Auditory brainstem evoked responses in autistic children.

Auditory brainstem evoked responses (ABRs) were studied in 16 autistic children. Three children had severe delays in wave I latency, indicating defective functioning of the peripheral auditory pathway. The remaining subjects also had delayed wave I latency but only for right ear stimulation at the lowest stimulus intensity. Eight autistic children (and no control subjects) had ABR transmission time values 3 SDs beyond the normal mean, suggesting auditory processing defects peripheral to or within the brainstem auditory pathway. These findings (1) may have no causal relationship to the child's autistic handicaps, (2) may represent distortions in auditory input that impair the learning of language, and (3) may reflect an earlier state in which abnormal input directly caused maldevelopment of forebrain systems necessary for language and cognitive function.

An intervention to improve the reliability of manuscript reviews for the Journal of the American Academy of Child and Adolescent Psychiatry.

OBJECTIVE: The effects of methods used to improve the interrater reliability of reviewers' ratings of manuscripts submitted to the Journal of the American Academy of Child and Adolescent Psychiatry were studied. METHOD: Reviewers' ratings of consecutive manuscripts submitted over approximately 1 year were first analyzed; 296 pairs of ratings were studied. Intraclass correlations and confidence intervals for the correlations were computed for the two main ratings by which reviewers quantified the quality of the article: a 1-10 overall quality rating and a recommendation for acceptance or rejection with four possibilities along that continuum. Modifications were then introduced, including a multi-item rating scale and two training manuals to accompany it. Over the next year, 272 more articles were rated, and reliabilities were computed for the new scale and for the scales previously used. RESULTS: The intraclass correlation of the most reliable rating before the intervention was 0.27; the reliability of the new rating procedure was 0.43. The difference between these two was significant. The reliability for the new rating scale was in the fair to good range, and it became even better when the ratings of the two reviewers were averaged and the reliability stepped up by the Spearman-Brown formula. The new rating scale had excellent internal consistency and correlated highly with other quality ratings. CONCLUSIONS: The data confirm that the reliability of ratings of scientific articles may be improved by increasing the number of rating scale points, eliciting ratings of separate, concrete items rather than a global judgment, using training manuals, and averaging the scores of multiple reviewers.

Reliability of the Part II board certification examination in psychiatry: examination stability.

OBJECTIVE: The aim of this study was to examine the reliability (examination stability) of the American Board of Psychiatry and Neurology (ABPN) Part II (oral) examination in psychiatry. METHOD: The authors analyzed the consistency (agreement between grades given by two independent examiners) for a 1-year examination cycle using a weighted kappa statistic and compared different parts of the examination (live patient and videotape), different examination sites, different days, and different times of the day. RESULTS: There was no significant difference in agreement between examiners by different parts of the examination, examination site, day of the week, or time of day. CONCLUSIONS: The stability of the Part II ABPN examination in psychiatry is not influenced significantly by the format or site of administration. Candidate performance is the predominant factor in the determination of passing or failing grades.

Reliability of the Part II Board Certification Examination in Psychiatry: interexaminer consistency.

OBJECTIVE: The aim of the study was to examine the reliability (interexaminer consistency) of the American Board of Psychiatry and Neurology (ABPN) Part II (oral) examination in psychiatry. METHOD: Grades were assigned independently by two examiners who observed the same examination in a 1-year cycle (1,422 candidates, two examinations each). The consistency between these pairs of grades (pass, condition, fail) was analyzed using a weighted kappa statistic. RESULTS: There was perfect agreement between examiners in 67% of examinations, minor disagreement in 26%, and major disagreement in 7% (weighted kappa = 0.54-0.56). CONCLUSIONS: The Part II ABPN examination demonstrates fair to good reliability as measured by interexaminer consistency. Development of more explicit grading criteria should further improve examiner agreement in future examinations.

Positron emission tomography of the cerebellum in autism.

On the basis of neurological evidence that autistic patients have fewer Purkinje and granule cells in the cerebellum as well as vermal cerebellar hypoplasia, the authors tested the hypothesis that autistic patients have cerebellar hypofunctioning. They used positron emission tomography of the cerebellum with 18F-labeled 2-deoxyglucose to study seven autistic patients and eight age-matched control subjects. The results showed no significant difference in mean cerebellar glucose metabolism between the two groups, but all mean glucose rates of the autistic patients were either equal to or greater than those of the control subjects. The implications of these findings are discussed.

Autism, affective disorders, and social phobia.

The purpose of this study is to test the hypothesis that major affective and/or anxiety disorders are increased among relatives of autistic probands compared with controls. Among 36 families with an autistic child, 23 (64%) have a first degree relative diagnosed with major depressive disorder and 14 (39%) have a first degree relative diagnosed with social phobia. These rates are significantly greater than the 19% and 5%, respectively, found among 21 families with a child having a genetic condition, tuberous sclerosis complex, or a seizure disorder but no autism. The frequency of major depression among the 96 first degree relatives of autistic probands is 37.5% compared with 11.1% found among 45 relatives of control probands. The frequency of social phobia, 20.2%, is approximately 10 times more common than that found among the relatives of the control probands (2.4%). Elevated rates of both major depression and social phobia are found among parents and siblings in the families with an autistic child. Furthermore, 64% of parents affected with a major depression had the onset of the first depressive episode prior to the birth of the autistic child and all parents with social phobia had the onset of condition prior to the birth of the autistic child. Family patterns differ depending on the intellectual level of the autistic child; specifically, social phobia is significantly greater among the first degree relatives of non-retarded autistic probands than among relatives of individuals with autism and comorbid mental retardation.(ABSTRACT TRUNCATED AT 250 WORDS)

Pervasive developmental disorders: a 10-year review.

OBJECTIVE: To summarize recent advances about the nature, diagnosis, and treatment of pervasive developmental disorders. METHOD: Review of Medline databases, books, and book chapters published between July 1989 and November 1999. RESULTS: Clinical and genetic studies support expansion of the concept of autism to include a broader spectrum of social communication handicaps. The prevalence of autism is approximately 1 per 2,000; the prevalence of autism and Asperger's disorder together is 1 per 1,000. The Checklist for Autism in Toddlers is a useful screening instrument for 18-month-old children; the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule are instruments of choice for research. Although twin and family studies clearly support genetic factors as important in autism, linkage analysis studies indicate that many genes may be involved. There is no one treatment of choice. Social-pragmatic approaches, augmented by individualized strategies and social coaching, may be best for teaching social communication skills. Pharmacological interventions have a limited role in improving social communication, but selective serotonin reuptake inhibitors and atypical neuroleptic medications may help ameliorate aggression, hyperactivity, and other secondary problems. CONCLUSIONS: Private and government agencies must continue to support basic and applied research.

Case study: the use of melatonin in a boy with refractory bipolar disorder.

The authors describe the clinical course of a 10-year-old boy with bipolar disorder diagnosed at age 5 years. Lithium, carbamazepine, and valproic acid were ineffective or caused intolerable side effects. A trial of melatonin led to rapid relief of insomnia and aborted a manic episode. He has continued to take melatonin and adjunctive alprazolam for 15 months without recurrence of insomnia or mania. Affective disorders involving circadian dysregulation may respond to interventions that restore a normal sleep-wake cycle. Literature supporting this hypothesis is cited.

A dimensional classification of autism spectrum disorder by social communication domains.

OBJECTIVE: To investigate whether "social communication" could be used to assess severity of symptoms in autism spectrum disorder. Social communication refers to the communication of cognitive and emotional information through facial expression, gesture, and prosody and through implicit understanding of pragmatics and of theory of mind. METHOD: Subjects were evaluated by raters using the Autism Diagnostic interview-Revised and either the Autism Diagnostic Observation Schedule or the Pre-Linguistic Autism Diagnostic Observation Schedule. Two investigators independently diagnosed autism, Asperger's disorder, or pervasive developmental disorder-not otherwise specified in 63 subjects. Items from the Autism Diagnostic Interview-Revised that were judged to represent social communication behaviors were factor-analyzed. RESULTS: Three factors were identified: affective reciprocity, joint attention, and theory of mind. Comparing this new classification approach to DSM-IV led to suggestions for possible changes in the latter: (1) Vocabulary and grammar deficiencies in autistic persons should be coded under developmental language disorder, (2) The diagnosis of Asperger's disorder may not be needed. (3) Requiring that all persons with autism spectrum disorder have a symptom from the "restrictive, repetitive, and stereotypic" list may need to be reconsidered. CONCLUSIONS: The DSM-IV category of pervasive developmental disorder may be ideal for diagnosing "classic" autism, but it may be inadequate for diagnosing less severe forms of the disorder.

A study of the Board Certification Examination in Child and Adolescent Psychiatry.

In 1977, training directors of 55 child psychiatry training programs agreed to provide the Committee on Certification in Child Psychiatry of the American Board of Psychiatry and Neurology, Inc. with confidential data about the clinical performance of each of their graduates in 1978, 1979, and 1980. Information about 267 graduates from 37 programs was received. Almost all programs were university affiliated and located in medical centers. By 1986, 112 of these graduates had taken the child aboard examination. Training director ratings were found to be statistically correlated to a significant degree with actual pass or fail results on the written and on the overall examination.

Practice parameters for the assessment and treatment of children, adolescents, and adults with autism and other pervasive developmental disorders. American Academy of Child and Adolescent Psychiatry Working Group on Quality Issues.

Autism and the related pervasive developmental disorders are characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills, which arise in the first years of life. Although frequently associated with mental retardation, these conditions are distinctive in terms of their course and treatment. These conditions have a wide range of syndrome expression, and their management presents particular challenges for clinicians. Individuals with these conditions can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with these conditions often require the care of multiple providers; coordination of services and advocacy for individuals and their families is important. Early, sustained intervention is indicated, as is the use of various treatment modalities (e.g., pharmacotherapy, special education, speech/communication therapy, and behavior modification).

Summary of the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults with Autism and other Pervasive Developmental Disorders. American Academy of Child and Adolescent Psychiatry.

This summary provides an overview of the assessment and treatment recommendations contained in the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults With Autism and Other Pervasive Developmental Disorders. The parameters were written to aid clinicians in the assessment and treatment of children and adolescents with autism and other pervasive developmental disorders. Autism and the related pervasive developmental disorders are characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills, which arise in the first years of life. Although frequently associated with mental retardation, these conditions are distinctive in terms of their course and treatment. These conditions have a wide range of syndrome expression, and their management presents particular challenges for clinicians. Individuals with these conditions can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with these conditions often require the care of multiple providers; coordination of services and advocacy for individuals and their families is important. Early, sustained intervention is indicated, as is the use of various treatment modalities (e.g., pharmacotherapy, special education, speech/communication therapy, and behavior modification.

Domains of social communication handicap in autism spectrum disorder.

OBJECTIVE: To investigate whether specific "social communication" handicaps could be identified in autism spectrum disorder using the Autism Diagnostic Observation Schedule and to compare the results with those found in a previous factor-analysis study using the Autism Diagnostic Interview-Revised. METHOD: All subjects were evaluated with both instruments. J.R. and P.E.T. independently diagnosed autism, Asperger's disorder, or pervasive developmental disorder--not otherwise specified in 51 children. Items from the Autism Diagnostic Observation Schedule that represented social communication behaviors were factor-analyzed. RESULTS: Three factors were identified: joint attention, affective reciprocity, and theory of mind. These are the same social communication domains that were identified in the previous study. CONCLUSIONS: These 3 social communication domains have been discussed in the literature regarding normal development and in previous research on autism spectrum disorders. If these domains are replicated in larger sample sizes, they could be used to monitor the results of pharmacological and psychotherapeutic interventions in autism spectrum disorders.

The Kiddie Formal Thought Disorder Rating Scale: clinical assessment, reliability, and validity.

The Kiddie Formal Thought Disorder Story Game and the Kiddie Formal Thought Disorder Scale were administered to schizophrenic, schizotypal, and normal children, aged 5 to 13 years. The story game elicited more elaborate speech samples than did a structural clinical interview focused on psychotic symptomatology. The sum of illogical thinking and loose associations was a reliable kappa = 0.77), sensitive (79%), and specific (90%) indicator of schizophrenia in this sample. It also demonstrated significant developmental changes in the schizophrenic and normal subjects. Incoherence and poverty of content of speech were infrequently rated in both schizophrenic and normal subjects.

Electroencephalographic and reaction time asymmetries to musical chord stimuli.

EEG was recorded over left and right hemispheres at temporal leads (T3, T4) referred to the vertex (Cz) in 16 right-handed male subjects. Musical chords were presented randomly in monaural sequence, during a task which required a selective motor response to stimuli presented to one ear. The integrated amplitude of the 8-13 Hz alpha rhythm was measured when subjects listened passively. Under all conditions, a lower mean alpha amplitude was recorded over the right hemisphere than the left, regardless of which ear was stimulated. Alpha suppression over the right temporal area was accentuated when the performance task directed attention to the stimulus. Reaction time to left ear stimulation was shorter than that for the right ear. With monaural stimulus presentation behavioral asymmetry, and various EEG asymmetries can be observed. There is hemispheric asymmetry associated with attention to task relevant stimuli indicated by reduction in the alpha rhythm over the right temporal area and asymmetry in reaction time with greater efficiency of the left ear to muscial chords.

Effects of afternoon naps on physiological variables performance and self-reported activation.

Fluctuations in physiological variables resulting from naps and the relationship of these to previously studies changes in performance and subjective activation associated with napping were examined. The subjects were eighteen healthy male university students who habitually slept 1/2-2 hr in the afternoon. Measurements were obtained of our physiological variables, from a continuous 10-min auditory reaction time task and two factors of an Activation. Deactivation Adjective Checklist 20 min before and after a control condition and two electroencephalographically recorded afternoons of sleep. The experimental conditions comprised a 2-hr period of wakefulness, a 1/2 hr nap from 4.35-5.05 p.m., and a 2-hr nap from 3.05-5.05 p.m. Following each sleep treatment, when compared with the control condition, there were statistically significant shifts of improved reaction time performance, and elevated activation as reflected by the two self-report scales, inceased EEG frequency, heart rate, and electrodermal responses. The shifts of increased behavioral efficiency, subjective and physiological activation were approximately equivalent in extent between 2-hr and 1/2-hr naps. These findings indicate that besides the previously reported facilitation by naps of performance and mood, physiological activation is increased following accustomed episodes of afternoon sleep.

Electrophysiological studies of autism: the whisper of the bang.

Many neurophysiological hypotheses have focused upon the level of the central nervous system at which abnormal neural function may be present. Although some have argued that the type of language and cognitive defects shown by autistic children almost certainly reflects forebrain dysfunctions, current studies point to the possibility that some autistic children may have dysfunction of neural systems in the brainstem. One interpretation of these findings is that such abnormalities, occurring during a critical phase of early postnatal development, might themselves have acted directly as neuropathological agents, adversely influencing developing forebrain systems. A model for such an event has already been identified in animal research. If this be true, neurobiologists may not necessarily be identifying what is current pathology but may only be seeing a reflection of abnormal neural factors that once were important in development of the syndrome. Such a possibility suggests that investigators should consider extending their current studies to include young normal children as well as children with prototypic signs of abnormal language and interpersonal development.

Autism and tuberous sclerosis.

Autism is a behavior disorder with genetic influences indicated from twin and family studies and from the co-occurrence of autism with known genetic disorders. Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral manifestations including autism. A literature review of these two disorders substantiates a significant association of autism and TSC with 17-58% of TSC subjects manifesting autism and 0.4-3% of autistic subjects having TSC. In initial data collected on 13 TSC probands and 14 autistic probands in our family study of autism and TSC, we identified 7 TSC subjects with autism. The seven TSC autistic probands are similar to non-TSC autistic probands on the Social and Communication domains of the Autism Diagnostic Inventory (ADI) (Le Couteur et al., 1989), but show fewer Repetitive Rituals. There are more male TSC probands with autism than female, despite an equal sex ratio among TSC probands. The TSC probands with autism have significantly more seizures and mental retardation than those without autism; however, the extent and etiology of associations require further study. Our preliminary findings suggest that a fruitful approach for delineating genetic influences in autism may come from further investigation of possible mechanisms underlying the association of autism and TSC.

Autism in tuberous sclerosis complex.

The frequency and clinical presentation of autism in 28 probands with tuberous sclerosis complex (TSC) are reported and risk factors that may influence the development of autism in TSC are examined. Eight probands meet ICD-10 and DSM-IV criteria for autism, an additional 4 meet criteria for pervasive developmental disorder (PDD). Twelve TSC probands with autism/PDD are compared to 16 TSC probands without these conditions for factors which may underlie the association of autism and TSC. A specific seizure type, infantile spasms, as well as mental retardation, are increased in the TSC, autistic/PDD group. Furthermore, rates of social phobia and substance abuse are elevated among first-degree relatives of TSC probands with autism compared to first-degree relatives of TSC probands without autism. Implications of these findings in understanding the association of autism and TSC are discussed.

Parental reproductive problems and gestational hormonal exposure in autistic and schizophrenic children.

The incidence of infertility and two or more spontaneous abortions was significantly increased in the parents, compared to that reported for the general population, in this pilot survey of 61 patients evaluated for major childhood psychoses. In addition, 18% of our patients had a history of early gestational exposure to progesterone/estrogen compounds (9 patients) and to cortisone (2 patients). This frequency of gestational hormoné exposure was significantly increased over that in normal infants from three published surveys. However, in 5 of the 11 patients with gestational hormonal exposure, the medication was prescribed because of prior parental reproductive problems or bleeding during the current pregnancy. Therefore, it cannot be concluded that the gestational hormonal exposure was causally related to the psychoses present in these patients. In order to obtain more conclusive data, there will need to be continued monitoring of parental reproductive histories and gestational environmental exposures in autistic and schizophrenic children.