John Pomeroy

Comparison of DSM-IV symptoms in elementary school-age children with PDD versus clinic and community samples

This study compares DSM-IV symptoms in children (ages 6 to 12 years) with pervasive developmental disorder (PDD), clinic controls, and community-based samples. Parents/teachers completed the Child Symptom Inventory–4 for four samples: PDD (N= 284/284) and non-PDD psychiatric clinic referrals (N= 189/181) and pupils in regular (N= 385/404) and special (N= 61/60) education classes. The PDD group received higher symptom severity ratings than the regular education group, but was similar to the non-PDD clinic sample. Screening prevalence rates were highest for ADHD, ODD, and generalized anxiety disorder. PDD subtypes exhibited differentially higher rates of psychiatric symptoms. The magnitude of rater and gender differences in symptom severity ratings was modest. Clinic-referred children with PDD exhibit a pattern of psychiatric symptoms highly similar to nonPDD clinic referrals. Although much additional research is needed on comorbidity, these symptoms have important treatment implications.

Disruption of contactin 4 in three subjects with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a developmental disorder of the central nervous system of largely unknown aetiology. The prevalence of the syndrome underscores the need for biological markers and a clearer understanding of pathogenesis. For these reasons, a genetic study of idiopathic ASD was undertaken. Methods and results: Array based comparative genomic hybridisation identified a paternally inherited chromosome 3 copy number variation (CNV) in three subjects: a deletion in two siblings and a duplication in a third, unrelated individual. These variations were fluorescence in situ hybridisation (FISH) validated and the end points further delineated using a custom fine tiling oligonucleotide array. Polymerase chain reaction (PCR) products unique to the rearrangements were amplified and sequence analysis revealed the variations to have resulted from Alu Y mediated unequal recombinations interrupting contactin 4 (CNTN4). Conclusion: CNTN4 plays an essential role in the formation, maintenance, and plasticity of neuronal networks. Disruption of this gene is known to cause developmental delay and mental retardation. This report suggests that mutations affecting CNTN4 function may be relevant to ASD pathogenesis.

Autism and epilepsy: Cause, consequence, comorbidity, or coincidence?

Autism is associated with epilepsy in early childhood, with evidence suggesting that individuals with both autism and more severe cognitive impairment are at higher risk. However, the incidence of an abnormal electroencephalogram and/or epilepsy in the full range of pervasive developmental disorders (PDDs) is not well defined. This naturalistic study addresses the incidence of epilepsy and electroencephalographic abnormalities in children with PDDs. The clinical history and electroencephalograms of 56 children diagnosed with PDD-not otherwise specified, autism, or Asperger syndrome were retrospectively reviewed. Forty percent of children with autism were diagnosed with epilepsy. Abnormal electroencephalograms and epilepsy occurred at significantly higher rates in children in the more impaired range of the autism spectrum (P<0.05). These findings suggest that the use of neurological investigative techniques such as electroencephalography should be a consequence of careful clinical evaluation and should be considered routinely during evaluation of more impaired individuals.

1H-Magnetic Resonance Spectroscopy Markers of Cognitive and Language Ability in Clinical Subtypes of Autism Spectrum Disorders

This study assessed metabolic functioning of regional brain areas to address whether there is a neurometabolic profile reflecting the underlying neuropathology in individuals with autism spectrum disorders, and if varied profiles correlate with the clinical subtypes. Thirteen children (7-16 years) with autism spectrum disorders and 8 typically developing children were compared on 1H-magnetic resonance spectroscopy data collected from hippocampus-amygdala and cerebellar regions. The autism spectrum disorder group had significantly lower N-acetyl-aspartate/creatine ratios bilaterally in the hippocampus-amygdala but not cerebellum, whereas myo-inositol/creatine was significantly increased in all measured regions. Choline/creatine was also significantly elevated in the left hippocampus-amygdala and cerebellar regions of children with autism spectrum disorder. Comparisons within the autism spectrum disorder group when clinically subdivided by history of speech delay revealed significant metabolic ratio differences. Magnetic resonance spectroscopy can provide important information regarding abnormal brain metabolism and clinical classification in autism spectrum disorders.

Subtyping Pervasive Developmental Disorder

The use of the diagnostic term pervasive developmental disorders (PDD), as well as the value and purpose of subtyping the PDD has been a controversial issue. Such subtyping has been particularly relevant to disorders that are considered to be in the higher-functioning range of PDD. This chapter presents the author’s own development of thought on this topic, and is divided into four main sections. The first is a selective review of opinion regarding the diagnosis of children with severe social withdrawal prior to the initial efforts of the American Psychiatric Association (1980,1987) to provide diagnostic criteria for this clinical spectrum. Focusing on some of the findings from a study addressing the validity of PDD subtypes, the second section considers the prevailing diagnostic system (APA, 1994). The third section discusses research findings and clinical examples that support or contradict the presently accepted subtyping. The chapter concludes with a brief review of the present state of knowledge with some consideration of the ongoing research questions and how this can enhance clinical practice for those assessing and treating young people with severe developmental/psychiatric disorders.

Minor Physical Anomalies as a Biologic Marker for Behavior Disorders

Abstract The presence of minor physical anomalies (MPA) has been proposed as a marker for abnormal fetal development occurring in the first trimester. Excess MPA are said to be particularly associated with childhood hyperactivity. This paper reviews clinical and research issues relating to MPA and describes their measurement in a mixed group of emotionally disturbed/behavior disordered children. This study confirms that MPA are associated with neurodevelopmental delay, which may underlie many types of child psychiatric disorders. Although the findings do not support the use of MPA scores for identification of high risk children, they remain an interesting research measure and a useful clinical indicator for developmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry , 1988, 27, 4:466–473.

A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder†

Autism spectrum disorder (ASD) is a severe developmental disorder of the central nervous system characterized by impairments in social interaction, communication, and range of interests and behaviors. The syndromes prevalence is estimated to be as high as 1 in 150 American children yet its etiology remains largely unknown. Examination of observed cytogenetic variants in individuals with ASD may identify genes involved in its pathogenesis. As part of a multidisciplinary study, an apparently balanced de novo translocation between chromosomes 2 and 9 [46,XY,t(2;9)(p13;p24)] was identified in a subject with pervasive developmental disorder not otherwise specified (PDD‐NOS), and no distinctive dysmorphic features. Molecular characterization of the rearrangement revealed direct interruption of the RAB11 family interacting protein 5 (RAB11FIP5) gene. RAB11FIP5 is a Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. It is ubiquitously expressed and reported to contribute to both neurotransmitter release and neurotransmitter uptake at the synaptic junction. Detailed analysis of the rearrangement breakpoints suggests that the reciprocal translocation may have formed secondary to incorrect repair of double strand breaks (DSBs) by nonhomologous end‐joining (NHEJ).

Brief Report: Stony Brook Guidelines on the Ethics of the Care of People with Autism and Their Families.

The increased prevalence of autism spectrum disorders (ASD), with associated societal and clinical impacts, calls for a broad community-based dialogue on treatment related ethical and social issues. The Stony Brook Guidelines, based on a community dialogue process with affected individuals, families and professionals, identify and discuss the following topics: treatment goals and happiness, distributive justice, managing the hopes for a cure, sibling responsibilities, intimacy and sex, diagnostic ethics, and research ethics. Our guidelines, based not on “top-down” imposition of professional expertise but rather on “bottom-up” grass roots attention to the voices of affected individuals and families speaking from experience, can inform clinical practice and are also meaningful for the wider social conversation emerging over the treatment of individuals with ASD.

A procedure for monitoring stimulant medication in hyperactive mentally retarded school children.

ABSTRACT Many hyperactive mentally retarded children in public school programs receive stimulant medication, but studies indicate that treatment monitoring practices are less than adequate. Standardized drug assessment instruments rarely are used, and the school typically plays a minor role in evaluating response to treatment. To improve upon this situation, a procedure developed originally for nonretarded children was adapted to evaluate drug effects in mentally retarded children in public school settings. This assessment procedure generates ecologically valid data, enables a high degree of precision in specifying target symptoms and measuring the magnitude of the therapeutic effect, and appears to generate useful information for making dosage adjustment decisions. Two case studies are presented to illustrate the use of this procedure and to highlight differences in the clinical utility of data from behavior rating scales versus direct observations. Although ratings and observations sometimes reveal similar dose-response profiles, the sole reliance on rating scales can lead to gross misperceptions of drug efficacy, even when the ratings are completed by highly motivated and cooperative teachers. Our experience in evaluating mentally retarded children supports (1) the value of assessment instruments designed specifically for this patient population (e.g., Aberrant Behavior Checklist), (2) the need for evaluating a broader range of target symptoms, and (3) the importance of being alert to the somewhat greater variability of responses to stimulant drugs in these children.

A Grassroots Community Dialogue on the Ethics of the Care of People with Autism and Their Families: The Stony Brook Guidelines

The increased recognition and reported prevalence of autism spectrum disorders (ASD) combined with the associated societal and clinical impact call for a broad grassroots community-based dialogue on treatment related ethical and social issues. In these Stony Brook Guidelines, which were developed during a full year of community dialogue (2010–2011) with affected individuals, families, and professionals in the field, we identify and discuss topics of paramount concern to the ASD constituency: treatment goals and happiness, distributive justice, managing the desperate hopes for a cure, sibling responsibilities, intimacy and sex, diagnostic ethics, and research ethics. The members of the dialogue core committee included doctors, ethicists, administrators, social workers, ministers, disability experts, and many family members of individuals with autism who were especially engaged in community activities on behalf of their constituency, including siblings, parents, and grandparents. Our guidelines are not based on “top-down” imposition of professional expertise, but rather on a “bottom-up” grass roots attention to the voices of affected individuals and families speaking from experience. These guidelines can inform clinical practice, but they also are meaningful for the wider social conversation emerging over the treatment of individuals with ASD.