1. Canitano R, Scandurra V. {{Psychopharmacology in autism: An update}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2011 Jan 15;35(1):18-28.
Autism spectrum disorders are characterized by impairment in social reciprocity, disturbances in language and communication, restricted interests and repetitive behaviors of various types, as defined by the DSM-IV. The neurobiological bases of these disorders are poorly understood, although several abnormalities have been found. Pharmacotherapy in autism spectrum disorders lacks a solid, reliable neurobiological basis and at present it is mainly directed at the so-called associated behavioral symptoms, with limited relevance to core symptoms. Atypical neuroleptics, especially risperidone, have been shown to be useful in the treatment of behavioral symptoms in autism. Recent trials with SSRIs did not show remarkable results, in spite of their promising potential role. Attention deficit and hyperactivity disorder medications may be useful for counteracting the additional features of hyperactivity and short attention span. Antiepileptics have shown promising results but there are no specific indications for them as of yet. Research is now directed at evaluating novel treatments and combined behavioral and pharmacologic treatments, since behavioral interventions are the mainstay of the early treatment of autism. An update of currently available pharmacological treatments is provided.
2. Korvatska O, Estes A, Munson J, Dawson G, Bekris LM, Kohen R, et al. {{Mutations in the TSGA14 gene in families with autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet}. 2011 Jan 13.
Linkage to 7q has been the most robust genetic finding in familial autism. A previous scan of multiplex families with autism spectrum disorders found a linkage signal of genome-wide significance at D7S530 on 7q32. We searched a candidate imprinted region at this location for genetic variants in families with positive linkage scores. Using exon resequencing, we identified three rare potentially pathogenic variants in the TSGA14 gene, which encodes a centrosomal protein. Two variants were missense mutations (c.664C>G; p.P206A and c.766T>G; p.C240G) that changed conserved residues in the same protein domain; the third variant (c.192+5G>A) altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare TSGA14 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher’s exact two tailed P = 0.022). This is the first report of a possible link of a gene with a centrosomal function with familial autism. (c) 2011 Wiley-Liss, Inc.
3. Matsuishi T, Yamashita Y, Takahashi T, Nagamitsu S. {{Rett syndrome: The state of clinical and basic research, and future perspectives}}. {Brain Dev}. 2011 Jan 11.
To clarify the pathophysiology of brain and spinal cord impairment in Rett syndrome (RTT), we report on the current status of research on Rett syndrome and review the abnormalities reported in neurotransmitters, neuromodulators and other biological markers in patients with RTT. We have previously investigated the levels of various factors in the blood, plasma, and cerebrospinal fluid (CSF) of RTT patients, including biogenic amines, lactate, melatonin, pyruvate and other citric acid cycle intermediates, substance P, beta-endorphin and other neuropeptides, and a neuromodulator of beta-phenylethylamine. In addition, we have performed near-infrared spectroscopy of the cerebral cortices in patients with RTT and genetic studies of the methyl-CpG-binding protein 2 (MECP2) in these patients. Taken together, the multiple abnormalities we and other authors have revealed in the various neurotransmitters/neuromodulator systems explain the pervasive effects of Rett syndrome. We also discuss the possible role of plasma ghrelin and present the results of our mouse study of the MECP2-null mutation using ES cells. Finally, we consider the potential for future analyses using our recently developed iPS cell system and discuss the future perspectives for the treatment and management of this disease.
4. Mironov SL, Skorova EY, Kugler S. {{Epac-mediated cAMP-signalling in the mouse model of Rett Syndrome}}. {Neuropharmacology}. 2011 Jan 10.
Rett Syndrome (RTT) is a neurodevelopmental disease thought to be caused by deficits in synaptogenesis and neuronal circuitry. cAMP is one of the key factors for neuronal outgrowth, plasticity and regeneration. We examined its homeostasis in RTT during early postnatal development of the essential part of the respiratory network, pre-Botzinger complex. Using targeted expression of Epac1-camps sensor in neurons we quantified cAMP levels and their fluctuations in MeCP2-/y mice, an established model of RTT. Resting cAMP levels in the mutant were smaller than in the wild-type. cAMP transients elicited by depolarisation and stimulation of adenylate cyclase had also smaller amplitudes and faster time-courses. The anomalies in MeCP2 -/y mice were removed after inhibition of phosphodiesterase PDE4 with rolipram. Brief cAMP elevations triggered elongation of neuronal processes that was significantly bigger in the wild-type. The effects were observed after inhibition of protein kinase A and mimicked by activation of a guanine nucleotide exchange factor, Epac, with 8-(4-Chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8-pCPT). The agonist reinforced bursting in preBotC neurons in the mutant and converted it to the wild-type. All actions of 8-pCPT were not reproduced by its non-active analogue and abolished by Epac signalling inhibitor Brefeldin A. We propose that disturbances in cAMP homeostasis in MeCP2 -/y mice can lead to inadequate Epac signalling. Concomitant defective development of respiratory circuits may be responsible for irregular breathing activity in RTT.
5. Ronald A, Hoekstra RA. {{Autism spectrum disorders and autistic traits: A decade of new twin studies}}. {Am J Med Genet B Neuropsychiatr Genet}. 2011 Jan 13.
Researchers continue to pursue a better understanding of the symptoms, comorbidities, and causes of autism spectrum disorders. In this article we review more than 30 twin studies of autism spectrum disorders (ASDs) and autistic traits published in the last decade that have contributed to this endeavor. These twin studies have reported on the heritability of autism spectrum disorders and autistic traits in different populations and using different measurement and age groups. These studies have also stimulated debate and new hypotheses regarding why ASDs show substantial symptom heterogeneity, and what causes their comorbidity with intellectual disability, language delay, and other psychiatric disorders such as ADHD. These studies also reveal that the etiology of autism and autistic traits assessed in the general population is more similar than different, which contributes to the question of where the boundary lies between autism and typical development. Recent findings regarding molecular genetic and environmental causes of autism are discussed in the relation to these twin studies. Lastly, methodological assumptions of the twin design are given consideration, as well as issues of measurement. Future research directions are suggested to ensure that this decade is as productive as the last in attempting to disentangle the causes of autism spectrum disorders. (c) 2011 Wiley-Liss, Inc.
6. Wachtel LE, Reti IM, Dhossche DM, Slomine BS, Sanz J. {{Stability of neuropsychological testing during two years of maintenance electroconvulsive therapy in an autistic man}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2011 Jan 15;35(1):301-2.
7. Zeidan-Chulia F, Gursoy UK, Kononen E, Gottfried C. {{A dental look at the autistic patient through orofacial pain}}. {Acta Odontol Scand}. 2011 Jan 13.
Abstract Autism is a neurodevelopmental disorder characterized by impaired social interaction and restricted interests, compromised communication skills, and repetitive patterns of behavior. Both social and behavioral problems, which may include hyperactivity and quick frustration, may hinder the detection of other important pathologies such as orofacial pain. This is aggravated by the invasive nature of oral exploration, which may trigger violent and self-injurious responses, such as temper tantrums and/or head banging, which make the work of professionals extremely difficult during diagnoses, follow-up examinations, and dental treatments. In addition, mercury-containing amalgams used to treat dental caries (the most common form of acute orofacial pain) have been associated with higher rates of severe autism in children. The purpose of this review is to describe the current state of the art regarding the co-occurrence of orofacial pain and autism spectrum disorder, and how these conditions may interrelate clinically and neurobiologically.
