Ira L. Cohen

A Comparison of Haloperidol and Behavior Therapy and Their Interaction in Autistic Children

Abstract Haloperidol and behavior therapy, and the interaction of the two treatments were critically assessed with respect to their effects on symptoms and language acquisition in 40 autistic children aged 2.6 to 7.2 years. The children were randomly assigned to four treatment groups in a factorial design. The study was placebo controlled and double-blind, using multiple independent raters who assessed treatment effects under three types of rating conditions. Haloperidol was found to be significantly superior to placebo in decreasing certain symptoms, depending on the age group. The combination of the two treatments was most effective in facilitating the acquisition of imitative speech. Optimal dosage of haloperidol ranged from 0.5 to 4.0 mg./day; the most common untoward effect was excessive sedation, which was clearly a function of dosage.

The PDD Behavior Inventory: A Rating Scale for Assessing Response to Intervention in Children with Pervasive Developmental Disorder

The PDD Behavior Inventory (PDDBI) is a rating scale filled out by caregivers or teachers that was designed to assess children having a Pervasive Developmental Disorder (PDD; autism, Asperger disorder, PDD-NOS, or childhood disintegrative disorder). Both adaptive and maladaptive behaviors are assessed in the scale, making it useful for treatment studies in which decreases in maladaptive behaviors and improvements in adaptive social and language skills relevant to PDD are expected. The adaptive behaviors assessed include core features of the disorder such as joint attention skills, pretend play, and referential gesture. The maladaptive behaviors sample a wide variety of behaviors observed in both lower- and higher-functioning individuals and include stereotyped behaviors, fears, aggression, social interaction deficits, and aberrant language. The inventory was found to have a high degree of internal consistency. Inter-rater reliability was better for adaptive behaviors than for maladaptive behaviors. Factor analyses confirmed the structure of the PDDBI and indicated good construct validity. In a subsample of children between 3 and 6 years of age, raw scores for adaptive behaviors increased with age in the parent and teacher versions, as did measures of social pragmatic problems. It was concluded that the PDDBI is both reliable and valid and is useful in providing information not typically available in most instruments used to assess children with PDD.

Drugs in Aggressive Behavior

The role of pharmacotherapy in the management of severe aggressive behavior in children is reviewed. An overview of the relevant literature, a discussion of methodological issues, and a description of a pilot study of the comparative efficacy of lithium, haloperidol, and chlorpromazine are presented. It is concluded that this area has not been studied systematically and that, in the future, research must be directed toward assessing the value of current and new pharmacological agents by using well-defined patient populations and attempting to identify subgroups of responders and nonresponders. Equally important are studies concerned with an evaluation of pharmacotherapy combined with psychosocial treatments. Lithium and haloperidol appear worthy of critical examination as adjuncts in the treatment of children for whom the long-term prognosis is poor. Journal of the American Academy of Child Psychiatry , 21, 2:107–117, 1982.

Criterion-Related Validity of the PDD Behavior Inventory

The PDD Behavior Inventory (PDDBI) is a rating scale filled out by parents and teachers that is designed to assess response to intervention in children with PDD. It consists of subscales that measure both maladaptive and adaptive behaviors and also provides a summary “Autism Score” reflective of the severity of the condition. The scale has been shown to have very good internal consistency as well as developmental and construct validity. In this study, the PDDBIs criterion-related validity was assessed. Correlations with the Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised were good. Selected maladaptive scales from the PDDBI correlated well with comparable factors of the Nisonger Child Behavior Rating Form. The adaptive sections of the PDDBI correlated highly with the Griffiths Mental Development Scales and with the Vineland Adaptive Behavior Scales. These results confirm the validity of the PDDBI and suggest that the scale will have value in assessing treatment-related changes in maladaptive and adaptive behaviors associated with PDD.

18-month predictors of later outcomes in Younger siblings of children with autism spectrum disorder: A baby siblings research consortium study

OBJECTIVE Younger siblings of children with autism spectrum disorder (ASD) are at high risk (HR) for developing ASD as well as features of the broader autism phenotype. Although this complicates early diagnostic considerations in this cohort, it also provides an opportunity to examine patterns of behavior associated specifically with ASD compared to other developmental outcomes. METHOD We applied Classification and Regression Trees (CART) analysis to individual items of the Autism Diagnostic Observation Schedule (ADOS) in 719 HR siblings to identify behavioral features at 18 months that were predictive of diagnostic outcomes (ASD, atypical development, and typical development) at 36 months. RESULTS Three distinct combinations of features at 18 months were predictive of ASD outcome: poor eye contact combined with lack of communicative gestures and giving; poor eye contact combined with a lack of imaginative play; and lack of giving and presence of repetitive behaviors, but with intact eye contact. These 18-month behavioral profiles predicted ASD versus non-ASD status at 36 months with 82.7% accuracy in an initial test sample and 77.3% accuracy in a validation sample. Clinical features at age 3 years among children with ASD varied as a function of their 18-month symptom profiles. Children with ASD who were misclassified at 18 months were higher functioning, and their autism symptoms increased between 18 and 36 months. CONCLUSION These findings suggest the presence of different developmental pathways to ASD in HR siblings. Understanding such pathways will provide clearer targets for neural and genetic research and identification of developmentally specific treatments for ASD.

Early Medical and Behavioral Characteristics of NICU Infants Later Classified With ASD

OBJECTIVES: Recent evidence suggests higher prevalence of autism spectrum disorder (ASD) in NICU graduates. This aim of this study was to identify retrospectively early behaviors found more frequently in NICU infants who went on to develop ASD. METHODS: Twenty-eight NICU graduates who later received a diagnosis of ASD were compared with 2169 other NICU graduates recruited from 1994 to 2005. They differed in gender, gestational age, and birth cohort. These characteristics were used to draw a matched control sample (n = 112) to determine which, if any, early behaviors discriminated subsequent ASD diagnosis. Behavioral testing at targeted ages (adjusted for gestation) included the Rapid Neonatal Neurobehavioral Assessment (hospital discharge, 1 month), Arousal-Modulated Attention (hospital discharge, 1 and 4 months), and Bayley Scales of Infant Development (multiple times, 4–25 months). RESULTS: At 1 month, children with ASD but not control children had persistent neurobehavioral abnormalities and higher incidences of asymmetric visual tracking and arm tone deficits. At 4 months, children with ASD had continued visual preference for higher amounts of stimulation than did control children, behaving more like newborns. Unlike control children, children with ASD had declining mental and motor performance by 7 to 10 months, resembling infants with severe central nervous system involvement. CONCLUSIONS: Differences in specific behavior domains between NICU graduates who later receive a diagnosis of ASD and matched NICU control children may be identified in early infancy. Studies with this cohort may provide insights to help understand and detect early disabilities, including ASD.

Case study: deterioration, autism, and recovery in two siblings.

Two siblings whose functioning deteriorated in the second year of life met criteria for autism. They recovered after a form of behavior modification that was successful in a previous study. Follow-up of that study and of the siblings demonstrated that recovery was enduring. It is hypothesized that such therapy succeeds by modifying a still-plastic neural circuitry.

Autism severity is associated with child and maternal MAOA genotypes.

Cohen IL, Liu X, Lewis MES, Chudley A, Forster‐Gibson C, Gonzalez M, Jenkins EC, Brown WT, Holden JJA. Autism severity is associated with child and maternal MAOA genotypes.

Some physical parameters of young autistic children.

Abstract This paper provides information relevant to growth and development in a sample (N = 101) of young autistic children. Though birth weights of patients did not deviate from normative findings or from those of their own siblings, the distribution of heights between ages 2 and 7 years was significantly different from the normal population. Certain additional measures were available in a subgroup of patients: severity of illness and blood lead levels were negatively correlated with language DQ and IQ levels. A significant number had elevated T 3 and T 4 levels, and the latter were positively correlated with minor physical anomaly scores. These results are discussed as they relate to the concepts of biological age and hypothalamic dysfunction.

Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum

IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.ConclusionsThe observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.