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PubMed2004

A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder.

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

Adolescent↗

PubMed2003

Dermatoglyphs of digito-palmar complex in autistic disorder: family analysis.

AIM: To examine the role of the genetic component in the quantitative dermatoglyphic traits of autistic patients and their families, and the transmission of the autism. METHODS: Finger and palm prints were taken from 120 autistic patients (92 males and 28 females), their parents (92 mothers and 70 fathers), 32 healthy brothers and 28 sisters, as well as 400 healthy controls (200 males and 200 females). An analysis of quantitative traits of dermatoglyphs on the fingers (FRC - finger ridge count) and palms (a-b, b-c, and c-d ridge count, and atd angle) was performed. Descriptive statistics, multivariate analysis of variance (MANOVA) with Tukey HSD post hoc test, and discriminant analysis were used to determine the differences among the groups. In addition, correlations among family members were analyzed. RESULTS: Multivariate analysis showed significant differences among examined groups of autistic patients and their family members and healthy volunteers regarding both group membership and sex. Autistic male patients differed significantly from the healthy controls in the ridge count (RC) on the fourth and fifth finger, and in a-b RC and atd angle of both hands. Healthy fathers of autistic patients differed in atd angle, and brothers of autistic patients differed in all palmar variables from the healthy control group. Mothers of autistic patients differed significantly from the healthy female controls in the RC of the first, fourth, and fifth finger, in a-b and c-d RC on the palms, and atd angle of both hands. The first two discriminant functions explained 85.4% of variance and separated groups clearly in two ways: the first function separated healthy controls from family members of autistic patients, and the second one males from females. Interfamilial analysis showed significant interclass correlations between autistic sons and their mothers or fathers in practically all variables. However, the correlation between parents and their autistic daughters was lower. Both mothers and fathers of autistic patients correlated with their healthy children only in palmar variables. CONCLUSIONS: We found significant differences in ridge counts on the fingers and palms between the affected patients and their healthy controls, but these differences also existed between family members of autistic patients and healthy controls. Particularly pronounced were the differences between healthy female controls and female family members, including not only autistic female patients, but also their healthy mothers and sisters. Since the mothers and their autistic sons showed higher statistically significant correlation in most of the examined variables, unlike the mothers and their autistic or healthy daughters, it is possible that there is a connection between a recessive X-chromosome linkage, as a genetic component in the etiology of autistic disorders, and the influence of the inactivation of the affected X-chromosome in the females.

Adolescent↗

PubMed1990

Using signal detection methodology to revise DSM-III-R: re-analysis of the DSM-III-R national field trials for autistic disorder.

Signal detection theory which takes into account the relative prevalence, sensitivity, and specificity of each of a set of criterion symptoms is used to determine an algorithm optimally predictive of a clinical diagnoses of autistic disorder using the data from the DSM-III-R national field trials. Findings support inclusion of one diagnostic criterion (marked lack of awareness of others) as mandatory, and four more (impaired imitation, abnormal social play, abnormal nonverbal communication, and abnormal speech) as alternate, associated criteria. Advantages of signal detection over other statistical methods for empirically deriving diagnostic standards are given, and implications for DSM-IV are discussed.

Algorithms↗

PubMed2001

De novo partial duplication of chromosome 7p in a male with autistic disorder.

We describe a de novo partial duplication of 7p in a 25-year-old male with autistic disorder (AD). High-resolution chromosome analysis revealed an extra segment added to the proximal short arm of chromosome 7. The G-band pattern was consistent with an inverted duplication of 7p11.2-p14.1. Fluorescent in situ hybridization (FISH), using a whole chromosome 7 DNA probe (Cytocell, Inc., UK), confirmed that the extra chromosome material is derived from chromosome 7, indicating that the patient is partially trisomic for a region of the short arm of chromosome 7. Partial duplication of the short arm of chromosome 7 is uncommon with little more than 30 cases in the literature. This is the first report of an individual with a 7p duplication who also has AD.

Adult↗

PubMed2004

Quetiapine in nine youths with autistic disorder.

OBJECTIVE: The aim of this study was to examine the effectiveness of quetiapine in adolescents suffering from autistic disorder (AD). METHODS: This was a 12-week, open-label study, for which medically healthy patients with AD between the ages of 10 and 17 years were eligible. Quetiapine treatment was gradually increased over the first 6 weeks of the study, to a total daily dose of 300 mg/day. Doses could then be increased to a maximum daily dose of 750 mg/day. Outcome measures included the Children's Psychiatric Rating Scale (CPRS) and the Clinical Global Impressions (CGI) scale. RESULTS: Nine (9) males were enrolled. Six (6) patients had previously been treated with other psychotropic agents. Although improvements in several symptom domains were observed on quetiapine, only 2 patients met a priori criteria for response ("much" or "very much improved" on the Clinical Global Impressions-Improvement Scale). In addition, only these same 2 patients' parents/guardians chose to continue quetiapine pharmacotherapy after study participation. CONCLUSIONS: These data suggest that quetiapine may not be a particularly effective agent in the treatment of adolescent patients with AD. However, should future studies be performed, it seems reasonable that they be conducted with more rigor, less treatment-resistant cohorts, and, possibly, a different dosing strategy.

Adolescent↗

PubMed1999

Gastrointestinal abnormalities in children with autistic disorder.

OBJECTIVES: Our aim was to evaluate the structure and function of the upper gastrointestinal tract in a group of patients with autism who had gastrointestinal symptoms. STUDY DESIGN: Thirty-six children (age: 5.7 +/- 2 years, mean +/- SD) with autistic disorder underwent upper gastrointestinal endoscopy with biopsies, intestinal and pancreatic enzyme analyses, and bacterial and fungal cultures. The most frequent gastrointestinal complaints were chronic diarrhea, gaseousness, and abdominal discomfort and distension. RESULTS: Histologic examination in these 36 children revealed grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15, and chronic duodenitis in 24. The number of Paneth's cells in the duodenal crypts was significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported in 21 children (58.3%), although there was no abnormality found in pancreatic function. Seventy-five percent of the autistic children (27/36) had an increased pancreatico-biliary fluid output after intravenous secretin administration. Nineteen of the 21 patients with diarrhea had significantly higher fluid output than those without diarrhea. CONCLUSIONS: Unrecognized gastrointestinal disorders, especially reflux esophagitis and disaccharide malabsorption, may contribute to the behavioral problems of the non-verbal autistic patients. The observed increase in pancreatico-biliary secretion after secretin infusion suggests an upregulation of secretin receptors in the pancreas and liver. Further studies are required to determine the possible association between the brain and gastrointestinal dysfunctions in children with autistic disorder.

Autistic Disorder↗

PubMed2004

High nitric oxide production in autistic disorder: a possible role for interferon-gamma.

BACKGROUND: Neuroimmune regulation abnormalities have been implicated in the pathophysiology of autistic disorder. Nitric oxide (NO) is involved in immune reactivity and is known to affect brain neurodevelopmental processes. Recent evidence indicates that NO, and cytokines involved in NO production, may be high in children with autism. The purpose of this study was to verify that plasma NO is high in children with autism and determine whether this elevation is related to plasma levels of cytokines involved in NO production. METHODS: The metabolites of NO, nitrite, and nitrate (NOx), along with the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and interleukin-1beta, were measured in plasma of 29 children with autism (mean age +/- SD = 6.1 +/- 2.8 years) and 27 age- and gender-matched healthy comparison subjects using commercially available assay kits. RESULTS: Plasma levels of NOx were significantly higher in the autistic subjects (p =.006); plasma levels of the cytokines did not differ between groups. NOx and IFN-gamma levels were positively correlated in the autistic subjects (r =.51; p =.005). CONCLUSIONS: These results confirm that plasma NO is high in some children with autism and suggest that this elevation may be related to IFN-gamma activity.

Autistic Disorder↗

PubMed2003

Risk factors for self-injurious behaviours among 222 young children with autistic disorders.

The aim of this study was to identify risk factors for self-injurious behaviours (SIBs) in children with autistic disorders. The occurrence of SIB was examined in comparison with the following variables: chronological age, sex, adaptive skills, speech level, associated medical condition, degree of autism and parental social class. The subjects were 222 children aged under 7 years and all of them fulfilled the ICD-10 criteria for infantile autism. Retrospective data were collected on demographic characteristics and medical condition. Children were assessed in terms of speech, degree of autism and adaptive skills in communication, socialization and daily living skills domains. Results indicated that 50% of the children experienced SIB and 14.6% had severe SIBs. Lower chronological age, associated perinatal condition, a higher degree of autism and a higher daily living skills delay were risk factors of SIBs but parental class, sex and epilepsy were not.

Activities of Daily Living↗

PubMedDate not supplied

[Neuropsychological data about children with autistic disorder and an intellectual development within what is considered to be a normal span of time].

INTRODUCTION: Characteristic symptoms of autistic disorder (AD) can be the result of cognitive impairment which can be produced by specific neurological irregularities. Up until now a specific cognitive deficit in autism has not been found, although the majority of people with autism show intellectual impairment, verbal scores lower than manipulative measures and executive dysfunctions. AIMS: A neuropsychological evaluation of children with AD was planned. These children had intellectual abilities in the normal range. They were compared with two other groups, one with pervasive developmental disorder not otherwise specified (PDD-NS), and the other from the general population. SUBJECTS AND METHODS: A battery of neuropsychological tests was carried out on five boys AD, five boys PDD-NS, and five boys of the general population. All of them were between 9 and 15 years old and their intellectual abilities were within the normal range. RESULTS: The children AD obtained verbal scores lower than their visual-perception scores. They also showed good dynamic coordination of movement. Scores in episodic memory tasks where executive strategies are needed were low. CONCLUSION: The characteristics described in the paper do not demonstrate a specific profile of the AD, but they can be useful in diagnoses and in planning treatment.

Adolescent↗

PubMed2005

Examining the relationship between executive functions and restricted, repetitive symptoms of Autistic Disorder.

The executive function theory was utilized to examine the relationship between cognitive process and the restricted, repetitive symptoms of Autistic Disorder (AD). Seventeen adults with AD were compared to 17 nonautistic controls on a new executive function battery (Delis-Kaplin Executive Function Scales). Restricted, repetitive symptoms were measured by a variety of instruments (i.e., the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, Gilliam Autism Rating Scale, and the Aberrant Behavior Checklist). The study replicated the executive function profile that has been reported in adults with AD. In addition to the replication findings, the study found several executive processes (i.e., cognitive flexibility, working memory, and response inhibition) were highly related to the restrictive, repetitive symptoms of AD; whereas, other executive process (i.e., planning and fluency) were not found to be significantly correlated with restricted, repetitive symptoms. Similarly, we found an executive function model consisting of relative strengths and deficits was the best predictor of restricted, repetitive symptoms of autism. The implications for the executive function theory and how the theory predicts core symptoms of autism are discussed.

Adolescent↗

PubMed1999

Genetic studies of autistic disorder and chromosome 7.

Genome-wide scans have suggested that a locus on 7q is involved in the etiology of autistic disorder (AD). We have identified an AD family in which three sibs inherited from their mother a paracentric inversion in the chromosome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs have AD, while the female sib has expressive language disorder. The mother carries the inversion, but does not express AD. Haplotype data on the family suggest that the chromosomal origin of the inversion was from the children's maternal grandfather. Based on these data, we have genotyped 76 multiplex (>/=2 AD affecteds/family) families for markers in this region of 7q. Two-point linkage analysis yielded a maximum heterogeneity lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoint MLS and NPL analyses resulted in peak scores of 1.77 at D7S2527 and 2.01 at D7S640. Examination of affected sibpairs revealed significant paternal (P = 0.007), but not maternal (P = 0. 75), identity-by-descent sharing at D7S640. Significant linkage disequilibrium was detected with paternal (P = 0.02), but not maternal (P = 0.15), transmissions at D7S1824 in multiplex and singleton families. There was also evidence for an increase in recombination in the region (D7S1817 to D7S1824) in the AD families versus non-AD families (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results provide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expressed.

Adult↗

PubMed2006

Self, other and dialogical space in autistic disorders.

The authors propose to re-evaluate Tustin's thesis using both the extensive clinical material of a child with an autistic disorder [PDD], and current research on infant development. Beebe's concept of 'interaction structure' that could be inferred from the fifth month of life using face-to-face research data is used for postulating a dialogic space that would be generated inside such structure, allowing for definition of self and other in a relationship. If such space is collapsed, the other would be a threat of annihilation for the self, thus it should be avoided or merged with, which could explain the systematic avoidance of the not-me in autistic states. The authors stress that these ideas are just one alternate model, among several, that seems to be able to explain the patient's deviant development.

Autistic Disorder↗

PubMed2004

[Anatomical and functional abnormalities of central nervous system in autistic disorder: a MRI and SPECT study].

We present a study of anatomical and functional abnormalities of central nervous system (CNS) from patients with autistic disorder (AD); magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were used for the investigation. The population studied was composed of 24 patients, 15 (62.5%) males and 9 (17.5%) females, mean age 9 years. MRI was performed in all patients and SPECT was performed in 19 patients; 75% (n=18) of patients had anatomical abnormalities and all patients that realized SPECT had functional abnormalities. Anatomical abnormalities were preferentially noted in corpus callosum (25%), septum pellucidum (15.63%), cerebral ventricles (12.55%), cerebellum (9.38%), temporal lobes (6.25%), occipital lobes (6.25%) and hippocampus (6.25%). Functional abnormalities predominated in frontal lobes (53.13%), temporal lobes (28.13%), parietal lobes (15.63%) and basal ganglia (3.13%). However, anatomical and functional abnormalities of CNS are not priorities for diagnosis, which should have always clinical validation.

Adolescent↗

PubMed2005

Tetrahydrobiopterin in the treatment of children with autistic disorder: a double-blind placebo-controlled crossover study.

Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.

Autistic Disorder↗

PubMed2000

Female with autistic disorder and monosomy X (Turner syndrome): parent-of-origin effect of the X chromosome.

We have ascertained and examined a patient with autistic disorder (AD) and monosomy X (Turner syndrome). The patient met Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)/International Classification of Diseases (ICD-10) criteria for AD verified by the Autism Diagnostic Interview-Revised. The patient exhibited both social and verbal deficits and manifested the classical physical features associated with monosomy X. Skuse et al. [1997: Nature 387:705-708] reported three such cases of AD and monosomy X in their study of Turner syndrome and social cognition. They observed that monosomy X females with a maternally inherited X chromosome had reduced social cognition when compared with monosomy X females with a paternally inherited X chromosome. All three cases of AD and monosomy X were maternally inherited. Based on their data, they suggested that there was a gene for social cognition on the X chromosome that is imprinted and not expressed when the X chromosome is of maternal origin. Thus, we conducted parent-of-origin studies in our AD/monosomy X patient by genotyping X chromosome markers in the patient and her family. We found that the patient's X chromosome was of maternal origin. These findings represent the fourth documented case of maternal inheritance of AD and monosomy X and provide further support for the hypothesis that parent-of-origin of the X chromosome influences social cognition.

Adult↗

PubMed1994

Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation.

In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.

Autistic Disorder↗

PubMed2000

Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

Adolescent↗

PubMedDate not supplied

Accentuated Virchow-Robin spaces in the centrum semiovale in children with autistic disorder.

OBJECTIVE: The purpose of this study was to assess the incidence of abnormal Virchow-Robin (VR) spaces in children and adolescents with an autistic disorder (AD). An increased incidence of enlarged VR spaces in children has been reported in several developmental disorders. METHODS: Sixteen children and adolescents (13 male, 3 female; mean age = 143.5 months; mean IQ = 95.1) with an AD, verified by use of standardized procedures (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule-Revised), received cranial magnetic resonance (MR) imaging. Sixteen children and adolescents (13 male, 3 female; mean age = 160.7 months; mean IQ = 111.6) without AD, as determined using the same procedures, were scanned as a comparison group. The MR scans were performed using a 1.5-T scanner. Two T1-weighted spoiled GRASS sequences (0.7-mm coronal thin-slice, 0-mm gap; 1.5-mm sagittal, 0-mm gap) and a complementary T2-weighted fast spin echo sequence (1.5-mm, 0-mm gap) were obtained. A neuroradiologist and a neurobiologist without clinical information determined the incidence of normal, accentuated, and/or dilated VR spaces. RESULTS: Seven of 16 subjects with AD (approximately 44%) had dilated VR spaces in the centrum semiovale. No grossly abnormal spaces were present in the control subjects. CONCLUSION: Unusually large VR spaces are seen in at most 22% to 27% of MR scans in children with tension headaches and other psychiatric disorders, suggesting that the incidence of spaces of this type is greater in AD than in other abnormal populations. The origin and significance of this phenomenon remain unknown.

Adolescent↗