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Abstract Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 CAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)[sub 67] mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild-type littermates. We show that GAD[sub 67] expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease. [ABSTRACT FROM AUTHOR]

On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of␣abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization. [ABSTRACT FROM AUTHOR]

AIM: During adolescence, some individuals with autism engage in severe disruptive behaviors, such as violence, agitation, tantrums, or self-injurious behaviors. We aimed to assess risk factors associated with very acute states and regression in adolescents with autism in an inpatient population. METHOD: Between 2001 and 2005, we reviewed the charts of all adolescents with autism (N=29, mean age=14.8 years, 79% male) hospitalized for severe disruptive behaviors in a psychiatric intensive care unit. We systematically collected data describing socio-demographic characteristics, clinical variables (severity, presence of language, cognitive level), associated organic conditions, etiologic diagnosis of the episode, and treatments. RESULTS: All patients exhibited severe autistic symptoms and intellectual disability, and two-thirds had no functional verbal language. Fifteen subjects exhibited epilepsy, including three cases in which epilepsy was unknown before the acute episode. For six (21%) of the subjects, uncontrolled seizures were considered the main cause of the disruptive behaviors. Other suspected risk factors associated with disruptive behavior disorders included adjustment disorder (N=7), lack of adequate therapeutic or educational management (N=6), depression (N=2), catatonia (N=2), and painful comorbid organic conditions (N=3). CONCLUSION: Disruptive behaviors among adolescents with autism may stem from diverse risk factors, including environmental problems, comorbid acute psychiatric conditions, or somatic diseases such as epilepsy. The management of these behavioral changes requires a multidisciplinary functional approach. [ABSTRACT FROM AUTHOR]