 years old. Working memory and motor response inhibition were measured with the N-Back and Stop Signal Tasks (SST), respectively. Participants underwent 3T structural MRI to assess white and gray matter volumes overall, lobe-wise, and in cortical and atlas-identified subcortical structures. Mental health was assessed with the Child Behavioral Checklist., Results: ALL survivors performed more poorly on measures of working memory and response inhibition than controls. Frontal and parietal white matter, temporal and occipital gray matter volume, and volumes of subcortical white and gray matter structures were significantly reduced in ALL survivors compared with controls. Significant structure-function correlations were observed between working memory performance and volume of the amygdala, thalamus, striatum, and corpus callosum. Response inhibition was correlated with frontal white matter volume. No differences were found in psychopathology., Conclusions: Compared with controls, a reduction in volume across brain regions and tissue types, was detectable in ALL survivors years after completion of therapy. These structural alterations were correlated with neurocognitive performance, particularly in working memory. Confirming these observations in a larger, more representative sample of the population is necessary. Additionally, establishing the time course of these changes-and the treatment, genetic, and environmental factors that influence them-may provide opportunities to identify at-risk patients, inform the design of treatment modifications, and minimize adverse cognitive outcomes.

Objective: To describe the Toronto Obsessive-Compulsive Scale (TOCS), a novel 21-item parent- or self-report questionnaire that covers wide variation in obsessive-compulsive (OC) traits, and to evaluate its psychometric properties in a community-based pediatric sample., Method: The TOCS was completed for 16,718 children and adolescents between the ages of 6 and 17 years in a community setting. Internal consistency, convergent validity with the Obsessive-Compulsive Scale of the Child Behaviour Checklist (CBCL-OCS), divergent validity with the Strengths and Weaknesses of ADHD (Attention-Deficit/Hyperactivity Disorder) Symptoms and Normal Behaviour Rating Scale (SWAN), interrater reliability, as well as sensitivity and specificity of the TOCS were assessed., Results: The internal consistency of the 21 TOCS items was excellent (Cronbach's α = 0.94). TOCS was moderately correlated with the CBCL-OCS (Spearman correlation = 0.51) and poorly correlated with the SWAN (Pearson correlation = 0.02). Sensitivity and specificity analyses indicated that a TOCS total score of greater than 0 successfully discriminated community-reported obsessive-compulsive disorder (OCD) cases from noncases. OC traits were continuously distributed both at the total score and dimensional level in our pediatric community sample., Conclusion: TOCS is a multidimensional measure of OC traits in children and adolescents with sound psychometric properties. TOCS reveals that OC traits are common and continuously distributed in a community sample. TOCS may be a useful measure for studies of the characteristics and etiology of OC traits., (Copyright © 2016. Published by Elsevier Inc.)

Objective: Traumatic brain injury (TBI) is the most common cause of death and disability in children and adolescents. Psychopathology is an established risk factor for, and a frequent consequence of, TBI. This paper reviews the literature relating psychopathology and TBI., Method: Selective literature review., Results: The risk of sustaining a TBI is increased by pre-existing psychopathology (particularly ADHD and aggression) and psychosocial adversity. Even among individuals with no psychopathology prior to the injury, TBI is frequently followed by mental illness especially ADHD, personality change, conduct disorder and, less frequently, by post-traumatic stress and anxiety disorders. The outcome of TBI can be partially predicted by pre-injury adjustment and injury severity, but less well by age at injury. Few individuals receive treatment for mental illness following TBI., Conclusion: TBI has substantial relevance to mental health professionals and their clinical practice. Available evidence, while limited, indicates that the risk for TBI in children and adolescents is increased in the presence of several, potentially treatable mental health conditions and that the outcome of TBI involves a range of mental health problems, many of which are treatable. Prevention and management efforts targeting psychiatric risks and outcomes are an urgent priority. Child and adolescent mental health professionals can play a critical role in the prevention and treatment of TBI through advocacy, education, policy development and clinical practice.

Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

Objective: Several neurodevelopmental disorders are associated with social processing deficits. The objective of this study was to compare patterns of social perception abilities across obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and control participants., Method: A total of 265 children completed the Reading the Mind in the Eyes Test-Child Version (RMET). Parents or caregivers completed established trait/symptom scales. The predicted percentage of accuracy on the RMET was compared across disorders and by item difficulty and item valence (i.e., positive/negative/neutral mental states), then analyzed for associations with trait/symptom scores., Results: The percentage of correct RMET scores varied significantly between diagnostic groups (p < .0001). On pairwise group comparisons controlling for age and sex, children with ADHD and ASD scored lower than the other groups (p < .0001). When IQ was also controlled for in the model, participants with OCD performed better than controls (p < .001), although differences between other groups were less pronounced. Participants with ASD scored lowest on easy items. Those with ASD and ADHD scored significantly lower than other groups on items with positive valence (p < .01). Greater social communication impairment and hyperactivity/impulsivity, but not OCD traits/symptoms, were associated with lower scores on the RMET, irrespective of diagnosis., Conclusion: Social perception abilities in neurodevelopmental disorders exist along a continuum. Children with ASD have the greatest deficits, whereas children with OCD may be hypersensitive to social information. Social communication deficits and hyperactive/impulsive traits are associated with impaired social perception abilities; these findings highlight overlapping cognitive and behavioral manifestations across disorders., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.

The objective of this prospective longitudinal study was to assess the nature, rate, predictive variables, and neuroimaging characteristics of novel (new-onset) anxiety disorders (compared with no novel anxiety disorders) 6-12 months after pediatric traumatic brain injury (TBI). Psychiatric and psychosocial interviews were administered to children who sustained mild to severe TBI at baseline (soon after injury) and at the 12-month follow-up post-injury (n= 125). The psychiatric outcome of children 12-months post-injury revealed that novel anxiety disorders present in the second six months after TBI were heterogeneous and occurred in 13 (10.4%) participants. Novel anxiety disorder was significantly associated with concurrent novel depressive disorder and with novel personality change due to TBI. Novel anxiety disorder was marginally associated with younger age at injury and with pre-injury anxiety disorder in univariate analyses. Age at injury, pre-injury anxiety disorder, and personality change due to TBI were each significantly and independently related to novel anxiety disorder in a logistic regression analysis. There were no significant neuroimaging group differences. These findings suggest that the emergence of novel anxiety disorder after TBI might be related to a broader problem of affective dysregulation especially in younger children and those with a vulnerability even to pre-injury anxiety disorder.

The present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6-16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions., Competing Interests: The other authors have no disclosures.

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

The objective of this study was to understand how novel psychiatric disorders (NPD) in children with mild traumatic brain injury (MTBI) are related to pre-injury variables, injury-related variables, and concurrent neurocognitive outcome. A group of 79 children, ages 5 to 14 years, who had experienced MTBI, were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline); 60 children were reassessed 12 months post-injury. Standardized instruments were used to assess injury severity; lesion characteristics; pre-injury variables, including psychiatric disorder, family psychiatric history, family functioning, socioeconomic status, psychosocial adversity, adaptive functioning, and post-injury neurocognitive and adaptive functioning. NPD occurred in 17 of 60 participants (28%) in the 6-12-month interval after injury, with disorders that were significantly associated with socioeconomic status, psychosocial adversity, estimated pre-injury academic functioning, and concurrent deficits in adaptive functioning, academic performance, processing speed, memory, and expressive language. NPD was not significantly associated with pre-injury adaptive functioning, injury severity, family psychiatric history, pre-injury psychiatric disorder, lesion location, gender, or age at injury. These findings suggest that the short-term psychiatric morbidity associated with MTBI in children occurs more commonly than previously reported and is related to both pre-injury social factors and concurrent neurocognitive functioning.

The objective was to assess the nature, rate, predictive factors, and neurocognitive correlates of novel psychiatric disorders (NPD) after mild traumatic brain injury (MTBI). Children age 5-14 years with MTBI (N=87) from consecutive admissions to five trauma centers were enrolled and studied with semistructured psychiatric interviews soon after injury (baseline), and 70 of these children were assessed again 6 months post-injury. Injury severity; lesion characteristics; pre-injury variables, including psychiatric disorder, family psychiatric history, family functioning, socioeconomic status, psychosocial adversity, and adaptive functioning; and post-injury neurocognitive and adaptive functioning measures were assessed with standardized instruments. NPD occurred in 25 of 70 participants (36%) in the first 6 months after injury. NPD at 6 months was predicted by the presence of frontal white-matter lesions on MRI at 3 months post-injury, and was associated with concurrent decrements on neurocognitive indices of processing speed, expressive language, and intellectual functioning. NPD was not predicted by other indices of severity, pre-injury psychosocial variables, estimated pre-injury academic functioning, or adaptive and executive function decrements 6 months post-injury. These findings suggest that short-term psychiatric morbidity associated with MTBI in children and adolescents may be more common than previously thought and may have readily identifiable neuroimaging and neurocognitive correlates.

Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general population, heritable and shared genetic risk with ADHD traits. Participants were 16,099 children and adolescents, ages 6 to 18 years who visited a local science center. We measured ADHD traits using the Strengths and Weaknesses of ADHD-symptoms and Normal-Behavior (SWAN) rating scale and performance on the stop signal task (SST)-response inhibition (SSRT), response latency (GoRT), and response variability (GoRTSD). Regression analysis was used to assess the relationship of cognitive measures and ADHD traits while controlling for family, age, sex, ethnicity, socioeconomic status and treatment status. Heritability of ADHD and cognitive traits was estimated using SOLAR in 7,483 siblings from 3,507 families that included multiple siblings. Bivariate relationships between pairs of variables were examined. Individuals with greater ADHD trait scores had worse response inhibition, slower response latency, and greater variability. Younger participants and girls had inferior performance although the gender effects were minimal and evident in youngest participants. Inhibition, latency, variability, total ADHD traits, inattention and hyperactivity-impulsivity scores were significantly heritable. ADHD traits and inhibition, but not latency or variability were coheritable. In the largest study in the general population, we found support for the validity of response inhibition as an endophenotype of ADHD.

The objective was to assess the nature, rate, predictive factors, and neuroimaging correlates of novel (new-onset) depressive disorders, both definite and subclinical, after traumatic brain injury (TBI). Children with TBI from consecutive admissions were enrolled and studied with psychiatric interviews soon after injury (baseline), and again 6 months post-injury. Novel definite/subclinical depressive disorders at 6-month follow up occurred in 11% (n=15) of the children and subsets of children with non-anxious depression (n=9) and anxious depression (n=6) were identified. Novel definite/subclinical depressive disorder was significantly associated with older age at the time of injury, family history of anxiety disorder, left inferior frontal gyrus (IFG) lesions, and right frontal white matter lesions. Non-anxious depressions were associated with older age at injury, left IFG and left temporal pole lesions. Anxious depressions were associated with family history of anxiety disorder, Personality Change due to TBI, right frontal white matter lesions, and left parietal lesions. These findings, which are similar to those reported after adult TBI, identify both similarities and differences in non-anxious and anxious depression following childhood TBI with respect to lesion laterality, genetic factors (in the form of family psychiatric history of anxiety disorder), age at injury, and more generalized affective dysregulation., (Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.)

The study's objective was to assess the nature, rate, predictive factors, and neuroimaging correlates of novel (new-onset) definite anxiety disorders and novel definite/subclinical anxiety disorders (in a broader group of children with at least subclinical anxiety disorders) after traumatic brain injury (TBI). Children with TBI from consecutive admissions to five trauma centers were enrolled and studied with psychiatric interviews soon after injury (baseline) and again 6 months post-injury. Novel definite anxiety disorder and novel definite/subclinical anxiety disorders were heterogeneous and occurred in 8.5% (N=12) and 17% (N=24) of participants, respectively, in the first 6 months after injury. Novel definite anxiety disorder was significantly associated with younger age at injury and tended to be associated with novel depressive disorder, as well as lesions of the superior frontal gyrus. Novel definite/subclinical anxiety disorder was significantly associated with concurrent psychiatric problems of personality change due to TBI and novel definite/subclinical depressive disorder, as well as with lesions of the superior frontal gyrus and a trend-association with frontal lobe white-matter lesions. These findings suggest that anxiety after childhood TBI may be part of a broader problem of affective dysregulation related to damaged dorsal frontal lobe and frontal white-matter systems, with younger children being at greatest risk for developing novel anxiety disorder after TBI.

Objective: The purpose of the present study was to develop reliable and valid parent and teacher scales for measurement of functional impairment in children and adolescents in order to assist the diagnosis of attention-deficit/hyperactivity disorder (ADHD)., Methods: Seventy-two children with ADHD fulfilling the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition criteria and forty-two normal controls were enrolled in this study. Parents and teachers of the subjects completed the parent and teacher form of the preliminary items of Child and Adolescent Functioning Impairment Scale (CAFIS) made up by the authors. Based on the reliability and factor analysis, the final parent (CAFIS-parent form) and teacher version (CAFIS-teacher form) were constructed. Scales were analyzed for reliability and validity. Relative operating characteristics curve was drawn to calculate the cutoff scores of these scales for children with ADHD., Results: The CAFIS-parent and CAFIS-teacher forms consist of four and three factors, respectively. Internal consistency and test-retest correlation of the scales were satisfactory. The CAFIS and Children's Global Assessment Scale were significantly correlated. All scores of subscales of CAFIS in ADHD group were significantly higher than those of control group. The sensitivity and specificity of the subscales were mostly at an appropriate level., Conclusion: The CAFIS is a brief layperson-administered scale to assess functional impairment of children and adolescents. It can be a useful tool for parents and teachers to objectively measure the functions of children at home and in school. This scale was found to be reliable and valid, and it appears to be a valuable instrument in Korean language.

We report the heritability of response inhibition, latency, and variability, which are potential markers of genetic risk in neuropsychiatric conditions. Genetic and environmental influences on cancellation and restraint, response latency, and variability measured in a novel variant of the stop signal task were studied in 139 eight-year-old twin pairs from a birth cohort. Cancellation (50%), restraint (27%), and response latency (41%) showed significant heritability, the balance being non-shared environmental influences and/or error. Response variability was not heritable, with 23% of the variance attributable to shared environmental influences and 77% to non-shared environmental risk or error. The phenotypic correlation between response cancellation and restraint was -.44 and between response latency and restraint was .21. These phenotypic correlations were entirely genetic in origin. The phenotypic correlation between response variability and % successful inhibition was .27, but was not genetic. Cancellation and restraint were heritable and shared genetic influences, indicating that they may be influenced by a common gene or genes. Response latency was moderately heritable and shared genetic influences with restraint, but was not correlated with cancellation. Response variability was not heritable. These results support the potential of response inhibition and latency as endophenotypes in genetic research.

Previous error detection research has focused on error processing functions in the anterior cingulate cortex or on putative reinforcement learning roles of midbrain dopamine pathways. We studied error detection in 14 healthy adult volunteers using a novel fMRI design in the stop signal task (SST), a task which invokes numerous errors in performance and frequent instances of post-error slowing. The imaging design accommodated variability immediately before errors (handedness of response) and immediately after (degree of post-error slowing) using distinct within-trial regressors. This approach revealed a whole-brain view of error detection in a reinforcement-learning pathway. Error detection deactivated the midbrain in the vicinity of dorsal substantia nigra where dopamine neurons originate, and the primary targets of dopamine neurons: dorsal striatum and ventral anterior cingulate. Error detection also deactivated posterior hippocampus, which is highly sensitive to long-term synaptic plasticity effects of dopamine. Errors that led to slowed responses deactivated structures in the reciprocal pathway that are known to exert control over dopamine output, and which have been shown to encode error magnitude: ventral midbrain, ventral striatum, and caudal orbitofrontal cortex. Consistent with the role of these structures in modulating dopamine output, post-error slowing also increased activities in the same structures that deactivated on error detection. These results are consistent with the view that errors deactivate structures that receive input from dopamine neurons, followed by deactivations related to requisite behavioral adjustments in structures that exert control over dopamine output., (Copyright 2010 Elsevier Inc. All rights reserved.)

Autism is a common neurodevelopmental disorder with a complex mode of inheritance. It is one of the most highly heritable of the complex disorders, although the underlying genetic factors remain largely unknown. Here, we report mutations in the X-chromosome PTCHD1 (patched-related) gene in seven families with autism spectrum disorder (ASD) and in three families with intellectual disability. A 167-kilobase microdeletion spanning exon 1 was found in two brothers, one with ASD and the other with a learning disability and ASD features; a 90-kilobase microdeletion spanning the entire gene was found in three males with intellectual disability in a second family. In 900 probands with ASD and 208 male probands with intellectual disability, we identified seven different missense changes (in eight male probands) that were inherited from unaffected mothers and not found in controls. Two of the ASD individuals with missense changes also carried a de novo deletion at another ASD susceptibility locus (DPYD and DPP6), suggesting complex genetic contributions. In additional males with ASD, we identified deletions in the 5' flanking region of PTCHD1 that disrupted a complex noncoding RNA and potential regulatory elements; equivalent changes were not found in male control individuals. Thus, our systematic screen of PTCHD1 and its 5' flanking regions suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.

Linkage of attention deficit hyperactivity disorder (ADHD) to the short arm-centromeric region of chromosome 5 has been reported in multiple studies. The overlapping region (5p13-q11) contains a number of strong candidate genes for ADHD, based on their role in brain function or neurodevelopment. The aim of this study was to investigate some of the top candidates among these genes in relation to ADHD in a sample of 245 nuclear families from the Toronto area. We investigated the genes for the glial cell-derived neurotropic factor (GDNF), the fibroblast growth factor 10 (FGF10), islet-1 (ISL1), the hyperpolarized potassium channel (HCN1) and the integrin alpha 1 (ITGA1). In addition to these genes, we assessed the 3'region of the SLC1A3 gene, a glutamate transporter implicated in ADHD by a previous association study. A total of 36 polymorphisms were selected across the six genes. We performed family-based association and haplotype analyses. ADHD is a dimensional disorder, with symptoms of inattention and hyperactivity-impulsivity therefore, we also conducted quantitative analysis in relation to symptom scores for both dimensions. Single marker and haplotype analyses yielded little evidence of association for any of the genes tested in this study. Moreover, we were unable to replicate the positive association findings reported for SLC1A3. Our results suggest that these six genes are unlikely to be susceptibility genes in the chromosome 5p13-q11 region and other genes should now be considered for priority study., (Copyright 2007 Wiley-Liss, Inc.)

ADHD is a heritable condition of childhood for which several risk alleles have been identified. However, observed effect sizes have been small and few replicated polymorphisms have been identified. There are many reasons for the lack of one-to-one correspondence between genotype and phenotype in ADHD. Endophenotypes are non-clinical markers of genetic risk which may facilitate gene discovery in complex disorders like ADHD. The most common endophenotypes under consideration in ADHD are neuropsychological measures of executive function, although a range of psychological, physiological and neuroanatomical endophenotypes have been proposed. If carefully chosen, endophenotypes have the potential to increase the power of genetic research to identify susceptibility genes. If not carefully selected, endophenotypes may generate false negative and false positive results. This paper reviews the theoretical rationale for endophenotypes and proposes a priori criteria by which ADHD endophenotypes should be selected and validated. The literature on motor response inhibition is reviewed to illustrate the validation process which is recommended in the selection of other candidate endophenotypes.

Background: The goal of this study was to compare the predictive validity of the two main diagnostic schemata for childhood hyperactivity - attention-deficit hyperactivity disorder (ADHD; Diagnostic and Statistical Manual- IV) and hyperkinetic disorder (HKD; International Classification of Diseases- 10th Edition)., Methods: Diagnostic criteria for ADHD and HKD were used to classify 419 children ages 6 to 16 years referred to a clinic for behavioral problems into one of four groups: HKD, ADHD combined subtype (ADHD-C), ADHD hyperactive-impulsive subtype (ADHD-HI), ADHD inattentive subtype (ADHD-IA). These groups were compared on clinical characteristics including total symptom severity, overall impairment, exposure to psychosocial and neuro-developmental risks, family history of ADHD in first-degree family members, rate and type of comorbidity, intelligence, academic achievement, and on laboratory tests of motor response inhibition and working memory with each other and with normal controls (47)., Results: Of the 419 cases, there were 46 HKD (11.0%), 200 ADHD-C (47.7%), 60 ADHD-HI (14.3%) and 113 ADHD-IA (27.0%) cases. The HKD group had more symptoms and was more impaired on teachers' ratings than were the other groups. The ADHD-C and HKD groups had poorer inhibitory control than the ADHD-IA, ADHD-HI and control groups, and all four clinic groups showed inhibition deficit compared to controls. Groups did not differ in working memory. Compared to controls, the HKD, ADHD-C, ADHD-HI and ADHD-IA groups had higher familial risk of ADHD, greater psychosocial risk exposure, lower intellectual level and poorer academic attainment. However, we observed no differences among the clinic groups in these characteristics., Conclusions: Like earlier versions, ICD-10 and DSM-IV continue to delineate diagnostic entities with substantially different prevalence in clinic samples. However, HKD, ADHD-C, ADHD-IA and ADHD-HI groups overlap substantially in terms of important clinical characteristics, although HKD and ADHD-C may be somewhat more severe variants of the condition than ADHD-IA and ADHD-HI.

Anxiety disorder (ANX) is characterized by heightened arousal, psychosocial and academic difficulties, and comorbidity with other disorders, in particular, attention-deficit/hyperactivity disorder (ADHD). The heightened arousal contributes to cognitive impairment by adversely affecting executive control of cognition. The nature of the effect on executive control is poorly understood. Research in this area could inform intervention, diagnostic, and etiological research. Our objective was to characterize children with ANX on measures of executive functioning, while controlling for comorbid ADHD. We compared children ages 6-14 with ANX (N=21), ADHD (N=78), ANX+ADHD (N=38), and normal controls (NC; N=40) on the stop task, a measure of performance monitoring and response inhibition. No difference was observed between NC and ANX groups in performance monitoring. Compared to the NC group, the three clinical groups showed inhibition deficits, and both ADHD and ANX+ADHD groups monitored less after responses. ANX was not associated with performance monitoring or inhibition deficits once comorbid ADHD was considered. This emphasizes the importance of controlling for comorbid ADHD in studies of cognition and anxiety.

Phenomenology and predictive factors of personality change due to traumatic brain injury (TBI) 6 to 24 months after injury was investigated in children, ages 5 to 14 years, enrolled from consecutive admissions and followed prospectively for 2 years. Injury and preinjury psychosocial variables were assessed. Personality change occurred in 13% of participants between 6 and 12 months after injury and 12% in the second year after injury. Severity of injury consistently predicted personality change, and preinjury adaptive function predicted personality change only in the second year postinjury. Lesions of the superior frontal gyrus were associated with personality change between 6 and 12 months following injury, after controlling for severity of injury and the presence of other brain lesions. Only lesions in the frontal lobe white matter were significantly related to personality change in the second year after injury. After childhood TBI, neural correlates of personality change evolve between 6 and 12 months and 12 to 24 months after injury. The data implicate the dorsal prefrontal cortex and frontal lobe white matter in the emergence of personality change involving the effortful or conscious regulation of affective states.

Objective: To describe the properties of a semistructured research interview of parents designed to evaluate attention-deficit hyperactivity disorder (ADHD) and related psychopathology., Method: We examined interrater reliability in 48 videotaped interviews randomly selected from a large clinic sample. We examined convergence of the Parent Interview for Child Symptoms (PICS) and Conners' Parent Rating Scale (CPRS) scores in 594 clinic-referred cases and 26 control subjects, comparing the groups generated by cross-tabulation on measures of intelligence, academic achievement, and inhibitory control., Results: Intraclass correlation coefficients for symptom scores of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) were excellent. We found good reliability for diagnoses of ADHD (e = 0.73) and CD (kappa = 0.73) and excellent reliability for the diagnosis of ODD (kappa = 0.80). Two-thirds of cases were classified similarly on the PICS and the CPRS. Greater impairment in inhibitory control was observed in cases identified as ADHD by the PICS, compared with those identified by the CPRS-ADHD index., Conclusions: The PICS displays good reliability and validity, indicating that a balance between clinical applicability and reliability can be achieved in the development of clinical research instruments.

Objective: To assess the phenomenology and predictive factors of attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (SADHD)., Method: Children without preinjury ADHD 5-14 years old with TBI from consecutive admissions (n = 143) to five trauma centers were observed prospectively from 6 to 12 months (12-month assessment) and from 12 to 24 months (24-month assessment) postinjury with semistructured psychiatric interviews. Injury and preinjury psychosocial variables were assessed., Results: SADHD occurred in 15 of 103 (15%) of participants between 6 and 12 months after injury and 17 of 82 (21%) in the second year after injury. SADHD was significantly (p < .05) comorbid with personality change due to TBI and new-onset disruptive behavior disorders. Preinjury adaptive function was a consistent predictor of SADHD. Regression analyses revealed that preinjury psychosocial adversity was an independent predictor of SADHD in the second year after injury. Neither severity of injury nor lesion location predicted SADHD from 6 to 24 months postinjury., Conclusions: Determination of preinjury psychosocial adversity and the child's preinjury functioning during the index hospitalization would improve identification of children at highest risk of development of SADHD.

Objective: To assess the phenomenology and predictive factors of attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (SADHD)., Method: Children without preinjury ADHD 5-14 years old with TBI from consecutive admissions (n = 143) to five trauma centers were observed prospectively for 6 months (baseline and 6 months), with semistructured psychiatric interviews. Injury severity, lesion characteristics, and preinjury variables including psychiatric disorder, family psychiatric history, family psychiatric history of ADHD, family function, socioeconomic status, psychosocial adversity, and adaptive function were assessed with standardized instruments., Results: SADHD in the first 6 months after injury occurred in 18 of 115 (16%) of returning participants. All subtypes of ADHD occurred. Socioeconomic status (p = .041) and orbitofrontal gyrus lesions (p = .005) independently significantly predicted SADHD., Conclusions: These findings are consistent with research on developmental ADHD that implicate psychosocial factors and prefrontal structural and functional differences between those with and without the disorder.

Objective: The authors sought to determine whether nonaffected siblings of ADHD probands have a motor response inhibition deficit and to assess concordance for this inhibition deficit in ADHD-concordant and ADHD-discordant sibling pairs., Method: ADHD-concordant pairs (21 probands and their affected siblings), ADHD-discordant pairs (18 probands and their nonaffected siblings), and a group of unrelated, demographically balanced, healthy individuals (N=24) were compared on measures of response inhibition, ADHD behavior, impairment, and environmental risk., Results: Concordant-pair probands, their affected siblings, and discordant-pair probands exhibited inhibitory control impairment relative to healthy comparison subjects. The performance of nonaffected siblings was intermediate between that of ADHD children and the healthy comparison subjects. Group differences persisted after age was controlled, and performance was not correlated with the number of ADHD symptoms. In ADHD-concordant sibling pairs, there was a significant relationship between proband and sibling inhibition deficit. In ADHD-discordant sibling pairs, inhibition deficit was evident in half of the nonaffected siblings of probands with an inhibition deficit. Groups did not differ in exposure to environmental risks., Conclusions: Impaired inhibitory control aggregates in the family members of individuals with ADHD and may serve as an indicator of genetic vulnerability to the disorder.

We studied error monitoring in ADHD and control children in a task requiring inhibition of a motor response. The extent of slowing following successful (stopped) and failed (nonstopped) inhibition was compared across groups. We also measured the time required to inhibit a response (stop signal reaction time, SSRT). Compared to controls, ADHD participants slowed less following nonstopped responses. Slowing did not vary with comorbid reading, oppositional, conduct or anxiety disorder, sex or ADHD subtype. Slowing after nonstopped responses was marginally, although significantly correlated with total ADHD symptoms and with age. ADHD participants had significantly longer SSRT than controls, but SSRT was not significantly correlated with slowing. The apparent deficit in error monitoring in ADHD and its independence from the inhibition deficit observed in ADHD has implications for executive control models of ADHD, performance problems associated with the disorder and for component theories of executive control.

Objective: To identify approaches to improving methods for assessing tolerability and safety of psychotropic medications in children and adolescents., Method: Strengths and limitations of current methodology were reviewed and possible alternatives examined., Results: Research on the validity of safety evaluation has been extremely limited. No evidence-based "gold standard" exists. Clinical trials remain the best design to establish causality, but sample size limitations prevent the detection of infrequent, though serious, adverse events. Other designs, such as cohort and case-control studies, and approaches, such as mining of large databases, must be considered., Conclusion: The current lack of methodological standardization across studies prevents generalizations and meta-analyses. Because the issues relevant to drug safety are diverse, a variety of methodological approaches and instruments are needed. It is, however, possible to adopt standard basic definitions of adverse events, degree of severity, ascertainment methods, and recording procedures, as a common "core," to which more specific assessment instruments can be added. Systematic empirical testing and validation of safety methodology is needed.

Objective: To identify moderators and mediators of long-term adherence to stimulant medication in children with attention-deficit hyperactivity disorder (ADHD)., Method: Seventy-one children with ADHD were prescribed methylphenidate, followed prospectively on an annual basis for 3 years, and evaluated for adherence to stimulant treatment. The study occurred in Toronto between 1993 and 1997. Adherents were those who took methylphenidate, or another psychostimulant, for 5 or more days per week throughout the follow-up period, except for "drug holidays." Children who adhered at consecutive evaluations were compared with those who did not. Severity of ADHD, presence of oppositional defiant disorder/conduct disorder, learning difficulties, anxiety, age, family dysfunction, and socioeconomic adversity at baseline were investigated as moderators of adherence. Response to treatment at school, measured at 12 months, was investigated as a mediator of adherence., Results: Fifty-two percent of children adhered to stimulant treatment for 3 years. Absence of teacher-rated oppositional defiant disorder, more teacher-rated ADHD symptoms, and younger age at baseline predicted adherence., Conclusions: Adherence to stimulant medications is a significant factor in the long-term treatment of children with ADHD.

Objective: There is considerable evidence supporting a genetic component in the etiology of attention-deficit/hyperactivity disorder (ADHD). Because stimulant medications act primarily on the dopaminergic system, dopamine system genes are prime candidates for genetic susceptibility factors for ADHD. Previous studies by several groups have observed a significant association of ADHD and an allele with 7 copies of the 48 base pair repeat in the third exon of the dopamine D4 receptor., Method: The authors sought to replicate these previous findings by collecting an independent sample of families from Toronto, Ontario, Canada, and confirming this finding in an expanded sample of ADHD families collected from Irvine, California. Using the transmission disequilibrium test (TDT), the authors tested for biased transmission of the 7-repeat allele at the exon III polymorphism of the dopamine D4 receptor locus in these samples of ADHD subjects., Results: Biased transmission of the 7-repeat allele from parents to ADHD probands and their affected siblings was observed in the 2 new samples of families collected in Toronto and Irvine (TDT chi2 = 2.711, 1 df, one-sided p value = .050) and for these samples combined with the 52 families previously reported from Irvine (TDT chi2 = 6.426, 1 df, one-sided p value = .006)., Conclusions: The results of this study further support the possibility of a role of the dopamine D4 receptor locus in ADHD.

Objective: The current diagnostic algorithm for attention-deficit/hyperactivity disorder (ADHD) is not highly predictive of impairment and yields low interrater agreement. The objective of this study was to enhance the diagnostic accuracy of ADHD by identifying the symptoms that are associated with impairment., Method: Semistructured interviews and impairment rating scales were administered to parents and teachers of 218 children. Combinations of ADHD symptoms were examined according to a receiver operating characteristic (ROC) based procedure to create diagnostic algorithms that predict impairment., Results: In comparison with the DSM-IV, the ROC-based algorithms were 2 to 3 times more efficient in discriminating impaired from nonimpaired children. Parent and teacher agreement was also 3 times higher., Conclusions: Limiting the diagnosis to symptoms that predict impairment can increase the validity of the ADHD diagnosis. Results also support the use of ROC analyses in developing better diagnostic algorithms.

Objective: To study nonverbal social cue perception in children with attention-deficit/hyperactivity disorder (ADHD; n = 86), conduct problems (CP; n = 24), or both disorders (ADHD + CP; n = 63), as well as normal controls (n = 27)., Method: Using a standardized test of receptive nonverbal processing abilities, participants were required to interpret emotional cues from pictures of facial expressions and recordings of voices., Results: As predicted, children with CP and ADHD were significantly less accurate at interpreting emotions than normal controls. However, children with CP and ADHD differed in the type of errors made: the ADHD group's errors were generally random in nature, whereas the CP group tended to misinterpret emotions as anger. Contrary to our hypothesis, the ADHD + CP group performed better than the ADHD and CP groups, was as accurate as the control group, and displayed a unique pattern of errors., Conclusions: These results support the idea that social deficiencies associated with CP arise from a biased perception of emotion, whereas social problems in ADHD originate from a failure to attend to the appropriate cues of affect. The findings also support the theory that comorbid ADHD + CP is a distinct disorder.

Objective: To compare subtypes of attention-deficit/hyperactivity disorder (ADHD) (predominantly inattentive and combined types) and a comparison group on an objective measure of activity level (actigraphy)., Method: Actigraphs were worn by 64 children (49 boys, 15 girls) during a full-day clinical diagnostic assessment; 20 subjects had a diagnosis of ADHD predominantly inattentive type, 22 had ADHD combined type, and 22 were non-ADHD controls. Mean actigraph scores were calculated for two 2-hour intervals, comprising, respectively, a psychometric evaluation in the morning and the completion of a speech and language assessment and research measures in the afternoon., Results: There were no significant group differences in activity level in the morning session. During the afternoon session, children with ADHD were significantly more active than controls, but there were no differences between ADHD subtypes., Conclusions: These data partially support specifications in the DSM-IV regarding hyperactivity in ADHD; however, they also indicate that situational and/or temporal factors may affect the degree to which hyperactivity is expressed. Furthermore, the findings contradict specifications in the DSM-IV that suggest that children with ADHD combined type should be more hyperactive than children with ADHD predominantly inattentive type.

Objective: To determine whether typical clinical doses of methylphenidate (MPH) cause tics or exacerbate preexisting mild to moderate tics., Method: Ninety-one children with attention-deficit hyperactivity disorder, with and without comorbid tics (excluding severe tics and Tourette's syndrome), were randomly assigned to receive MPH or a placebo in a 1-year prospective study. The target dose was titrated to balance behavior change and side effects. Parents and teachers were the observers., Results: Crossover from the placebo to MPH was common because of poor behavioral response. One MPH-treated subject dropped out; the final MPH group had 72 subjects; the placebo group, 18. The average dose of MPH was 0.5 mg/kg twice daily. Clinically significant tics developed in 19.6% of the subjects without preexisting tics receiving MPH and in 16.7% of those receiving the placebo (Fisher exact test, p = .59, not significant; relative risk = 1.17, confidence interval = 0.31-4.40). Deterioration of tics was observed in 33% of subjects with preexisting tics receiving MPH and in 33% of those receiving the placebo (Fisher exact test, p = .70, not significant; relative risk = 1.0, confidence interval = 0.40-1.85)., Conclusions: Doses of MPH based on the typical clinical titration procedure did not produce significantly more tics than the placebo in children with or without preexisting (mild to moderate) tics.

Objective: To determine whether comorbid anxiety alters response to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder (ADHD)., Method: Ninety-one children with ADHD were assessed for anxiety. Children were randomly assigned to receive MPH or placebo, titrated to a dose of 0.7 mg/kg, while side effects were minimized. Measures of side effects and behavioral response were obtained from parents and teachers before treatment, after titration to optimal dose, and after 4 months of treatment. These measures, dose of drug, and rate of adherence to assigned medication assignment were compared for nonanxious (ADHD- ANX) and anxious ADHD children (ADHD+ ANX)., Results: Rates of adherence to original medication assignment did not differ between the groups. ADHD+ ANX on both MPH and placebo titrated to a lower dose at the end of titration, although the dose of drug did not differ among the groups after 4 months of treatment. No differential response to MPH between ADHD+ ANX and ADHD- ANX was noted at end-titration or at 4 months on any side effect or behavioral measures., Conclusions: Comorbid anxiety does not appear to influence development of side effects or behavioral response to MPH when dose is titrated as in standard clinical practice.

The stop-signal procedure was used to examine the development of inhibitory control. A group of 275 participants, 6 to 81 years of age, performed a visual choice reaction time (go) task and attempted to inhibit their responses to the go task when they heard a stop signal. Reaction times to the stop and go signals were used to assess performance in inhibition and response execution, respectively. Results indicated the speed of stopping becomes faster with increasing age throughout childhood, with limited evidence of slowing across adulthood. By contrast, strong evidence was obtained for age-related speeding of go-signal reaction time throughout childhood, followed by marked slowing throughout adulthood. Hierarchical regression confirmed that the age-related change in inhibitory control could not be explained by general speeding or slowing of responses. Findings are discussed in regard to the contrast between the development of inhibition and response execution and the utility of the stop-signal procedure.

Objective: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD)., Method: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects., Results: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers., Conclusions: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.

A story retelling task was used to assess narrative abilities in 30 boys with attention deficit hyperactivity disorder (ADHD) and 30 normally developing boys, matched on age and IQ. Each boy listened to two stories and retold them for another child. Results indicated that the two groups did not differ in their ability to comprehend and extract the main ideas from the stories, but did differ in the production of narratives. Boys with ADHD provided less information overall, and their stories were more poorly organized and less cohesive and contained more inaccuracies. As a result, their stories were often confused and hard to follow. Organization and monitoring of information are functions of executive control. Thus the observed deficits in narrative production in children with ADHD may reflect underlying deficits in executive processes.

This study investigated the effects of methylphenidate (MPH) on inhibitory control in hyperactive children. A double-blind, placebo-control, within-subject (crossover) design was used in which 12 children, between 6 and 11 years of age, were each tested four times in each drug condition: 0.3 mg/kg and 1.0 mg/kg of methylphenidate, and placebo. Dependent measures included (a) the probability of inhibiting responses to a primary choice reaction time task given a stop signal, on the Stopping Task, and (b) response latency and errors on the Matching Familiar Figures Test (MFFT). MPH improved the efficiency of the central inhibitory mechanism by speeding the inhibitory process, thereby affording the children greater control over their actions and enabling them to increase the probability with which they inhibited responses given a stop signal. MPH increased response latency but did not reduce errors on the MFFT, and observation of the children's task performance highlighted the interpretive problems associated with this task. Performance on both tasks was better at a dosage of 1.0 mg/kg than at 0.3 mg/kg.

The attitudes of child psychiatry residents toward the use of psychotropic medication in child psychiatric practice were studied. Eighteen residents underwent a semistructured interview that covered their experience in child psychiatry, beliefs about etiology of child psychopathology, preferences for treatment, attitude toward and experience with drugs in treating childhood disturbances. The residents favored a psychosocial view of the etiology of child disturbance and preferred family therapy to other forms of treatment. Six had never treated a child with medication and most were uncertain about indications for drug use and felt they had less than average or poor skills in this area. Seven residents, who did not attend department psychopharmacology seminars and had little clinical experience with drugs, had a strong antipathy toward their use. Experience with and attitude toward drug use could not be predicted from the residents' appraisal of their own competence in this field, their experience in child psychiatry, their appreciation of the biological contributions to child psychopathology, or their future practice plans.

In the present study, the effects of 0.3 mg/kg and 1.0 mg/kg of methylphenidate on the overt behavior and academic functioning of 12 children with an established diagnosis of attention deficit disorder with hyperactivity were evaluated. A double-blind, placebo-control, within-subject (crossover) design was used, in which each child was tested four times in each drug condition. Drug conditions were alternated on a bidaily basis and each child received two different drug conditions each day. The academic tasks were designed for evaluation of the relationship between task complexity and dose. Whereas overt behavior improved with increasing dose, academic functioning was improved with methylphenidate, but did not vary with either dose or task complexity. Also, investigated were potential carryover effects of a morning dose of methylphenidate on performance in the afternoon. Behavioral and academic improvements produced by a dose of 0.3 mg/kg in the morning were no longer evident in the afternoon, but a morning dose of 1.0 mg/kg produced behavioral improvements that were clinically and statistically discernible in the afternoon, although the academic improvements had dissipated.