Kevin M. Antshel

Symptoms versus Impairment: The Case for Respecting "DSM-IV"'s Criterion D.

Diagnosing ADHD based primarily on symptom reports assumes that the number/frequency of symptoms is tied closely to the impairment imposed on an individual’s functioning. That presumed linkage encourages diagnosis more by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) style symptom lists than well-defined, psychometrically sound assessments of impairment. The current study correlated measures reflecting each construct in four separate, large-scale ADHD research samples. Average correlation between symptoms and impairment accounted for less than 10% of variance. Symptoms never predicted more than 25% of the variance in impairment. When an ADHD group was formed according to a measure of current symptoms, the sample size shrunk by 77% when a criterion-based measure of impairment was added. The partial unlinking of symptoms and impairment has implications for decisions about the diagnostic process, research criteria for participant inclusion, prevalence estimates, gender ratios, evaluation of treatment effects, service delivery, and many other issues.

Phenylalanine hydroxylase deficiency: Diagnosis and management guideline

Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder. Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120–360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine hydroxylase deficiency is in early stages with one approved medication (sapropterin, a derivative of the natural cofactor of phenylalanine hydroxylase) and others under development. Eventually, treatment of phenylalanine hydroxylase deficiency will be individualized with multiple medications and alternative medical foods available to tailor therapy. The primary goal of therapy should be to lower blood phenylalanine, and any interventions, including medications, or combination of therapies that help to achieve that goal in an individual, without other negative consequences, should be considered appropriate therapy. Significant evidence gaps remain in our understanding of the optimum therapies for phenylalanine hydroxylase deficiency, nonphenylalanine effects of these therapies, and long-term sequelae of even well-treated disease in children and adults.Genet Med 16 2, 188–200.

Velo-cardio-facial syndrome

Purpose of review Velo-cardio-facial syndrome has emerged from obscurity to become one of the most researched disorders this past decade. It is one of the most common genetic syndromes in humans, the most common contiguous gene syndrome in humans, the most common syndrome of cleft palate, and the most common syndrome of conotruncal heart malformations. Velo-cardio-facial syndrome has an expansive phenotype, a factor reflected in the wide range of studies that cover both clinical features and molecular genetics. In this review, we cover multiple areas of research during the past year, including psychiatric disorders, neuroimaging, and the delineation of clinical features. Recent findings The identification of candidate genes for heart anomalies, mental illness, and other clinical phenotypes has been reported in the past year with a focus on TBX1 for cardiac and craniofacial phenotypes and COMT and PRODH for psychiatric disorders. The expansive phenotype of velo-cardio-facial syndrome continues to grow with new behavioral and structural anomalies reported. Treatment issues are beginning to draw attention, although most authors continue to focus on diagnostic issues. Summary Its high population prevalence, estimated to be as common as 1:2000 has sparked a large amount of research, as has the model the syndrome serves for identifying the causes of mental illness and learning disabilities, but it is obvious that more information is needed. Intensive scrutiny of velo-cardio-facial syndrome will undoubtedly continue for many years to come with the hope that researchers will turn more of their attention to treatment and treatment outcomes.

Social Skills Training in Children With Attention Deficit Hyperactivity Disorder: A Randomized-Controlled Clinical Trial

Evaluated efficacy of social skills training (SST) on children with 2 subtypes of attention deficit hyperactivity disorder (ADHD). Participants were 120 children (30 girls, 90 boys), ages 8 to 12 with ADHD-Inattentive type (ADHD-I; n = 59) or Combined type (ADHD-C; n = 61). The children were randomly assigned within diagnosis subtype to the treatment condition (8 weeks of SST) or the no-intervention control condition. SST led to greater improvements in both parent- and child-perceived assertion skills in the children with ADHD, yet did not affect the other domains of social competence. Diagnostically heterogeneous groups led to greater improvements on parent-report of their childs cooperation and assertion abilities as well as childrens report of their own empathy skills. Diagnostically homogeneous groups led to greater decreases in externalizing behaviors at posttreatment but not at follow-up. Children with comorbid oppositional defiant disorder (ODD) did not benefit as much from the intervention. Children with ADHD-I improved in assertion skills more than children with ADHD-C, yet the 2 diagnostic entities did not differ in improvement levels across all other social skills.

Integrating culture as a means of improving treatment adherence in the Latino population

Treatment adherence is a significant challenge within the field of paediatrics. Culture is an important clinical variable to consider in treatment and adherence to medical regimens. Consideration of common elements of the Latino culture is a viable mechanism to improving treatment adherence. These shared elements include language, familismo, respeto, personalismo, espiritism, simpatia, fatalismo , and a crisis orientation. In addition, acculturation is presented as it pertains to treatment adherence. Each cultural variable is discussed as a means of improving treatment adherence and the importance of culturally competent care is forwarded. The importance of theory-driven research and future research directions are discussed.

Advances in understanding and treating ADHD

Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability.

Psychosocial Interventions in Attention Deficit Hyperactivity Disorder

This brief overview of psychosocial treatment approaches to attention deficit hyperactivity disorder (ADHD) concentrates on the two that receive the greatest research support, parent training in child behavior management and teacher training in classroom management. Cognitive-behavioral training of children who have ADHD has little evidence of efficacy and group social skills training has mixed or limited evidence of effectiveness. Research should focus on more theoretically driven psychosocial treatment approaches, on potential side effects or adverse events associated with this form of intervention, and on the complex pathways that affect impairment in major life activities that could guide subsequent treatment design for such impairments.

A gender-moderated effect of a functional COMT polymorphism on prefrontal brain morphology and function in velo-cardio-facial syndrome (22q11.2 deletion syndrome)

Caused by a microdeletion at the q11.2 locus of chromosome 22, velo‐cardio‐facial syndrome (also known as VCFS, 22q11 deletion syndrome, DiGeorge sequence, and conotruncal anomalies face syndrome) is associated with a distinctive physical, neurocognitive, and psychiatric phenotype. Increasing interest has centered on identifying the candidate genes within the deleted region that may contribute to this phenotype. One attractive candidate gene is catechol‐O‐methyltransferase (COMT) because it encodes for a protein that degrades dopamine. Variability in COMT activity is related to a Val158Met polymorphism that has been implicated in prefrontal lobe cognitive and neuropsychiatric function. We examined the effect of this polymorphism on prefrontal anatomy and frontally‐mediated neuropsychological function in 58 children with VCFS, 26 who were hemizygous for the Met allele and 32 for the Val allele. We found an allele by gender interaction effect on the volumes of the dorsal prefrontal and orbital prefrontal cortices. We did not find significant allele or gender by allele effects on neuropsychological tasks, although girls with the Met allele tended to perform better on the Wisconsin card sorting task. These data suggest that this functional COMT polymorphism may play a gender‐moderated role in determining the neuroanatomic phenotype of individuals with VCFS. Longitudinal evaluation of these children is essential in order to identify potential clinical implications of this allele by gender interaction.

Cognitive Decline Preceding the Onset of Psychosis in Patients With 22q11.2 Deletion Syndrome

IMPORTANCE Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age. OBJECTIVE To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS. DESIGN, SETTING, AND PARTICIPANTS Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with ≥1 assessment at age 8-24 years). MAIN OUTCOMES AND MEASURES Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test. RESULTS Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95% CI, 1.24-5.00; P = .01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward. CONCLUSIONS AND RELEVANCE In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.

Comorbid ADHD and anxiety affect social skills group intervention treatment efficacy in children with autism spectrum disorders.

Objective: To assess the influence of psychiatric comorbidity on social skill treatment outcomes for children with autism spectrum disorders (ASDs). Methods: A community sample of 83 children (74 males, 9 females) with an ASD (mean age = 9.5 yr; SD = 1.2) and common comorbid disorders participated in 10-week social skills training groups. The first 5 weeks of the group focused on conversation skills and the second 5 weeks focused on social problem solving skills. A concurrent parent group was also included in the treatment. Social skills were assessed using the Social Skills Rating System. Ratings were completed by parents at pre- and posttreatment time periods. Results: Children with ASD and children with an ASD and comorbid anxiety disorder improved in their parent reported social skills. Children with ASD and comorbid attention deficit/hyperactivity disorder failed to improve. Conclusion: Psychiatric comorbidity affects social skill treatment gains in the ASD population.