Pubmed du 28/04/09

mardi 28 avril 2009

1. Desjardins S, Doyen C, Contejean Y, Kaye K, Paubel P. [Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form.]. Encephale ;2009 (Apr) ;35(2):168-172.Traitement d’un enfant autiste par la naltrexone.

CLINICAL BACKGROUND : Autism is a developmental disorder that is usually diagnosed in early childhood. According to ICD-10 criteria, autism can be characterized by delays in language skills, by impaired social interaction, verbal or non-verbal communication and by repetitive, stereotyped or severely restricted activities and interests. The causes of autism are not yet elucidated, but both genetics and environment seem to play a role in 10 to 25% of autism cases. Several biochemical abnormalities, such as impairment of serotoninergic, catecholinergic, dopaminergic, and opioid systems have been reported. Autism therapies are designed to treat symptoms, and medication can be associated with psychoeducational and environmental interventions. Generally, the medications that are currently used are not intended for autism, and must be used with caution and selected according to the type and intensity of symptoms. The most common medication consists of psychotropic therapies by administration of dopaminergic and/or serotoninergic receptor antagonists (haloperidol, risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid antagonists (naltrexone) can be prescribed, in second intention, in cases of severe behavioural disorders. The prescription of opioid antagonists is based on the possible implication of an opioid system disorder observed in some cases. Nevertheless, several clinical studies reveal its variable effectiveness. Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and OPRK1. In France, this drug is prescribed for treating opioid and alcohol dependence. Moreover, several studies describe naltrexone as a possible treatment of autistic children in cases of developmental disorder and hyperactivity. CLINICAL CASE : In the Child and Adolescent Psychopathology Department of Sainte-Anne’s Hospital, autistic children benefit from a multidisciplinary treatment program that sometimes includes the administration of psychotropic medication. One of these children presented with a severe autistic disorder according to the Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited from a multidisciplinary program, associating cognitive psychotherapy, psychomotor rehabilitation, speech therapy and educational intervention. However, persistent sleep disorder and motor instability led to successive prescriptions of several different psychotropic drugs. Initial treatment by thioridazine (10mg per day) followed by propericiazine (2.5mg per day) improved sleep, but was not efficient in reducing self-mutilating behaviour. A new treatment by risperidone (from 0.5mg to 1.5mg per day) was therefore chosen ; however it lost its efficacy after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator (sodium valproate) were successively tried without yielding any clinical improvement. Owing to the persistence of communication difficulties, major instability, self-mutilating behaviour and heteroaggressiveness, treatment with naltrexone was subsequently chosen with parental consent. In France, naltrexone hydrochloride is only available in tablet form (Nalorex((R)) 50mg and Revia((R)) 50mg), which is not adapted to children at the efficient dose. Consequently, an oral suspension form marketed in Spain (Antaxone((R)) 50mg) was imported, having obtained the Afssaps’ (the French drug administration) authorisation for its temporary use. The Connors and Nisonger scales were used as outcome measures of behavioural symptom change. The Conners scale is used to assess attention deficit and hyperactivity, whereas the Nisonger scale analyses social skills and behaviour disorders in children and adolescents with mental retardation. The onset of treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant improvements, as shown by outcome measurements. Self-mutilating behaviour disappeared completely. Certain side effects were observed, namely transitory sedation at the beginning of treatment and moderate constipation. CONCLUSION : This clinical case confirms that treatment of a serious autistic disorder in children using Naltrexone in oral suspension form is a potentially interesting therapeutic alternative for treating behavioural symptoms resistant to classical drug therapy.

2. Dichter GS, Lam KS, Turner-Brown LM, Holtzclaw TN, Bodfish JW. Generativity Abilities Predict Communication Deficits but not Repetitive Behaviors in Autism Spectrum Disorders. J Autism Dev Disord ;2009 (Apr 25)

Individuals with Autism Spectrum Disorders (ASD) often demonstrate impaired generativity that is thought to mediate repetitive behaviors in autism (Turner in J Child Psychol Psychiatry, 40(6):839-849, 1999a). The present study evaluated generativity in children with and without ASD via the use-of-objects task (Turner in J Child Psychol Psychiatry, 40(2):189-201, 1999b) and an Animals Fluency Task (Lezak in Neuropsychological assessment. Oxford University Press, Oxford, 1995). Groups differed significantly on two of four metrics from the Animals Fluency Task and two of seven metrics from the Use of Objects task. In the ASD sample, no significant relations were found between generativity and repetitive behaviors. Significant relations were found, however, between performance on the Animals Fluency Task and communication symptoms. Results replicate reports of generativity deficits in ASD and suggest that impaired generativity may reflect communication deficits that are characteristic of the disorder.

3. Fombonne E. A wrinkle in time : from early signs to a diagnosis of autism. J Am Acad Child Adolesc Psychiatry ;2009 (May) ;48(5):463-464.

4. Jones W, Klin A. Heterogeneity and homogeneity across the autism spectrum : the role of development. J Am Acad Child Adolesc Psychiatry ;2009 (May) ;48(5):471-473.

5. Katz DM, Dutschmann M, Ramirez JM, Hilaire G. Breathing Disorders in Rett Syndrome : Progressive Neurochemical Dysfunction in the Respiratory Network after Birth. Respir Physiol Neurobiol ;2009 (Apr 23)

Disorders of respiratory control are a prominent feature of Rett syndrome (RTT), a severely debilitating condition caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). RTT patients present with a complex respiratory phenotype that can include periods of hyperventilation, apnea, breath holds terminated by Valsalva maneuvers, forced and deep breathing and apneustic breathing, as well as abnormalities of heart rate control and cardiorespiratory integration. Recent studies of mouse models of RTT have begun to shed light on neurologic deficits that likely contribute to respiratory dysfunction including, in particular, defects in neurochemical signaling resulting from abnormal patterns of neurotransmitter and neuromodulator expression. The authors hypothesize that breathing dysregulation in RTT results from disturbances in mechanisms that modulate the respiratory rhythm, acting either alone or in combination with more subtle disturbances in rhythm and pattern generation. This article reviews the evidence underlying this hypothesis as well as recent efforts to translate our emerging understanding of neurochemical defects in mouse models of RTT into preclinical trials of potential treatments for respiratory dysfunction in this disease.

6. Olsen J, Zhu JL. Re : "Advanced Parental Age and the Risk of Autism Spectrum Disorder". Am J Epidemiol ;2009 (Apr 24)

7. Sizoo BB, van den Brink W, Gorissen-van Eenige M, Koeter MW, van Wijngaarden-Cremers PJ, van der Gaag RJ. Using the Autism-Spectrum Quotient to Discriminate Autism Spectrum Disorder from ADHD in Adult Patients With and Without Comorbid Substance Use Disorder. J Autism Dev Disord ;2009 (Apr 25)

It is unknown whether the Autism-spectrum quotient (AQ) can discriminate between Autism Spectrum Disorder (ASD) and Attention Deficit and Hyperactivity Disorder (ADHD) with or without comorbid Substance Use Disorder (SUD). ANOVA’s were used to analyse the mean AQ (sub)scores of 129 adults with ASD or ADHD. We applied receiver operating characteristic (ROC) computations to assess discriminant power. All but one of the mean AQ (sub)scores were significantly higher for adults with ASD compared to those with ADHD. The SUD status in general was not significantly associated with AQ (sub)scores. On the Social Skills subscale patients with ASD and comorbid SUD showed less impairment than those without SUD. The cut-off score 26 yielded 73% correct classifications. The clinical use of the AQ in differentiating between ASD and ADHD is limited.


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