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Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease.

This is a cross-sectional study that compares lifetime prevalence of gastrointestinal (GI) symptoms in children with autistic spectrum disorders (ASDs) and children with typical development and with other developmental disabilities (DDs) and examines the association of GI symptoms with a family history of autoimmune disease. A structured interview was performed in 50 children with ASD and 2 control groups matched for age, sex, and ethnicity-50 with typical development and 50 with other DDs. Seventy-four percent were boys with a mean age of 7.6 years (SD, +/-3.6). A history of GI symptoms was elicited in 70% of children with ASD compared with 28% of children with typical development (p <.001) and 42% of children with DD (p =.03). Abnormal stool pattern was more common in children with ASD (18%) than controls (typical development: 4%, p =.039; DD: 2%, p =.021). Food selectivity was also higher in children with ASD (60%) compared with those with typical development (22%, p =.001) and DD (36%, p =.023). Family history of autoimmune disease was reported in 38% of the ASD group and 34% of controls and was not associated with a differential rate of GI symptoms. In the multivariate analysis, autism (adjusted odds ratio (OR), 3.8; 95% confidence interval (CI), 1.7-11.2) and food selectivity (adjusted OR, 4.1; 95% CI, 1.8-9.1) were associated with GI symptoms. Children with ASD have a higher rate of GI symptoms than children with either typical development or other DDs. In this study, there was no association between a family history of autoimmune disease and GI symptoms in children with ASD.

Adolescent↗

Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports.

Although autistic-like behaviors were described even in the earliest reports of fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and autism were reported as a dual diagnosis in six school-aged children. The purpose of the present series of case reports is to describe marked autistic characteristics in three much younger children (25-36 months) with histories of prenatal exposure to alcohol and other drugs. The behavioral characteristics of these children are described and compared with current diagnostic criteria for autistic disorder. In addition, longitudinal scores on the Bayley Scales of Infant Development are provided to underscore the marked developmental delays shown by each of the children. Limitations of these case reports are discussed with suggestions for future prospective research.

Autistic Disorder↗

Treatment of obsessive-compulsive spectrum disorders with SSRIs.

BACKGROUND: Obsessive-compulsive spectrum disorders (OCSDs) are now recognised as distinct diagnostic entities related to obsessive-compulsive disorder (OCD). The features of OCSDs and OCD overlap in many respects including demographics, repetitive intrusive thoughts or behaviours, comorbidity, aetiology and preferential response to anti-obsessional drugs such as the selective serotonin reuptake inhibitors (SSRIs). METHOD: Literature was reviewed and preliminary data from various studies were re-examined to assess the relationship between compulsivity and impulsivity, and between OCD and OCSDs. RESULTS: OCSDs include both compulsive and impulsive disorders and these can be viewed as lying at opposite ends of the dimension of risk avoidance. Compulsiveness is associated with increased frontal lobe activity and increased serotonergic activity, while impulsiveness is associated with reduced activity of these variables. Neural circuits affected by serotonergic pathways have been identified and pharmacological challenge of OCSD patients with serotonin receptor agonists have supported the involvement of serotonergic processes. CONCLUSIONS: SSRIs such as fluvoxamine have established efficacy in OCD and preliminary studies indicate that they are also effective in OCSDs. The features of three specimen OCSDs--body dysmorphic disorder, pathological gambling and autism--and their treatment with SSRIs are reviewed.

Autistic Disorder↗

The autism-spectrum quotient (AQ) children's version in Japan: a cross-cultural comparison.

In the current study, the child AQ was administered in Japan, to examine whether the UK results for reliability and validity generalize to a different culture. Assessment groups were: Group 1: n = 81 children with Asperger Syndrome (AS) or high-functioning autism (HFA); Group 2: n = 22 children diagnosed PDD-NOS with average IQ; and Group 3: n = 372 randomly selected controls from primary and secondary schools. Both clinical groups scored significantly higher than controls (AS/HFA mean AQ = 31.9, SD = 6.93; PDD-NOS mean AQ = 28.0, SD = 6.88; controls mean AQ = 11.7, SD = 5.94). Among the controls, males scored significantly higher than females. The pattern of difference between clinical groups and controls was found to be similar in both countries.

Adolescent↗

Prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio.

To date, there have been few surveys of psychotropic and antiepileptic drug (AED) prevalence in individuals with autism-spectrum conditions. We surveyed 747 families in the Autism Society of Ohio regarding the use of psychotropic drugs, AEDs, and over-the-counter (OTC) preparations for autism. In all, 417 families (55.8%) replied. A total of 45.6% were taking some form of psychotropic agent (including St. John's wort and melatonin), whereas 11.5% were taking AEDs, and 10.3% took OTC autism preparations. The most common psychotropic agents included antidepressants (21.6%), antipsychotics (14.9%), antihypertensives (12.5%), and stimulants (11.3%). Some 51.6% were prescribed psychotropic drugs or AEDs, and 55.4% took psychotropic drugs, AEDs, or autism supplements. Demographic variables frequently found to be associated with medication use included greater age, more severe autism, more severe intellectual handicap, and housing outside the family home. Whereas there is empirical support for the use of some of these psychotropic agents in autism, others are being prescribed with minimal research support. OTC autism preparations were used in substantial numbers of individuals, despite limited research support and the possibility of toxic effects.

Adolescent↗

Autism: a window onto the development of the social and the analytic brain.

Although the neurobiological understanding of autism has been increasing exponentially, the diagnosis of autism spectrum conditions still rests entirely on behavioral criteria. Autism is therefore most productively approached using a combination of biological and psychological theory. The triad of behavioral abnormalities in social function, communication, and restricted and repetitive behaviors and interests can be explained psychologically by an impaired capacity for empathizing, or modeling the mental states governing the behavior of people, along with a superior capacity for systemizing, or inferring the rules governing the behavior of objects. This empathizing-systemizing theory explains other psychological models such as impairments of executive function or central coherence, and may have a neurobiological basis in abnormally low activity of brain regions subserving social cognition, along with abnormally high activity of regions subserving lower-level, perceptual processing--a pattern that may result from a skewed balance of local versus long-range functional connectivity.

Attention↗

Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.

Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800-1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits. Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function.

Adolescent↗

The autistic brain: birth through adulthood.

PURPOSE OF REVIEW: We discuss evidence of brain maldevelopment in the first years of life in autism and new neuroanatomical and functional evidence from later ages of development. RECENT FINDINGS: Head circumference, an accurate indicator of brain size in children, was reported to jump from normal or below normal size in the first postnatal months in autistic infants to the 84 th percentile by about 1 year of age; this abnormally accelerated growth was concluded by 2 years of age. Infants with extreme head (and therefore brain) growth fell into the severe end of the clinical spectrum and had more extreme neuroanatomical abnormalities. In the frontal and temporal lobes in autism, there have been reports of abnormal increases in gray and white matter at 2 to 4 years; reduced metabolic measures; deviant diffusion tensor imaging results in white matter; underdeveloped cortical minicolumns; and reduced functional activation during socio-emotional, cognitive and attention tasks. Cerebellar abnormalities included abnormal volumes, reduced number and size of Purkinje neurons in the vermis and hemispheres, molecular defects, and reduced functional activation in posterior regions. SUMMARY: A new neurobiological phenomenon in autism has been described that precedes the onset of clinical behavioral symptoms, and is brief and age-delimited to the first two years of life. The neurobiological defects that precede, trigger, and underlie it may form part of the developmental precursors of some of the anatomical, functional, and behavioral manifestations of autism. Future studies of the first years of life may help elucidate the factors and processes that bring about the unfolding of autistic behavior.

Autistic Disorder↗

New perspectives in autism, Part II: The differential diagnosis and neurobiology of autism.

The clinical spectrum of autism spans a broad range of functions, but the core symptoms remain the same regardless of the intelligence of the child: the autistic type of social deficit that ranges from a lack of inclination to relate to extreme difficulty with the mechanics of social interactions, a global communication deficit that involves both verbal and nonverbal modes, and a severe cognitive deficit involving concept formation (abstraction) that is combined with an exceptional memory for factual information. These symptoms may vary dramatically in severity, but the basic deficits are identifiable regardless of IQ. Under-recognition of autism is a major problem at all IQs, but especially in patients with IQs above 50. No drugs have been found to significantly improve the core deficits in autism. Antipsychotics should be avoided except for short-term use. Antidepressants, anxiolytics, and anticonvulsants are important in the treatment of depression, affective modulation, situation-related stress, and seizures. Intensive social skills training is assuming a prominent role in behavior modification programs, and success with higher-functioning autistic children suggests that outcome can be improved by intensive training. The neurobiology of autism has also undergone dramatic changes. The psychogenic theories of etiology have been completely invalidated. Autism is now considered to be a neurological disorder resulting from an error in brain development. The precise location and nature of this deficit are still being actively debated and investigated. One theory emphasizes a dysfunction of the limbic system that results in an impairment in the acquisition of information. A second theory proposes a primary role for dysfunction of the cortical association network responsible for the processing of information.

Autistic Disorder↗

A comparison of the effects of parental risk markers on pre- and perinatal variables in multiple patient cohorts with fetal alcohol syndrome, autism, Tourette syndrome, and sudden infant death syndrome: an enviromic analysis.

The prevalence and magnitude of effect of individual risk markers for specific developmental disorders vary widely across diagnostic category. The four study cohorts for this project were patients from four diagnostic registries in North Dakota for fetal alcohol syndrome (FAS), autism, sudden infant death syndrome (SIDS), and Tourette syndrome. These four cohorts were used to estimate prevalence and magnitude of effect of parental risk markers in patients with developmental disabilities. Cases with North Dakota birth certificates were matched with controls. Using birth certificate data, we then examined five parental risk markers for each cohort and estimated direct and indirect effects for each risk marker by cohort. The authors found two significant paternal risk markers (age in SIDS and education in FAS). Significant maternal markers were age in SIDS, education in FAS, autism, and SIDS. Marital status was a significant risk marker in FAS. Effect sizes were estimated using paired t tests, odds ratios, and population attributable risk (PAR) for both direct and indirect effects for each marker. We estimated both direct and indirect effects to allow for direct comparisons of the differential effect estimates of each of these markers. The direct effect of parental markers differs across diagnostic cohorts of patients. Use of cohorts from similar denominator populations obtained from prevalence studies is a useful methodological tool for estimating the prevalence and magnitude of effect of risk markers.

Age Factors↗

Sulphation deficit in "low-functioning" autistic children: a pilot study.

BACKGROUND: Parents of autistic children and autism support groups often report that autistic episodes are exacerbated when the children eat certain foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples, and bananas. The hypothesis that autistic behavior might be related to metabolic dysfunctions has led us to investigate in a group of "low functioning" autistic children and in an age-matched control group each made up of 20 subjects, the sulphation capacity available. METHODS: Utilizing the biochemical characteristics of paracetamol we evaluated by high performance liquid chromatography, the urine paracetamol-sulfate/paracetamol-glucuronide (PS/PG) ratio in all subjects following administration of this drug. RESULTS: The PS/PG ratio in the group of autistic subjects gave a significantly lower results than the control group with p < .00002. CONCLUSIONS: The inability to effectively metabolize certain compounds particularly phenolic amines, toxic for the CNS, could exacerbate the wide spectrum of autistic behavior.

Acetaminophen↗

'Obsessions' in children with autism or Asperger syndrome. Content analysis in terms of core domains of cognition.

BACKGROUND: We report a survey of the content of obsessions in children with autism spectrum conditions. We use the term 'obsessions' narrowly, to indicate strong, repetitive interests. We predicted that obsessions would not cluster randomly, but rather would occur significantly more often in the domain of 'folk physics' (an interest in how things work), and significantly less often in the domain of 'folk psychology' (an interest in how people work). These predictions were tested relative to a control group of 33 children with Tourette syndrome. AIMS: To examine the content of autistic obsessions, and to test the theory that these reflect an evolved cognitive style of good folk physics alongside impaired folk psychology. METHOD: Ninety-two parents returned a questionnaire designed to determine the subject of their child's obsessional interests. The results were analysed in terms of core domains of cognition. RESULTS: Both predictions were confirmed. CONCLUSIONS: These results suggest that impaired folk psychology and superior folk physics are part of the cognitive phenotype of autism. A content-free theory of obsessions is inadequate.

Asperger Syndrome↗

[Nocturnal polysomnogram in childhood autism without epilepsy].

AIMS: To evaluate the presence of epileptiform discharges and the organisation of nocturnal sleep of autistic children without nocturnal polysomnographic epileptic seizures. SUBJECTS AND METHODS: Cross section analysis. SUBJECTS: 21 boys and girls with autistic spectrum using DSM IV criteria between the ages of 4 and 12, compared with a control group made up of normal children of the same ages. METHODS: nocturnal polysomnogram with a minimum efficiency of 75%. ANALYSIS: t test to compare the cycles and phases of sleep with significance p< 0.05. RESULTS: SUBJECTS presented a maximum of four sleep cycles compared with five or six in the control subjects. From the first third of the night onwards there was an increase in the slowest phases. 66% presented epileptiform paroxysmal discharges, all of which originated in the anterior half of the brain. CONCLUSION: Sleep is not destructured, but it is reduced in length, with epileptiform paroxysms of predominantly frontal origin. This could indicate that these two parameters are intrinsic to the autistic spectrum, as well as indicating a more focused origin of the generalised picture which is possibly closely related with the qualitative alteration of the social experiences of these children.

Autistic Disorder↗

[The Autism-Spectrum Quotient (AQ) Japanese version: evidence from high-functioning clinical group and normal adults].

Baron-Cohen, Wheelwright, Skinner, Martin, and Clubley (2001) constructed brief, self-administered instruments named the Autism-Spectrum Quotient (AQ), for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum. In this paper, we report on a Japanese version of this new instrument. Three groups of Japanese subjects were assessed. Group 1 (n = 57) consisted of adults with Asperger Syndrome (AS) or high-functioning autism (HFA). The other two groups were control groups. Subjects of Group 2 (n = 194) were normal adults and those of Group 3 (n = 1 050) were students selected from five Universities in Tokyo and Chiba. The adults with AS/HFA had a mean AQ score of 37.9 (SD = 5.31), which was significantly higher than the two control groups (Group 2: X = 18.5, SD = 6.21, and Group 3: X = 20.7, SD = 6.38). While eighty-eight percent of the adults with AS/HFA scored more than 33 points, only 3% of subjects in the two control groups indicated those points. Among the controls, males scored slightly but significantly higher than females. The reliability of the AQ in both test-retest and inter-rater measures were significantly high.

Adult↗

Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL.

An Australian patient with autism was found to be heterozygous for two mutations in the gene encoding adenylosuccinate lyase (ASL), resulting in the protein mutations E80D and D87E. The patient's mother carried only the E80D mutation. The equivalent positions are 62 and 69 in Bacillus subtilis ASL. Although both human and B. subtilis enzymes normally have Asp at position 87 (or 69), the B. subtilis ASL has Ile and Asp at 62 and 65, respectively, whereas human ASL has Glu and Arg at the equivalent positions. We have constructed, expressed, and purified the double mutant I62E/D65R as a "humanized" normal B. subtilis enzyme to compare with enzymes with a single mutation at position 62 (I62D/D65R), at position 69 (I62E/D65R/D69E), or at both positions (I62D/D65R/D69E). V(max) for conversion of adenylosuccinate to AMP and fumarate is 0.57 micromol/min/mg for I62E/D65R, 0.064 micromol/min/mg for I62D/D65R, 0.27 micromol/min/mg for I62E/D65R/D69E, and 0.069 micromol/min/mg for I62D/D65R/D69E. The K(m) for adenylosuccinate is elevated in the X62D mutants, and I62D/D65R is the least stable of these ASLs at 37 degrees C. The CD spectra of mutant and wild type enzymes are similar; thus, there are no appreciable structural changes. Clearly the Asp(62) causes the most drastic effect on ASL function, whereas the Glu(69) mutation produces only modest change. These results emphasize the importance of expanding tests for ASL deficiency to individuals with developmental delay of any severity, including individuals with autistic spectrum disorder. This study further demonstrates the usefulness of the B. subtilis ASL as a model to mimic the defective enzyme in ASL deficiency.

Adenosine Monophosphate↗

Probiotics as an adjuvant to detoxification protocols.

Autism is a developmental disease characterized by a spectrum of symptoms ranging from decreased verbal skills and social withdrawal, to repetitive behavior and violent outbursts. Genetic analysis has yielded a few potentially interesting genes, however no clear linkage has been established. For this reason, it has been suggested that the etiology of autism may involve multiple loci. This, in large part, explains why so many different theories abound. One such theory is that of mercury poisoning. Environmentally acquired mercury, either through some causal contact or through vaccination, has been postulated as the culprit. Mercury is thought to be exerting its neurological effect on the brain. The standard treatment has been to apply chelating agents in an attempt to extricate the mercury. One missing component in the treatment is the utilization of the body's own detoxification mechanisms. Arguably the largest detoxification component of the body, the endogenous enteric bacteria are an enormous reservoir, which can be constantly and safely replenished. This paper discusses the use of high-dose probiotics as an adjuvant for detoxification protocols with an emphasis on use in autistics.

Autistic Disorder↗

Understanding atypical emotions among children with autism.

Children with autism are said to be poor mind readers: They have a limited understanding of the role that mental states play in determining emotions and behavior. In this research, 23 high-functioning children from the autistic spectrum (M age 9 years 3 months), 42 6-year-old controls, and 43 10-year-old controls were presented with six emotion-evoking stories and they were asked to explain protagonists' typical and atypical emotions. In the case of typical emotions, as expected on the basis of the mindblind hypothesis, children from the autistic spectrum gave few mental state explanations, referring to fewer than even the 6-year-old control group. However, in the case of atypical emotions, the autistic group performed as well as the 10-year-old controls. Their explanations for the atypical emotions demonstrate that children from the autistic spectrum indeed have the capacity to mind read (with respect to both desires and beliefs), although they do not always use this capacity in the same way as normally developing children. It is argued that the mind-reading capacity of high-functioning children from the autistic spectrum might be basically intact; unused in everyday circumstances but not necessarily defective.

Affect↗

Neuropsychological assessment of a group of UK patients with Cohen syndrome.

Cohen syndrome is a rare autosomal recessive syndrome with a distinctive clinical phenotype that includes mental retardation and a characteristic sociable disposition. Variability in the level of learning disability and the behavioural phenotype is seen in the published literature. In a cohort of Finnish Cohen syndrome patients, severe mental retardation and non-maladaptive behaviour were described. Outside of Finland, autistic-spectrum behaviour has been reported in a few isolated Cohen syndrome patients but in a recent UK study was found to be highly prevalent. We report the results of neuropsychological studies in a group of 16 genetically heterogeneous patients, all with the characteristic clinical features of Cohen syndrome. Of the 9 patients who underwent formal neuropsychological testing, all but one was functioning in the severely mentally impaired range. Of the remaining patients, 3 were below the age of formal testing and 4 had such profound learning and behavioural problems that they were deemed unable to participate in testing. Mild maladaptive behaviour was observed in 13 patients and 3 were documented as having significant maladaptive behaviour. In contrast to the Finnish group of Cohen syndrome patients, this UK study identifies significant neuropsychological impairment combined with maladaptive behaviour as a characteristic of Cohen syndrome. Although autistic-type behaviour was observed, an increased prevalence of autism in Cohen syndrome was not confirmed.

Adolescent↗