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Author(s): Gagan Joshi [sup.1] [sup.2] [sup.3] , Janet Wozniak [sup.1] [sup.2] [sup.3] , Maura Fitzgerald [sup.1] [sup.2] , Stephen Faraone [sup.4] [sup.5] , Ronna Fried [sup.1] [sup.2] [sup.3] , Maribel [...], To assess prevalence and severity of emotional dysregulation (ED) in psychiatrically referred youth with autism spectrum disorder (ASD). ASD youth (N = 123) were compared to youth with attention-deficit/hyperactivity disorder (ADHD) and controls. The majority of psychiatrically referred youth with ASD had positive Child Behavior Checklist-ED (CBCL-ED) profile that was significantly higher than in youth with ADHD (82 vs. 53%; p < 0.001). The severe emotional dysregulation (SED) profile was significantly greater in ASD youth than ADHD (44 vs. 15%; p < 0.001). In the presence of SED profile ASD youth suffered from greater severity of autism, associated psychopathology, and psychosocial dysfunction. Greater than expected prevalence of SED in psychiatrically referred youth with ASD that identifies distinct clinical correlates associated with severe morbidity and dysfunction.

Introduction Many individuals with attention-deficit/hyperactivity disorder (ADHD) have impaired response inhibition (i.e., a compromised ability to suppress inappropriate responses). (1) Functional neuroimaging studies of response inhibition have typically implicated 2 [...], Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. Results: We found no significant gene x environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Limitations: Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. Conclusion: While we found no evidence of gene x environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

Author(s): Qi Chen 1,*, Yanli Zhang-James 2, Eric J. Barnett 3,4, Paul Lichtenstein 1, Jussi Jokinen 5,6, Brian M. D'Onofrio 1,7, Stephen V. Faraone 2,3, Henrik Larsson 1,8, Seena Fazel [...], Background Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the Swedish national registry data for prediction of suicidal behavior. Methods and findings The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval [CI] = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown. Conclusions By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation.

Introduction Autism spectrum disorder (ASD) refers to a developmental disorder characterized by impairments in socialization and communication in the presence of restricted, repetitive behaviors and is estimated to affect up [...], To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (pervasive developmental disorder not otherwise specified). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction. Keywords Autism spectrum disorder * Psychiatric comorbidity * Youth

Advances in the field of child psychiatric genetics since the drafting of the human genome are described. Research on the genetics of developmental psychopathology has grown exponentially during this period.

The use of the quantitative trait locus approach identifies the genetic basis for autism spectrum disorder symptoms in children with attention-deficit/hyperactivity disorder. The findings support the hypothesis that differential genetic factors causes the three autistic spectrum disorder.

A novel family-based association tests (FBATs) is developed for ascertained samples that integrates unselected, genotyped controls from a population-based study into an over-all statistical test. The performance of the approach is demonstrated by an application to a genome-wide association studies (GWAS) of attention deficit hyperactivity disorder parent-offspring trios and publicly available controls.

The links of chromosomes 1p21, 6p21, and 8q21 to the Child Behavior Checklist Juvenile Bipolar Disorder (CBCL-JBD) are examined. Findings indicate an increased probability that genes in these regions affect variation on the CBCL-JBD and emotional and behavioral dysregulation associated with psychopathology.

The prediction of prodromal psychosis in adolescents with velocardiofacial syndrome is investigated. The best predictors of adolescent prodromal psychotic symptoms are parent ratings of childhood odd/eccentric symptoms and performance on the Wisconsin Card Sorting Test.

The growth of children who were treated with lisdexamfetamine dimesylate (LDX) for attention deficit hyperactivity disorder was compared with norms from the Centers for Disease Control and it is found that there are growth delays in this group in terms of weight and body mass index. The growth of children being treated with LDX should be monitored and growth delays should be corrected.

A meta-analysis of 16 subjective and objective sleep studies with a sample of 722 children with attention deficit hyperactivity disorder (ADHD) versus a control that numbers 638 shows that the children with ADHD are significantly more impaired in most of the subjective and some of the objective sleep measures than their counterpart.

Four hundred forty-four subjects aged 6-55 years were evaluated to examine the role of COMT and SLC6A4 genes in the risk for conduct disorder and its symptomatic subtypes in the context of attention deficit hyperactivity disorder. No significant association is found between these genes and the risk for conduct disorder.

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness. psychopathology | working memory | fMRI | functional connectivity | genetic risk

Analysis of the data from a genetics study of children with Attention-deficit/hyperactivity disorder (ADHD) and their affected or unaffected siblings finds that ADHD-affected children had significantly more motor problems than their unaffected siblings. It is concluded that there is a common basis between ADHD and motor problems that may be due to genetic factors.

The article reviews existing literature on the effects of stimulant medications on the growth of children with attention-deficit/hyperactivity disorder. It concludes that treatment with stimulants in childhood results in moderate growth deficit in height and weight.

Genome-wide linkage analyses are performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study. During the study it is observed that endophenotypes approaches increase the power to detect susceptibility loci in ADHD and in other complex disorders.

A study was conducted to establish the relationship between Attention-Deficit/Hyperactivity (ADHD) disorder and high-IQ children and whether ADHD has a high predictive value among youths with high-IQ. Results further supported the hypothesis for the predictive validity of ADHD in high-IQ youths.

The association between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD) in adolescent and young adult females is evaluated. Findings indicate that MD emerging in the context of ADHD is an impairing and severe comorbidity which needs to be considered further clinically and scientifically.

Ongoing debate over the validity of the attention-deficit/hyperactivity disorder (ADHD) construct in adulthood is fueled in part by uncertainty regarding implications of potentially extensive yet incompletely described comorbid Axis I and II psychopathology. Three hundred sixty-three adults ages 18 to 37 completed semistructured clinical interviews; informants were also interviewed, and best estimate diagnoses were obtained. Results were as follows: First, ADHD combined type (ADHD-C) had an excess of externalizing and internalizing Axis I disorders, suggesting a gradient-of-severity relationship between it and ADHD inattentive type (ADHD--I). Second, ADHD--C and ADHD--I did not differ in frequency of Axis II disorders. Third, however, ADHD overall was associated with increased rates of Axis II disorders, compared with rates in non-ADHD control participants, including both Cluster B (primarily borderline personality disorder) and Cluster C disorders. Fourth, ADHD incrementally accounted for clinician-rated global assessment of functioning scores above and beyond comorbid conditions or symptoms on either Axis I or Axis II. Results further inform nosology of ADHD in adults. Keywords: attention-deficit/hyperactivity disorder (ADHD), comorbidity, DSM-IV subtypes, personality disorders, functional impairment

This study examined neuropsychological deficits among children with bipolar disorder while attending to its comorbidity with attention-deficit/hyperactivity disorder (ADHD). Seventy-three unmedicated children (ages 6-17 years) with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) bipolar disorder plus ADHD (BPD + ADHD) were compared with 102 unmedicated children with ADHD without bipolar disorder, and 120 children without bipolar disorder or ADHD. Ninety-four percent of participants were Caucasian, 58% were male, and 42% were female. On average participants were of middle to upper socioeconomic status. Participants were assessed with a comprehensive neuropsychological battery and measures of academic achievement, school failure, and special education placement. Participants with BPD + ADHD and with ADHD were impaired in interference control, verbal learning, and arithmetic achievement and had higher rates of special school services. Across all of the measures of neuropsychological functioning, the only difference observed between youths with BPD + ADHD and youths with ADHD was that youths with BPD + ADHD performed more poorly on one measure of processing speed. Thus, comorbidity with ADHD may account for many of the neuropsychological deficits observed in children with bipolar disorder. Keywords: neuropsychology, bipolar disorder, child, ADHD, processing speed

The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder that persists in a sizable number of adults who had been diagnosed as having ADHD in childhood. Many adults with ADHD experience co-occurring disorders and have impaired success in academic achievement, career development, automobile driving, and interpersonal relationships. Emerging treatment strategies include structured psychotherapies, stimulant, and nonstimulant medications.

Objective. The validity of parent reports of children&apos;s attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned, especially in clinical trials. Some advocate the exclusive use of teacher reports, maintaining that parent reports are not sensitive to changes in ADHD symptoms. This study compares the ability of parent and teacher reports to document change during clinical trials of long-acting treatments. Methods. We conducted a literature search of Medline to identify any published clinical trials in pediatric ADHD that met the following criteria: 1) used a randomized design, 2) examined the efficacy of long-acting agents or standard formulations using 3-times-a-day dosing, and 3) used both parent and teacher reports of the same measure of ADHD symptoms as a study outcome. For each measurement of ADHD symptoms, we calculated effect sizes for parent and teacher reports. Results. Three large, randomized, controlled clinical trials were identified (N = 1445 subjects). For every outcome for which teacher reports documented significant improvement, parent reports did also. Pooled analysis revealed a larger effect captured by the parent report relative to the teacher report. Conclusion. Results suggest that parent reports are at least as sensitive to detecting change in ADHD symptoms as teacher reports in clinical trials that assess the efficacy of long-acting agents. These results suggest that parent reports are informative for detecting change during treatment of children with ADHD. Pediatrics 2004; 113:1667-1671; ADHD, clinical trials, pooled analysis, long-acting treatments, parent reports., ABBREVIATIONS. ADHD, attention-deficit/hyperactivity disorder; MTA, Multimodal Treatment of ADHD; tid, 3 times a day; IR, immediate-release; MPH, methylphenidate; OROS, ostomotic-release oral system; SNAP, Swanson, Nolan, and Pelham questionnaire. Clinical trials [...]

The role of genetic and environmental influences on age of initiation of first sexual relations and engaging in sexual activity with multiple partners (10 or more partners in 1 year) was investigated in male twins (N D 6; 744) from the Vietnam Era Twin Registry. Individual differences in both types of sexual behaviors were heritable, but only age of onset of sexual relations was significantly influenced by the environment shared by the twins. There was a moderate negative correlation between age of initiation of sexual relations and the multiple partners variable; initiating sexual relations earlier was associated with a higher probability of having multiple partners. The additive genetic influence on age of initiation also influenced the multiple partners variable. The substantial unique environmental influences on each variable were uncorrelated with each other. The data suggest that the observed association between age of initiation of sexual relations and having multiple partners is due to genetic influences common to both behaviors. KEY WORDS: sexual behavior; multiple sexual partners; twins; genetics.

The role of genetic and environmental influences on age of initiation of first sexual relations and engaging in sexual activity with multiple partners (10 or more partners in 1 year) was investigated in male twins (N = 6, 744) from the Vietnam Era Twin Registry. Individual differences in both types of sexual behaviors were heritable, but only age of onset of sexual relations was significantly influenced by the environment shared by the twins. There was a moderate negative correlation between age of initiation of sexual relations and the multiple partners variable; initiating sexual relations earlier was associated with a higher probability of having multiple partners. The additive genetic influence on age of initiation also influenced the multiple partners variable. The substantial unique environmental influences on each variable were uncorrelated with each other. The data suggest that the observed association between age of initiation of sexual relations and having multiple partners is due to genetic influences common to both behaviors. KEY WORDS: sexual behavior; multiple sexual partners; twins; genetics.

Objective. Although the relationship between putative growth deficits and attention-deficit/hyperactivity disorder (ADHD) has been examined in boys, this issue has not been evaluated in girls. Methods. Height and weight were examined in 124 female ADHD children and 116 female controls using age and parental height corrections, attending to issues of pubertal stage and treatment. Also, we examined the interaction between ADHD status and gender on growth outcomes using data from 124 ADHD and 109 control males. Results. The ADHD-growth association was not moderated by gender. No deficits in age-adjusted height or age and height-adjusted weight were detected in ADHD girls. Also, we found no association between growth measurements and psychotropic treatment, malnutrition, short stature, pubertal development, family history of ADHD, or psychiatric comorbidity, except for major depression: ADHD girls with major depression were on average 7.6 kg heavier than ADHD girls without depression, adjusting for age and height. Conclusions. No growth deficits appear to be associated with ADHD or its treatment in females. These findings add to a growing literature supporting the notion that stimulant treatment does not have an adverse impact on ADHD children&apos;s growth and development. Pediatrics 2003;111:1010-1016; ADHD, growth, stimulants., ABBREVIATIONS. ADHD, attention-deficit/hyperactivity disorder; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; MD, major depression; SES, socioeconomic status. Although an early literature from the 1970s suggested that [...]

Within families, co-occurring attention-deficit/hyperactivity disorder (ADHD) in parents and children may be common. The authors evaluated the hypothesis that parental ADHD may lead to a reporting bias of ADHD symptoms in offspring. They combined 2 family case-controlled studies of ADHD using structured interviews. They compared rates of maternal reported ADHD symptoms among 3 groups of ADHD children: no parental ADHD (n = 231), mother with ADHD (n = 63), and father with ADHD (n = 57). With the exception of 1 symptom, the rates of reporting between groups did not differ. There was no evidence that the discrepancy between maternal reports and self-reports of symptoms differed by parental ADHD. Results were similar across child gender or referral status. These results do not support the notion that parental ADHD affects maternal reports of offspring ADHD.

Objective. Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. Methods. A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. Results. Six studies--2 with follow-up in adolescence and 4 in young adulthood--were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. Conclusion. Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders. Pediatrics 2003;111:179-185; attention-deficit/hyperactivity disorder, substance use, pharmacotherapy., Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder that is presented for treatment. It is estimated to affect from 4% to 9% of youths. (1-3) Pharmacotherapy in general and [...]

Tobacco use is significantly associated with schizophrenia. However, it is not clear if smoking is associated with the illness itself, treatment, or underlying vulnerability to the disease. Smoking was studied in a sample of schizophrenic probands (n = 24), their unaffected co-twins (n = 24), and controls (n = 3,347). Unaffected co-twins had higher rates of daily smoking than controls. Probands and co-twins were more frequently unsuccessful in attempts to quit than controls. Probands reported shaky hands and depression following smoking cessation more often than controls, whereas unaffected co-twins reported difficulty concentrating, drowsiness, nervousness, and headache following smoking cessation more often than controls. Results are consistent with the hypothesis that nicotine use is influenced by familial vulnerability to schizophrenia, not just clinical schizophrenia per se.