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BACKGROUND: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene-dosage effects on language development at 7q11.23 have been hypothesized. METHODS: Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. RESULTS: The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. CONCLUSIONS: Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype-phenotype correlations, possible gene-environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism.

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UNLABELLED: We examined the understanding of emotional speech by children and adolescents with autism spectrum disorders (ASD). We predicted that they would have difficulty understanding emotional speech, not because of an emotional prosody processing impairment but because of problems drawing appropriate inferences, especially in multiple-cue environments. Twenty-six children and adolescents with ASD and 26 typically developing controls performed a computerized task featuring emotional prosody, either embedded in a discrepant context or without any context at all. They must identify the speaker's feeling. When the prosody was the sole cue, participants with ASD performed just as well as controls, relying on this cue to infer the speaker's intention. When the prosody was embedded in a discrepant context, both ASD and TD participants exhibited a contextual bias and a negativity bias. However ASD participants relied less on the emotional prosody than the controls when it was positive. We discuss these findings with respect to executive function and intermodal processing. LEARNING OUTCOMES: After reading this article, the reader should be able to (1) describe the ASD participants pragmatic impairments, (2) explain why ASD participants did not have an emotional prosody processing impairment, and (3) explain why ASD participants had difficulty inferring the speaker's intention from emotional prosody in a discrepant situation.

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Aripiprazole inaugurates a new generation of antipsychotics called dopamine-serotonin system stabilizers. Its mechanism of action is different as aripiprazole is a partial dopamine D(2) and serotonin 5-HT(1A) receptor agonist and 5-HT(2A) receptor antagonist. Therefore, aripiprazole is thought to have an antagonistic action in the mesolimbic pathway but an agonistic action in the mesocortical pathway, tending to normalize the dopaminergic transmission regardless of the type of imbalance. Clinical trials involving children and adolescents have demonstrated the efficacy of aripiprazole in bipolar disorders, schizophrenia, mood disorders associated with pervasive developmental disorders, in tics and Tourette's. The most frequent side effects are extrapyramidal symptoms and sleepiness and are dose-dependent. Nevertheless, contrary to other second-generation antipsychotics available in France, it induces little weight gain, does not modify lipid and glucidic profiles, does not increase prolactin levels, or induce QTc lengthening. The main advantage of aripiprazole is its good safety profile, with different toxicity targets to other second-generation antipsychotics available in France. Aripiprazole appears to be an alternative for children and adolescents who are vulnerable to these side effects and are having trouble coping with them.

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Aripiprazole inaugurates a new generation of antipsychotics called dopamine-serotonin system stabilizers. Its mechanism of action is different as aripiprazole is a partial dopamine D2 and serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist. Therefore, aripiprazole is thought to have an antagonistic action in the mesolimbic pathway but an agonistic action in the mesocortical pathway, tending to normalize the dopaminergic transmission regardless of the type of imbalance. Clinical trials involving children and adolescents have demonstrated the efficacy of aripiprazole in bipolar disorders, schizophrenia, mood disorders associated with pervasive developmental disorders, in tics and Tourette's. The most frequent side effects are extrapyramidal symptoms and sleepiness and are dose-dependant. Nevertheless, contrary to other second-generation antipsychotics available in France, it induces little weight gain, does not modify lipid and glucidic profiles, does not increase prolactin levels, or induce QTc lengthening. The main advantage of aripiprazole is its good safety profile, with different toxicity targets to other secondgeneration antipsychotics available in France. Aripiprazole appears to be an alternative for children and adolescents who are vulnerable to these side effects and are having trouble coping with them.

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Sleep disturbances are frequent in children and adolescents with psychiatric disorders nevertheless there are few drugs available to treat them. Only certain antihistaminic H1 have the marketing authorization for treatment of childhood insomnia. Very few studies have been made in children about the hypnotics that are most widely used in adult patients: zopiclone, zolpidem and the hypnotic benzodiazepines. However, melatonin has recently become the most studied hypnotic drug in children since the marketing of a sustained-released form gave it the status of a drug and improved its pharmacokinetic properties. In child psychiatry, pharmacological treatment of insomnia should be considered in patients with attention deficit hyperactivity disorder in which sleep disturbances can be aggravated by psycho stimulant treatment, in autism spectrum disorders, and in the anxiety/depression.

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Sleep disturbances are frequent in children and adolescents with psychiatric disorders nevertheless there are few drugs available to treat them. Only certain antihistaminic H1 have the marketing authorization for treatment of childhood insomnia. Very few studies have been made in children about the hypnotics that are most widely used in adult patients: zopiclone, zolpidem and the hypnotic benzodiazepines. However, melatonin has recently become the most studied hypnotic drug in children since the marketing of a sustained-released form gave it the status of a drug and improved its pharmacokinetic properties. In child psychiatry, pharmacological treatment of insomnia should be considered in patients with attention deficit hyperactivity disorder in which sleep disturbances can be aggravated by psycho stimulant treatment, in autism spectrum disorders, and in the anxiety/depression.

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In a plural and multidisciplinary process of care, it would be fruitful to ally complementary, pharmacologic and psychodynamic approaches. We have done a review of the literature on the effectiveness and the cautions for prescription of risperidone, a second generation antipsychotic drug. Risperidone has proved helpful in treating children and adolescents with autism spectrum, conduct and bipolar disorders, Tourette's syndrome, and schizophrenia. The principal side effects are sedation, weight gain, and metabolic disturbances. Extrapyramidal symptoms, QTc prolongation, and hyperprolactemia with clinical signs are infrequent and not clinically significant. The benefit/risk is clearly in favor of the prescription when it is accompanied with the precautions and with the adequate monitoring.

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