Mohammad Ghaziuddin

Depression in Persons with Autism: Implications for Research and Clinical Care

Although several studies have investigated the occurrence of medical and neurological conditions in persons with autism, relatively few reports have focused on the phenomenology and treatment of psychiatric disorders in this population. There is emerging evidence that depression is probably the most common psychiatric disorder that occurs in autistic persons. In this review, we examine the factors that influence the presence of depression in this population, such as the level of intelligence, age, gender, associated medical conditions, and the role of genetic factors and life events. We discuss the various forms of treatment available and highlight the need for early detection.

Circulating autoantibodies to neuronal and glial filament proteins in autism

Autoimmunity may be a pathogenic factor in autism, a behavioral disorder of early childhood onset. Circulating autoantibodies are produced in organ-specific autoimmunity; therefore, we investigated them in the plasma of autistic subjects, mentally retarded (MR) subjects, and healthy controls. Autoantibodies (IgG isotype) to neuron-axon filament protein (anti-NAFP) and glial fibrillary acidic protein (anti-GFAP) were analyzed by the Western immunoblotting technique. We found a significant increase in incidence of anti-NAFP (P = .004) and anti-GFAP (P = .002) in autistic subjects, but not in MR subjects. Clinically, these autoantibodies may be related to autoimmune pathology in autism.

Defining the intellectual profile of Asperger Syndrome: comparison with high-functioning autism.

Asperger syndrome (AS) is a disorder of early childhood characterized by autistic social deficits, subtle communication impairment, and excessive isolated interests. There is no history of language delay or of mental retardation. Despite its increasing popularity as a distinct condition, its diagnostic validity remains uncertain. It is still unclear to what extent AS differs from autism with normal intelligence sometimes referred to as high-functioning autism (HFA). However, some reports have suggested that persons with AS possess a distinct profile on tests of intelligence characterized by a high verbal IQ and a low performance IQ, whereas in most cases with HFA, the pattern is reversed. Since few studies have directly compared AS subjects with HFA controls using unmodified diagnostic criteria and standardized measures of assessment, in this report we compared 22 AS subjects with 12 HFA controls, matched on age, sex and level of intelligence. As a group, subjects with AS showed a higher verbal IQ and higher scores on information and vocabulary subtests than those with HFA. However, scores of several AS and HFA subjects showed a mixed pattern. Implications of these findings are discussed in the context of the validity of Asperger Syndrome.

Pedantic Speaking Style Differentiates Asperger Syndrome from High-Functioning Autism.

Asperger syndrome (AS) is a pervasive developmental disorder recently introduced as a new diagnostic category in the ICD-10 and the DSM-IV. Along with motor clumsiness, pedantic speech has been proposed as a clinical feature of AS. However, few attempts have been made to define and measure this symptom. We studied 17 patients with AS (ICD-10; 14 male, 3 female; mean age 16.4 years, mean full-scale IQ 97) and compared them with a control group of 13 patients with normal-intelligence autism or high-functioning autism (HFA) (ICD-10/DSM-III-R; 12 male, 1 female; mean age 15.5 years, mean full-scale IQ 81.2). An operational definition of pedantic speech was formulated and a rating scale devised. 13 (76%) of the AS patients were rated as pedantic compared to 4 (31%) of the HFA group (χ2=6.3;p=.01). Results suggest that pedantic speech is common in AS and may help differentiate AS from high-functioning autism.

Depression in Children with Autism/Pervasive Developmental Disorders: A Case-Control Family History Study

Limited information is available about the occurrence of depression in children with autism and other pervasive developmental disorders (PDD). Although depression has been described in autistic children, questions about its validity have often been raised. One approach to address this issue is to investigate family histories of those autistic children diagnosed with clinical depression. Based on data available in nonautistic children, autistic children with depression would be expected to show an increased family history of depression. Since studies of this nature have not been attempted in autistic children, we compared the family history of 13 autistic/PDD children with depression (11 male; 2 female; M full-scale IQ 86.2, SD 24.2; M age 10.4 years, SD 2.2) with 10 autistic/PDD children without a history of current or previous depression (9 male; 1 female; M full-scale IQ 67, SD 12.9; M age 10.5 years, SD 1.6). Diagnosis of depression was based on the DSM-III-R criteria and confirmed independently by two psychiatrists. Ten (77%) of the depressed children had a positive family history of depression compared to 3 (30%) of the nondepressed group, t(21) = −2.4; p = .02. These findings lend support to the validity of depression as a distinct condition in some children with autism/PDD and suggest that, as in the normal population, autistic children who suffer from depression are more likely to have a family history of depression.

Asperger Syndrome: Tests of Right Hemisphere Functioning and Interhemispheric Communication

The primary aim of this investigation was to assess to what extent Rourkes (1989, 1995) nonverbal learning disabilities syndrome (NLD) model resembles the pattern of assets and deficits seen in people with Asperger syndrome (AS). NLD can be characterized by a cluster of deficits primarily affecting nonverbal aspects of functioning, in the presence of proficiency in single word reading and a superior verbal memory. The neurological underpinnings of this syndrome may be dysfunction of white matter affecting right hemisphere functioning and interhemispheric communication. To explore this hypothesis, eight participants with AS (ages 10 to 41 years) were assessed in the following areas: the pragmatics of language and communication, verbal and visual memory, visual-spatial abilities, and bimanual motor skills. Results confirmed the close similarity in the neuropsychologic profiles of NLD and AS.

Asperger Syndrome: Associated Psychiatric and Medical Conditions

Asperger syndrome (AS) is a pervasive developmental disorder characterized by social dysfunction and idiosyncratic interests in the presence of normal intelligence. There is no history of language delay. Persons with AS are often described as being active but odd, with a pedantic manner of speaking. In addition, they often present with a variety of medical and psychiatric conditions, a topic that has not received systematic study. This review summarizes the literature on this topic, with particular reference to publications in the last two decades. The purpose is to underscore the need for early identification and treatment of these conditions.

Cytogenetic and molecular analysis of inv dup(15) chromosomes observed in two patients with autistic disorder and mental retardation

A variety of distinct phenotypes has been associated with supernumerary inv dup(15) chromosomes. Although different cytogenetic rearrangements have been associated with distinguishable clinical syndromes, precise genotype-phenotype correlations have not been determined. However, the availability of chromosome 15 DNA markers provides a means to characterize inv dup(15) chromosomes in detail to facilitate the determination of specific genotype-phenotype associations. We describe 2 patients with an autistic disorder, mental retardation, developmental delay, seizures, and supernumerary inv dup(15) chromosomes. Conventional and molecular cytogenetic studies confirmed the chromosomal origin of the supernumerary chromosomes and showed that the duplicated region extended to at least band 15q13. An analysis of chromosome 15 microsatellite CA polymorphisms suggested a maternal origin of the inv dup(15) chromosomes and biparental inheritance of the two intact chromosome 15 homologs. The results of this study add to the existing literature which suggests that the clinical phenotype of patients with a supernumerary inv dup(15) chromosome is determined not only by the extent of the duplicated region, but by the dosage of genes located within band 15q13 and the origin of the normal chromosomes 15.

Life events and depression in children with pervasive developmental disorders

To determine the role of life events in the occurrence of depression in children with pervasive developmental disorders (PDD), we compared 11 patients (DSM-III-R; 9 male; 2 female; Mage: 11.0 years; Mfull-scale IQ: 75.3) with PDD and depression, with an age- and sex- matched control group of patients with PDD without depression (DSM-III-R; 9 male; 2 female; Mage: 9.8 years; Mfull-scale IQ: 60.6). Information was collected about the occurrence of unpleasant life events in the 12 months prior to the onset of depression. Depressed children experienced significantly more life events in the 12 months prior to the onset of depression. Exit events such as bereavement were more common in the depressed group. Findings suggest that, as in the general population, significant life events, particularly those with a negative impact, may contribute to the occurrence of depression in children with PDD. Future studies should explore the role of both biologic factors and environmental Stressors in the onset of depression in this population.

Brief Report: Should the DSM V Drop Asperger Syndrome?

The DSM IV defines Asperger syndrome (AS) as a pervasive developmental (autistic spectrum) disorder characterized by social deficits and rigid focused interests in the absence of language impairment and cognitive delay. Since its inclusion in the DSM-IV, there has been a dramatic increase in its recognition both in children and adults. However, because studies have generally failed to demonstrate a clear distinction between AS and autism, some researchers have called for its elimination from the forthcoming DSM V. This report argues for a modification of its diagnostic criteria and its continued retention in the diagnostic manual.