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PubMed1999

Is schizophrenia a risk factor for epilepsy or acute symptomatic seizures?

PURPOSE: The precise prevalence of epilepsies and seizures in patients with schizophrenia remains unclear. METHODS: To assess the prevalence of epilepsy and of acute symptomatic seizures in schizophrenics, we conducted a survey in a urban sector of Marseilles that includes 56,910 inhabitants, among whom 1,154 had been treated for psychiatric disorders, including 460 for schizophrenia or paranoid disorder (PD) (DSM III-R 295 and 297.1, respectively; mean age, 41.9 years; range, 17-79 years; 215 men and 245 women). RESULTS: All 460 patients were receiving long-term neuroleptic drug therapy, and 397 had been hospitalized at least once in the past year, whereas 63 were followed up as outpatients only. Seizures were present in the history of 12 patients: five had various forms of chronic epilepsy (four men, one woman; DSM III-R 295.1, one case; 295.3, two cases; 295.9, two cases), and three of these experienced seizures only after the onset of their psychiatric condition; five had acute symptomatic seizures (four men, one woman; 295.1, two cases; 295.3, 295.9, and 297.1, one case), and two had only pseudoepileptic events (both 295.3). CONCLUSIONS: This survey shows that the prevalence of epilepsy and acute symptomatic seizures is comparatively low in patients with schizophrenia or PD (10.8 per thousand each, respectively), and that the prevalence of a history of seizures (21.7 per thousand in this study) is not particularly increased in this middle-aged population. In contrast to childhood-onset autistic disorders, schizophrenia or PD are not major risk factors for epilepsy or acute symptomatic epileptic seizures.

Acute Disease↗

PubMed2006

Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation.

OBJECTIVE: Autism is a complex, largely genetic psychiatric disorder. In the majority of cases, the cause of autism is not known, but there is strong evidence for a genetic etiology. To identify candidate genes, the physical mapping of balanced chromosomal aberrations is a powerful strategy, since several genes have been characterized in numerous disorders. In this study, the authors analyzed a balanced reciprocal translocation arising de novo in a subject with autism and mental retardation. METHOD: The authors performed the physical mapping of the balanced 9q23/10q22 translocation by fluorescent in situ hybridization experiments using bacterial artificial chromosome clones covering the areas of interest. RESULTS: Findings revealed that the KCNMA1 gene, which encodes the alpha-subunit of the large conductance Ca(2+)-activated K(+) (BK(Ca)) channel, a synaptic regulator of neuronal excitability, is physically disrupted. Further molecular and functional analyses showed the haploinsufficiency of this gene as well as decreased activity of the coded BK(Ca )channel. This activity can be enhanced in vitro by addition of a BK(Ca )channel opener (BMS-204352). Further mutational analyses on 116 autistic subjects led to the identification of an amino acid substitution located in a highly conserved domain of the protein not found in comparison subjects. CONCLUSIONS: These results suggest a possible association between a functional defect of the BK(Ca) channel and autistic disorder and raise the hypothesis that deficits in synaptic transmission may contribute to the physiopathology of autism and mental deficiency.

Autistic Disorder↗

PubMed2004

Polymorphisms in xenobiotic metabolism genes and autism.

Autism is a neurodevelopmental syndrome defined by deficits in social reciprocity and communication and by unusual repetitive behaviors. Although there is an underlying genetic predisposition, the etiology of autism is currently unknown. A recent increase in prevalence suggests that genetically determined vulnerability to environmental exposure might contribute to the causation of autism. We performed family-based association studies of polymorphisms in metal-regulatory transcription factor 1(MTF1), a multispecific organic anion transporter (ABCC1), proton-coupled divalent metal ion transporters (SLC11A3 and SLC11A2), paraoxonase 1 (PON1), and glutathione S-transferase (GSTP1) genes in 196 autistic disorder families. There was deviation from the expected pattern of transmission for polymorphisms in MTF1 (Single nucleotide polymorphism database reference identification number, dbSNP rs3790625, P = .02) and divalent metal ion transporter SLC11A3 (dbSNP rs2304704, P = .07) genes. Although these results might represent chance finding, further investigations of genetic variations of metal metabolism in autism are warranted.

Autistic Disorder↗

PubMed2003

Brief report: pitocin induction in autistic and nonautistic individuals.

Oxytocin plays an important role in social-affiliative behaviors. It has been proposed that exposure to high levels of exogenous oxytocin at birth, via pitocin induction of delivery, might increase susceptibility to autism by causing a downregulation of oxytocin receptors in the developing brain. This study examined the rates of labor induction using pitocin in children with autism and matched controls with either typical development or mental retardation. Birth histories of 41 boys meeting the criteria for autistic disorder were compared to 25 age- and IQ-matched boys without autism (15 typically developing and 10 with mental retardation). There were no differences in pitocin induction rates as a function of either diagnostic group (autism vs. control) or IQ level (average vs. subaverage range), failing to support an association between exogenous exposure to oxytocin and neurodevelopmental abnormalities.

Adolescent↗

PubMed2002

Vaccines, viruses, and voodoo.

Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease.

Adolescent↗

PubMed1994

Autism in thalidomide embryopathy: a population study.

Of a population of 100 Swedish thalidomide embryopathy cases, at least four met full criteria for DSM-III-R autistic disorder and ICD-10 childhood autism. Thalidomide embryopathy of the kind encountered in these cases affects fetal development early in pregnancy, probably on days 20 to 24 after conception. It is argued that the possible association of thalidomide embryopathy with autism may shed some light on the issue of which neural circuitries may be involved in autism pathogenesis.

Adult↗

PubMed1995

Adenylosuccinate lyase (ADSL) and infantile autism: absence of previously reported point mutation.

Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine-to-proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR-amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM-III-R criteria for autistic disorder. None of the 119 patients tested were found to have this mutation. Furthermore, on preliminary screening using singlestrand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism.

Adenylosuccinate Lyase↗

PubMed2005

Evaluating the effectiveness of teacher training in Applied Behaviour Analysis.

Interventions for children with autism based upon Applied Behaviour Analysis (ABA) has been repeatedly shown to be related both to educational gains and to reductions in challenging behaviours. However, to date, comprehensive training in ABA for teachers and others have been limited. Over 7 months, 11 teachers undertook 90 hours of classroom instruction and supervision in ABA. Each teacher conducted a comprehensive functional assessment and designed a behaviour support plan targeting one behaviour for one child with an autistic disorder. Target behaviours included aggression, non-compliance and specific educational skills. Teachers recorded observational data for the target behaviour for both baseline and intervention sessions. Support plans produced an average 80 percent change in frequency of occurrence of target behaviours. Questionnaires completed by parents and teachers at the end of the course indicated a beneficial effect for the children and the educational environment. The potential benefits of teacher implemented behavioural intervention are discussed.

Adolescent↗

PubMed1998

Fluoxetine in treatment of adolescent patients with autism: a longitudinal open trial.

Retrospective chart reviews of seven adolescent and young adults with autistic disorder treated with fluoxetine alone or in combination with other medications were performed. Patient's ages varied from 9-20 years (M +/- SD, = 16 +/- 3.87). Fluoxetine doses ranged from 20-80 mg per day (M +/- SD of final doses 37.14 +/- 21). Duration of treatment ranged from 1.3-32 months (M 18.04 +/- 10.39). Patients' symptoms were monitored using the Aberrant Behavior Checklist (ABC) rating scale during every visit. Side effects included initial appetite suppression, vivid dreams, and hyperactivity. Improvement from baseline was seen in four subscales: irritability (21%), lethargy (37%), stereotype (27%), and inappropriate speech (21%). Lethargy subscales improved significantly during treatment (p < .029). Hyperactivity subscale increased by 14% but did not attain statistical significance. Fluoxetine appears to have important behavioral effects in treatment of clinic-referred autistic children. Future double-blind placebo controlled studies evaluating core and associated symptom response with fluoxetine are warranted.

Adolescent↗

PubMed1999

Vineland Adaptive Behavior Scale scores as a function of age and initial IQ in 210 autistic children.

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.

Activities of Daily Living↗

PubMed1997

[Asperger syndrome--an overview of diagnostic criteria].

Asperger syndrome is an autistic disorder which was first described in 1944 without further acceptance in the literature over almost four decades. Following several publications in the "80's, the disorder became more widely known. Asperger syndrome was introduced into ICD-10 and DSM-IV as a new diagnosis in 1988 and 1994, respectively. Several authors developed own criteria. Until now, some of the diagnostic criteria of Asperger syndrome remain controversial. We present a survey and a comparison of the criteria in the classification of DSM-IV, ICD-10 and of other authors. Six criteria are widely accepted, but there are divergent opinions about the criteria "intelligence" and "speech development".

Autistic Disorder↗

PubMed2005

Trisomy 15q25.2-qter in an autistic child: genotype-phenotype correlations.

We report on the case of a male child with autistic disorder, postnatal overgrowth, and a minor brain malformation. Karyotyping and fluorescent in situ hybridization (FISH) analysis showed the presence of an extra copy of the distal portion of chromosome 15q (15q25.2-qter) transposed to chromosome 15p leading to 15q25.2-qter pure trisomy. This karyotype-phenotype study further supports the evidence for a specific phenotype related to trisomy 15q25 or 26-qter and suggests that distal chromosome 15q may be implicated in specific behavioral phenotypes.

Abnormalities, Multiple↗

PubMed2003

Can the pathophysiology of autism be explained by the nature of the discovered urine peptides?

Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.

Aging↗

PubMed1991

Autism and family home movies: preliminary findings.

Preliminary analyses of 12 home movies taken by parents before the recognition of autistic disorders of their own child confirm the major value of this method for describing early signs: anomalies of eye contact, deficient variability of emotional expression, defect of attention and initiation of communication, motor abnormalities, etc. The possibilities of subsequently using these documents in a research context are described: behavior assignment with a rating scale, comparative analysis with movies of normal children, blind examination, and scoring by investigators not informed of the diagnosis.

Activities of Daily Living↗

PubMed2006

Compulsive masturbation in infantile autism treated by mirtazapine.

This case report describes a child with a severe autistic syndrome worsened by hypersexual behavior consisting of compulsive masturbatory activity. Selective serotonin reuptake inhibitors have been reported to be beneficial in reducing hypersexual behaviors. A treatment with mirtazapine improved the entire clinical autistic picture with the disappearance of masturbation. This result suggests that selective serotonin reuptake inhibitors could be useful and promising tools in the treatment of hypersexual behaviors in children with autistic disorders. Moreover, the general, and in some ways unexpected, improvement of the social interaction, communication, and imagination, the dramatic reduction of aloof mannerisms, stereotypes, aggressiveness, and inappropriate emotional response to frustrations, as well as the first appearance of the pragmatic use of language and a strong impetus to emotional development disclosed a new spectrum of possible applications of these drugs, and mirtazapine in particular, suggesting the need for new and more extensive studies on the pharmacotherapy of autism.

Adrenergic alpha-Antagonists↗

PubMed2005

The treatment of the behavioral sequelae of autism with dextromethorphan: a case report.

Dextromethorphan is the d-isomer of levorphenol, and an ingredient in antitussive preparations. A 10 year-old male diagnosed with Autistic Disorder, Pervasive Developmental Disorder, and Generalized Anxiety Disorder was administered this medication initially to treat a medical condition. This became a quasi-experimental ABAB design (A = baseline, B = treatment), with improvements during treatment phases shown in tracked behavioral data and anecdotal reports. Several candidate mechanisms to explain the improvements are offered, including glutamate receptor antagonism. While dextromethorphan is not commonly administered for the treatment of behavioral challenges in this or any population, the results suggest the need for larger-scale, adequately controlled, and methodologically rigorous studies of the potential clinical effects of dextromethorphan.

Autistic Disorder↗

PubMed1999

Chromosomal abnormalities in child psychiatric patients.

To determine the frequency of chromosomal abnormalities in a child psychiatric population, and to evaluate possible associations between types of abnormalities and patient's clinical characteristics, cytogenetic examination was performed on 604 patients. Demographic data, reasons for karyotyping, clinical signs, and other patient characteristics were assessed and correlated with the results from karyotyping. Chromosomal abnormalities were found in 69 patients (11.3%); these were structural in 49 cases and numerical in 20. Inversion of chromosome nine was found in 15 subjects, trisomy of chromosome 21 in 11, and fragile X in five patients. When karyotyping was performed because of intellectual impairment or multiple developmental delay, significantly more abnormalities were found than average; when performed because autistic disorder was suspected, the number of abnormalities was significantly fewer. There were no differences in clinical variables between structural and numerical abnormalities, nor among nine types of chromosomal abnormalities, except that numerical abnormalities and polymorphism were found at a later age, and that walking was more delayed and IQ was lower in patients with Down syndrome. Clinicians should be aware of the possible presence of chromosomal abnormalities in child psychiatric populations; the close collaboration with geneticists and the use of more defined guidelines for cytogenetic investigation are important.

Adolescent↗

PubMed1998

The preserved speech variant: a subgroup of the Rett complex: a clinical report of 30 cases.

Thirty girls and young women, 6 from Sweden and 24 from Italy, are described in this paper. They ranged in age from 5 through 28 years. All but one of the cases met full symptom criteria for DSM-IV autistic disorder. However, they also showed many features of classic Rett syndrome (RS) as outlined by the Rett syndrome Diagnostic Criteria Work Group. All met the required 3 out of 6 main criteria and 47% also met both these and the required 5 out of 11 supportive criteria for RS variants as outlined by Hagberg. The course of the disorder was more benign than in classic RS, but all the girls were severely functionally impaired. There was familial clustering in a subgroup. It is concluded that these 30 cases represent a syndrome, similar and probably related, to classic RS. It is suggested that there is a spectrum of syndromes ranging from severe cases with classical presentation to considerably milder variants. We propose that, at the present state of knowledge, these conditions might be best categorized as subgroups of the "Rett Complex," in which classical RS and the preserved speech variant may be the most frequent.

Adolescent↗