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PubMed2006

Agreement among four diagnostic instruments for autism spectrum disorders in toddlers.

Autistic spectrum disorders (ASD) can be difficult to diagnose in toddlers. This study compared diagnostic measures (ADOS-G, ADI-R, CARS, and clinical judgment using DSM-IV criteria) applied to toddlers. Results indicated that the ADOS-G, CARS, and clinical judgment agreed with each other but not with the ADI-R. Many of the children classified with ASD by the other measures were not classified with autism by the ADI-R because they did not display enough repetitive behaviors and stereotyped interests. These results indicate that young children with ASD may not display repetitive behaviors and stereotyped interests, and for toddlers, the ADI-R would have a higher sensitivity if revised to include a diagnosis of PDD-NOS, for which the requirement of repetitive behaviors is less stringent.

Autistic Disorder↗

PubMedDate not supplied

[Asperger's syndrome--a separate nosologic entity or part of the spectrum of autism].

This paper describes Asperger's syndrome, a disease similar to the autistic disorder, delineated for the first time by Asperger in 1944, just a few months after L. Kanner described infantile autism. Although, according to the epidemiological data, it occurs far more frequently than infantile autism, in practice this diagnosis is rarely established. Asperger's syndrome is defined as autistic syndrome among children with relatively high degree of intellectual functions, with marked disorder of speech and motoricity and interest confined to a very specified area. Learning is mechanical and routine and games uninventive. Children lack the need for age peer company. Boys are affected ten times more frequently than girls.

Autistic Disorder↗

PubMed2003

Necdin-related MAGE proteins differentially interact with the E2F1 transcription factor and the p75 neurotrophin receptor.

Necdin is a growth suppressor expressed predominantly in postmitotic neurons and implicated in their terminal differentiation. Necdin shows a moderate homology to the MAGE family proteins, the functional roles of which are largely unknown. Human genes encoding necdin, MAGEL2 (necdin-like 1), and MAGE-G1 (necdin-like 2) are located in proximal chromosome 15q, a region associated with neurodevelopmental disorders such as Prader-Willi syndrome, Angelman syndrome, and autistic disorder. The necdin and MAGEL2 genes are subjected to genomic imprinting and suggested to be involved in the etiology of Prader-Willi syndrome. In this study, we compared biochemical and functional characteristics of murine orthologs of these necdin-related MAGE proteins. The colony formation and bromodeoxyuridine incorporation analyses revealed that necdin and MAGE-G1, but not MAGEL2, induced growth arrest. Necdin and MAGE-G1 interacted with the transcription factor E2F1 via its transactivation domain, repressed E2F1-dependent transcription, and antagonized E2F1-induced apoptosis of N1E-115 neuroblastoma cells. In addition, necdin and MAGE-G1 interacted with the p75 neurotrophin receptor via its distinct intracellular domains. In contrast, MAGEL2 failed to bind to these necdin interactors, suggesting that MAGEL2 has no necdin-like function in developing brain. Overexpression of p75 translocated necdin and MAGE-G1 in the proximity of the plasma membrane and reduced their association with E2F1 to facilitate E2F1-induced death of neuroblastoma cells. These results suggest that necdin and MAGE-G1 target both E2F1 and p75 to regulate cell viability during brain development.

Animals↗

PubMed2006

Developmental cognitive genetics: how psychology can inform genetics and vice versa.

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.

Child↗

PubMed2002

Autism: a medical primer.

Autistic disorder, a pervasive developmental disorder resulting in social, language, or sensorimotor deficits, occurs in approximately seven of 10,000 persons. Early detection and intervention significantly improve outcome, with about one third of autistic persons achieving some degree of independent living. Indications for developmental evaluation include no babbling, pointing, or use of other gestures by 12 months of age, no single words by 16 months of age, no two-word spontaneous phrases by 24 months of age, and loss of previously learned language or social skills at any age. The differential diagnosis includes other psychiatric and pervasive developmental disorders, deafness, and profound hearing loss. Autism is frequently associated with fragile X syndrome and tuberous sclerosis, and may be caused by lead poisoning and metabolic disorders. Common comorbidities include mental retardation, seizure disorder, and psychiatric disorders such as depression and anxiety. Behavior modification programs are helpful and are usually administered by multidisciplinary teams, targeted medication is used to address behavior concerns. Many different treatment approaches can be used, some of which are unproven and have little scientific support. Parents may be encouraged to investigate national resources and local support networks.

Autistic Disorder↗

PubMed2004

The clinical necessity for assessing Attention Deficit/Hyperactivity Disorder (AD/HD) symptoms in children with high-functioning Pervasive Developmental Disorder (PDD).

Although the DSM-IV diagnostic criteria for Attention Deficit/Hyperactivity Disorder (AD/HD) exclude Pervasive Developmental Disorder (PDD), some clinicians find that the two disorders can be comorbid and, in fact, make a dual diagnosis. Nevertheless, few empirical studies have investigated the clinical necessity for this practice. In the first of our two studies, children with high-functioning PDD were selected from among 520 outpatients. Of these, children also meeting the DSM-IV criteria for AD/HD were identified through a psychologist's observation, the completion of the ADHD-Rating Scale by parents and/or teachers, and a child psychiatrist's examination. We then examined the impact of PDD subtype and age on the co-occurrence rate. Study 2 analyzed comorbidity in two cases taken from Study 1. Of the 53 subjects in Study 1, 36 children also met the DSM-IV criteria for AD/HD. The co-occurrence rate for Asperger's Disorder (AS)/Pervasive Developmental Disorder, Not Otherwise Specified (PDDNOS) (85%) was significantly higher than for Autistic Disorder (57.6 %), and AD/HD symptoms were more common in younger children. Study 2 demonstrated the existence of comorbidity of PDD and AD/HD as separate disorders. We conclude not only that AD/HD symptoms occur frequently in children with PDD, but also that in some cases a dual diagnosis is essential to the implementation of effective treatment.

Adolescent↗

PubMed1999

Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study.

This pilot study examined the efficacy and tolerability of olanzapine in the treatment of children, adolescents, and adults with pervasive developmental disorders (PDDs). Eight patients with principal diagnoses (DSM-IV) of autistic disorder (N = 5) or PDD not otherwise specified (N = 3) were given olanzapine in an open-label, prospective fashion for 12 weeks. Clinical ratings were obtained at baseline and at the end of weeks (EOWs) 4, 8, and 12. Seven of eight patients completed the 12-week trial, and six of the completers were deemed clinical responders as measured by ratings at the EOW 12 of "much improved" or "very much improved" on the global improvement item of the Clinical Global Impression Scale. Significant improvements in overall symptoms of autism, motor restlessness or hyperactivity, social relatedness, affectual reactions, sensory responses, language usage, self-injurious behavior, aggression, irritability or anger, anxiety, and depression were observed. Significant changes in repetitive behaviors were not observed for the group. The EOW 12 mean +/- SD daily dose of olanzapine was 7.8 +/- 4.7 mg/day. The drug was well tolerated with the most significant adverse effects noted to be increased appetite and weight gain in six patients and sedation in three. With respect to weight gain, the mean +/- SD weight for the group increased from 137.50 +/- 55.81 pounds (62.50 +/- 25.37 kilograms) at baseline to 155.94 +/- 55.13 pounds (70.88 +/- 25.06 kilograms) at EOW 12. No evidence of extrapyramidal side effects or liver function abnormalities was seen. These preliminary results suggest that olanzapine may be an effective and well tolerated drug in targeting core and related symptoms of PDDs in children, adolescents, and adults. Further studies, particularly those that are placebo-controlled and double-blinded, are indicated to better define the clinical use of olanzapine in these patient populations.

Adolescent↗

PubMed1997

Autism and Asperger's syndrome.

Knowledge about the spectrum of autistic disorders, including Asperger's syndrome, has grown significantly. Diagnoses can be made more reliably and there is better characterization of elements within the spectrum than ever before. A clearer picture of the cognitive limitations displayed by persons with conditions in the autistic spectrum is emerging. Deficits in manipulating abstract meanings, translating principles across contexts, and attending to contextual meanings can be seen in lower and higher functioning individuals. Links between "executive function," "theory of mind," and findings from functional imaging are becoming apparent. There are consistent indications that frontal and temporal regions play a crucial role in these disorders. Associations with specific genetic defects has been suggested, but methods capable of discovering the complex interplay of several genes will be needed before generalized conclusions can be reached.

Autistic Disorder↗

PubMed1992

Goldenhar syndrome and autistic behaviour.

Two girls with concomitant Goldenhar syndrome (oculo-auriculovertebral spectrum disorder) and autistic disorder are described. One was diagnosed as having Goldenhar syndrome in the first few weeks of life and as having autistic disorder in her fifth year; the other was diagnosed as having Goldenhar syndrome when she was referred for evaluation of autistic symptoms at seven years of age. The type of physical abnormalities encountered in Goldenhar syndrome suggests damage to neural structures in the second or late stages of the first trimester. The two cases described in this report suggest that autistic disorder sometimes can result from neural damage during the second trimester.

Autistic Disorder↗

PubMed2003

Autism-related language, personality, and cognition in people with absolute pitch: results of a preliminary study.

Reports of a relatively high prevalence of absolute pitch (AP) in autistic disorder suggest that AP is associated with some of the distinctive cognitive and social characteristics seen in autism spectrum disorders. Accordingly we examined cognition, personality, social behavior, and language in 13 musicians with strictly defined AP (APS) and 33 musician controls (MC) without AP using standardized interviews and tests previously applied to identify the broad autism phenotype seen in the relatives of autistic probands. These included the Pragmatic Rating Scale (PRS) (social aspects of language) the Personality Assessment Schedule (PAS) (rigidity, aloofness, anxiety/worry, hypersensitivity), and WAIS performance subtests (PIQ). On the basis of their behavior in the interviews, subjects were classified as socially eccentric, somewhat eccentric, or not eccentric. Forty-six percent of the APS, but only 15% of the MC, were classified as socially eccentric (p < .03). APS but not MC showed higher scores on block design than on the other PIQ tests (p < .06), a PIQ pattern seen in autism spectrum disorders. Although APS and MC did not differ significantly on other measures it is of note that APS mean scores on the PRS and PAS (5.69, 4.92) were almost twice as high as those for the MC (3.03, 2.45). Thus, musicians with AP show some of the personality, language, and cognitive features associated with autism. Piecemeal information processing, of which AP is an extreme and rare example, is characteristic of autism and may be associated as well with subclinical variants in language and behavior. We speculate that the gene or genes that underlie AP may be among the genes that contribute to autism.

Adolescent↗

PubMed2006

Autism and developmental delay: a comparative clinical study in very young children using IBSE scale.

OBJECTIVE: This study improves the knowledge of early autistic symptomatology and research concerning (i) the significant differences in the behaviors of children with autistic disorder (AD) and children with a developmental delay (DD), and (ii) the influence of the cognitive delay on symptomatology. METHOD: Two groups of 20 young children (7-42 months) were compared: children with AD, and those with DD. The groups were paired by chronological and developmental age. The comparison was extended to four subgroups composed according to age (younger and older children--<24 months, >24 months) and to the global development quotient (GDQ) (the more and less delayed). Each child was evaluated with the Infant Behavior Summarized Evaluation scale (IBSE). RESULTS: For the younger AD children, significant differences affected social communication and their adaptation to the environment (intolerance to frustration, resistance to change). For the older children (>24 months), this study showed the rapid progression of the number of distinctive signs between AD and DD children according to age and/or developmental level. CONCLUSIONS: Cognitive delay has an important influence on the symptomatology at the moment of initial recognition of an autistic syndrome. This study is a complement for the fuller understanding of the nature and early diagnosis of disorders specific to autism at the earliest phases of development.

Autistic Disorder↗

PubMed2004

Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases.

OBJECTIVE: The aim of this study was to retrospectively review a large sample of children and adolescents with pervasive developmental disorders (PDDs) treated with open-label guanfacine in order to gather preliminary data as to its effectiveness and safety. METHOD: Eighty (80) subjects with PDDs (10 females, 70 males) (mean +/- SD age = 7.7 +/- 3.5 years, range 3-18 years) were treated with guanfacine within an academic specialty clinic. Charts were reviewed to determine the response of specific target symptoms, including hyperactivity, inattention, and impulsivity. The relationship between treatment response and age, diagnosis, level of cognitive impairment, and symptom severity was determined. Adverse effects were also evaluated. RESULTS: Guanfacine (mean daily dose = 2.6 +/- 1.7 mg, range 0.25-9 mg; mean duration of treatment = 334 +/- 374 days, range 7-1776 days) treatment was effective in 19 of 80 (23.8%) subjects. Subjects with PDD not otherwise specified (11 of 28 responders; 39.3%) and Asperger's disorder (2 of 6 responders; 33.3%) showed a greater rate of global response than those with autistic disorder (6 of 46 responders; 13.0 %). There was a trend for subjects without comorbid mental retardation (9 of 24 subjects; 37.5%) to respond at a greater rate than those with mental retardation (10 of 56 subjects; 17.9%). Symptom improvement was seen in hyperactivity, inattention, insomnia, and tics. Guanfacine was well tolerated, and did not lead to significant changes in blood pressure or heart rate. CONCLUSIONS: Guanfacine may have a role in the treatment of hyperactivity and inattention occurring in some persons with PDDs. Further studies are needed to determine its efficacy in this population.

Adolescent↗

PubMed2006

[Orientation of mental retardation from neurometabolic diseases].

INTRODUCTION AND DEVELOPMENT: Isolated mental retardation is rarely caused by metabolic factors. The application of a standardised protocol offers low diagnostic performance. There is no international agreement about what type of metabolic examination must be applied in patients with unspecific mental retardation. Nevertheless, and although they are infrequent, there are a number of inborn errors of metabolism that can present in this way. Urea cycle disorders, different forms of homocystinuria, creatine transport deficiency, 4-hydroxybutyric aciduria, Sanfilippo disease, adenylosuccinate lyase deficit and certain extraordinarily rare congenital disorders of the glycosylation of proteins are some examples of them. It is important first to consider those for which treatment is available and that could be diagnosed genetically for possible family counselling. CONCLUSIONS: Rather than applying a standardised study protocol it is essential is to perform a thorough appraisal of the signs and symptoms associated with the mental retardation (psychiatric disorders, autistic traits, predominant compromise of language, signs of cerebellar dysfunction, epilepsy, dysmorphic traits), since in most disorders it is necessary to apply specific analyses, which are not included in conventional metabolic studies and are only available in certain reference centres.

Algorithms↗

PubMed2004

Psychosocial issues in a child and adolescent psychiatric clinic population in Nigeria.

BACKGROUND: Psychosocial issues and interventions play a very important role in the aetiology, course and prognosis of several child psychiatric disorders. Psychosocial problems in a child and adolescent psychiatric clinic population in Nigeria were documented as a preliminary step towards the planning and development of this new facility. METHODS: A standardised assessment procedure was integrated into the routine at the clinic when services commenced. Psychosocial stressors and life events were measured using the interview method so that in-depth information could be obtained. RESULTS: Over the 3-year period of study, 79 (62.2%) of the 127 new referrals to the clinic had significant psychosocial stressors in the year preceding presentation. Problems with primary support, such as separation from parents to live with relatives, disruption of the family, abandonment by mother, psychiatric illness in a parent and sexual/physical abuse, occurred in 50 (39.4%) of the subjects. Problems with social environment occurred in 11 (8.7 %), 39 (30.7 %) had educational problems, 5 (3.9%) had economic problems and 15 (11.8%) of the children had "other" psychosocial stressors. Significantly more children and adolescents with disruptive behaviour disorders and disorders like enuresis, separation anxiety and suicidal behaviour had psychosocial stressors when compared to children with psychotic conditions, autistic disorder and epilepsy (chi(2) = 9.6; p = 0.048). CONCLUSIONS: The importance of the psychosocial diagnostic dimension in routine practice is illustrated in this study. Some psychosocial factors identified are cultural practices. The effects of these practices on child mental health require further study.

Adolescent↗

PubMed2003

Treatment of previously undiagnosed psychiatric disorders in persons with developmental disabilities decreased or eliminated self-injurious behavior.

BACKGROUND: Self-injurious behavior (SIB) is one of the most common challenging behaviors in persons with autistic disorder or severe/profound mental retardation. Many psychotropic drugs have been evaluated for their effectiveness in SIB. Results have varied, and no one psychotropic drug has been indicated for SIB. In this prospective, open clinical study, psychotropic drugs were used to treat the previously undiagnosed psychiatric disorder in persons exhibiting SIB. METHOD: Data were collected from 26 individuals with mental retardation (14 males, 12 females), 7 to 45 years of age (mean = 30.3 years), who exhibited SIB. Psychiatric diagnosis was made according to DSM-III-R and DSM-IV criteria. The Behavior Problem Inventory, Yudofsky's Overt Aggression Scale, repeated direct observation, and information on use of protective devices and Likert scales from log books were used to evaluate degree of SIB. Most of the patients were treated with different psychotropic drugs and behavior modification before they were evaluated for this study, but only 7 of them carried a psychiatric diagnosis. Data were collected between 1987 and 1997. RESULTS: Depressive disorders, impulse-control disorder, and anxiety disorder were the most common final diagnoses. Neuroleptics were discontinued in 5 patients and tapered by 50% to 75% in 14 patients. Antidepressants were added in 12 patients. Treatment of psychiatric disorders produced significant (p < .001) decrease in the severity of SIB in the 26 patients, and SIB was eliminated in 12 patients. The severity of SIB decreased to mild from a moderate, severe, or extreme degree in 11 patients and from an extreme to a severe degree in 3 patients. CONCLUSION: The most effective treatment for SIB that is resistant to environment changes and behavior modification in persons with developmental disabilities is the treatment of their psychiatric disorders with the appropriate psychotropics.

Adolescent↗

PubMed2006

Fragmented visuospatial processing in children with pervasive developmental disorder.

Children diagnosed with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Asperger Syndrome (AS) may be characterised by a similar perceptual focus on details as children with autistic disorder (AD). This was tested by analysing their performance in a visuoperceptual task [the Children's Embedded Figure Test (CEFT)] and a graphic reproduction task [the Rey Complex Figure Task (Rey CFT)]. Control groups were children with Tourette Syndrome (TS) and typically developing children. The TS sample performed similarly to the normal control group in both tasks. The CEFT results did not show the expected preference for local processing in children with PDD-NOS. However, the Rey CFT data revealed that the children with this lesser variant of PDD processed visuospatial information in a fragmented way and were deficient in global processing.

Asperger Syndrome↗

PubMed1998

Buspirone in the management of anxiety and irritability in children with pervasive developmental disorders: results of an open-label study.

BACKGROUND: We evaluated the efficacy and safety of buspirone in the management of anxiety and irritability in children with pervasive developmental disorders (PDD). METHOD: Twenty-two subjects, 6 to 17 years old, with DSM-III-R diagnosed PDD-NOS (N = 20) or autistic disorder (N = 2), were included. They were treated with buspirone in dosages ranging from 15 to 45 mg/day in an open-label trial lasting 6 to 8 weeks. Responders continued buspirone treatment and were followed up for up to 12 months. RESULTS: Nine subjects had a marked therapeutic response and 7 subjects a moderate response on the Clinical Global Impressions (CGI) scale after 6 to 8 weeks of treatment. Side effects were minimal, except for 1 patient who developed abnormal involuntary movements. CONCLUSION: These results suggest that buspirone may be useful for treating symptoms of anxiety and irritability in children with PDD.

Adolescent↗

PubMed2005

["Early" diagnosis and "early" intervention in children with mental retardation--when is early enough to diagnose them?].

Patients with mental retardation (MR) cannot always be diagnosed accurately by physicians who are specialized in child neurology and/or developmental disorders at their first visit to the clinic. Precise examination such as psychological tests and chromosomal analysis are often necessary to diagnose them. Some patients with autistic disorders without MR often are misdiagnosed as having MR. Patients with mild to moderate MR are sometimes diagnosed late in their late teens or twenties. Timely diagnosis and timely/continuous intervention is more important than early diagnosis and early intervention for the mentally retarded.

Adult↗