HTR1B and HTR2C in autism spectrum disorders in Brazilian families

Autism spectrum disorders (ASD) is a group of behaviorally defined neuro developmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD. (C) 2008 Elsevier B.V. All rights reserved.

Deficiency of the Cytoskeletal Protein SPECC1L Leads to Oblique Facial Clefting

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L. are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Speed 1 1 is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.

Temporal lobe epilepsy and social behavior: An animal model

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology. (c) 2008 Elsevier Inc. All rights reserved.

Saliva flow rate, buffer capacity, and pH of autistic individuals

The objective of the study was to evaluate saliva flow rate, buffer capacity, pH levels, and dental caries experience (DCE) in autistic individuals, comparing the results with a control group (CG). The study was performed on 25 noninstitutionalized autistic boys, divided in two groups. G1 composed of ten children, ages 3-8. G2 composed of 15 adolescents ages 9-13. The CG was composed of 25 healthy boys, randomly selected and also divided in two groups: CG3 composed of 14 children ages 4-8, and CG4 composed of 11 adolescents ages 9-14. Whole saliva was collected under slight suction, and pH and buffer capacity were determined using a digital pHmeter. Buffer capacity was measured by titration using 0.01 N HCl, and the flow rate expressed in ml/min, and the DCE was expressed by decayed, missing, and filled teeth (permanent dentition [DMFT] and primary dentition [dmft]). Data were plotted and submitted to nonparametric (Kruskal-Wallis) and parametric (Student`s t test) statistical tests with a significance level less than 0.05. When comparing G1 and CG3, groups did not differ in flow rate, pH levels, buffer capacity, or DMFT. Groups G2 and CG4 differ significantly in pH (p = 0.007) and pHi = 7.0 (p = 0.001), with lower scores for G2. In autistic individuals aged 3-8 and 9-13, medicated or not, there was no significant statistical difference in flow rate, pH, and buffer capacity. The comparison of DCE among autistic children and CG children with deciduous (dmft) and mixed/permanent decayed, missing, and filled teeth (DMFT) did not show statistical difference (p = 0.743). Data suggest that autistic individuals have neither a higher flow rate nor a better buffer capacity. Similar DCE was observed in both groups studied.

Early Onset Obsessive-Compulsive Disorder With and Without Tics

Introduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the ""early onset"" group (EOG): before 11 years of age, 75 patients had an ""intermediate onset"" (IOG), and 95 patients were from the ""late onset"" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale; and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. Results: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the ""aggression/violence"" and ""miscellaneous"" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the ""contamination/cleaning"" dimension. Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics. CNS Spectr. 2009; 14(7):362-370