1. Bromley RL, Mawer G, Clayton-Smith J, Baker GA. {{Autism Spectrum Disorders Following in Utero Exposure to Antiepileptic Drugs}}. {Neurology};2008 (Dec 2);71(23):1923-1924.On behalf of the Liverpool and Manchester Neurodevelopment Group
2. Brown N, Panksepp J. {{Low-dose naltrexone for disease prevention and quality of life}}. {Med Hypotheses};2008 (Nov 26)
The use of low-dose naltrexone (LDN) for the treatment and prophylaxis of various bodily disorders is discussed. Accumulating evidence suggests that LDN can promote health supporting immune-modulation which may reduce various oncogenic and inflammatory autoimmune processes. Since LDN can upregulate endogenous opioid activity, it may also have a role in promoting stress resilience, exercise, social bonding, and emotional well-being, as well as amelioration of psychiatric problems such a autism and depression. It is proposed that LDN can be used effectively as a buffer for a large variety of bodily and mental ailments through its ability to beneficially modulate both the immune system and the brain neurochemistries that regulate positive affect.
3. Canitano R, Scandurra V. {{Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents}}. {Neuropsychiatr Dis Treat};2008 (Aug);4(4):723-730.
This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review.
4. Howlett E, Lin CC, Lavery W, Stern M. {{A PI3-Kinase-Mediated Negative Feedback Regulates Neuronal Excitability}}. {PLoS Genet};2008 (Nov);4(11):e1000277.
Use-dependent downregulation of neuronal activity (negative feedback) can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. Disruption of this negative feedback might lead to neurological pathologies, such as epilepsy, but the precise mechanisms by which this feedback can occur remain incompletely understood. At one glutamatergic synapse, the Drosophila neuromuscular junction, a mutation in the group II metabotropic glutamate receptor gene (DmGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that DmGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in a DmGluRA-dependent manner. Finally, we show that PI3K increases both axon diameter and synapse number via the Tor/S6 kinase pathway, but not Foxo. In humans, PI3K and group II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia, and other neurological disorders; however, neither the link between group II mGluRs and PI3K, nor the role of PI3K-dependent regulation of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability.
5. Oliver C, Arron K, Sloneem J, Hall S. Behavioural phenotype of Cornelia de Lange syndrome: case-control study. Br J Psychiatry;2008 (Dec);193(6):466-470.
BACKGROUND: Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. AIMS: To delineate the behavioural phenotype of Cornelia de Lange syndrome with specific reference to autistic-spectrum disorder. METHOD: A total of 54 individuals with Cornelia de Lange syndrome (mean age 13.88 years; s.d.=8.58) and 46 comparable individuals with intellectual disability (mean age 13.74 years; s.d.=7.99) were assessed on measures of autistic-spectrum disorder, and adaptive, compulsive and disordered behaviour. RESULTS: There was no difference between the groups in global behaviour disorder. Severe autism was significantly more prevalent in the syndrome group (32.1%) than the comparison group (7.1%). In addition, the syndrome group also evidenced significantly higher levels of compulsive behaviour. CONCLUSIONS: These data suggest that autistic-spectrum disorder is part of the behavioural phenotype of Cornelia de Lange syndrome and that compulsive behaviours are evident. Future research should investigate this behavioural phenotype using contemporary diagnostic algorithms for autism with detailed examination of the phenomenology of compulsive behaviours.
6. Takeuchi Y. {{[Neurotransmission in developmental disorders]}}. {No To Hattatsu};2008 (Nov);40(6):451-455.
Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse (« volume transmission »). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child neurology medical examination and treatment should be based on the basic neuroscience, always taking « neurons » into consideration.
7. Towle PO, Visintainer PF, O’Sullivan C, Bryant NE, Busby S. {{Detecting Autism Spectrum Disorder from Early Intervention Charts: Methodology and Preliminary Findings}}. {J Autism Dev Disord};2008 (Dec 2)
8. Weissman JR, Kelley RI, Bauman ML, Cohen BH, Murray KF, Mitchell RL, Kern RL, Natowicz MR. {{Mitochondrial disease in autism spectrum disorder patients: a cohort analysis}}. {PLoS ONE};2008;3(11):e3815.
BACKGROUND: Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity. CONCLUSIONS/SIGNIFICANCE: Although all patients’ initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.
