Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature. 1 Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism. 1 For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the ␥-aminobutyric acid type-A receptor ␤3 subunit gene (GABRB3) has been associated in one study 2 but not others. [3][4][5] We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder. Molecular Psychiatry ( Autism is a development disorder characterized by impairments in three domains: communication, reciprocal social interactions, and repetitive or stereotyped behaviors and interests (for review see TagerFlusberg et al 1 ). The concordance rate for monozygotic twins is much higher than that of dizygotic twins, which indicates that genetic factors play an important role in the etiology of autism. In addition, family studies indicate that the recurrence risk to siblings, estimated from multiple studies at 1-3%, is profoundly higher than the risk to the general population, which has been estimated at ෂ0.5-2 per 1000. The mode of inheritance of autism appears to be complex; latentclass analyses suggest that 3-10 genes may underlie the disorder, 6 although an interpretation of at least one genome-wide linkage analysis has argued for Ͼ10 genes underlying the disorder. 7 Cytogenetic studies have demonstrated that duplications within the 15q11-q13 region can be associated with autism (for review see Tager-Flusberg et al 1 ). Moreover, symptoms of autism can be associated with both Prader-Willi and Angelman syndromes, both of which involve alterations in the 15q11-q13 region. Because of this, the15q11-q13 region has been examined for genetic linkage to autism. A mapping of nine markers spanning a region of ෂ2 Mb within this region in 132 families demonstrated linkage disequilibrium at a marker within the GABRB3 gene, 155CA-2. 2 An additional locus within GABRB3 that is ෂ150 kb away from 155CA-2 (D15S97) did not demonstrate linkage disequilibrium.A genome-wide scan involving 51 autistic multiplex families demonstrated a broad peak with a LOD score of about 1 over the GABRB3 region. 8 Similarly, multipoint analyses over the region in 63 families demonstrated a peak Z-score of 1.78 in the region, near the marker ...

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Chronic schizophrenic patients with the most severe social deterioration have been shown to differ from other chronic schizophrenic patients with respect to measures of left-to-right ventricular asymmetry, negative symptoms, and response to haloperidol treatment. In the current study, the authors investigated the social antecedents of these characteristics of very poor outcome schizophrenia in 69 chronic schizophrenic patients. Poor premorbid sociosexual functioning was associated with more severe left-to-right ventricular asymmetry, greater severity of negative symptoms, fewer positive symptoms, and worse current social functioning. These data suggest that factors associated with severe social deterioration in the end stage of schizophrenia are also associated with premorbid sociosexual impairment.

Poster abstracts / Int. J. Devl Neuroscience 24 (2006) 495-603 507 oxidant-and inflammatory-mediated diseases, including brain aging.In the present study we report that treatment for 4 months of senescent rats with Acetylcarnitine (LAC) is able to induce heme oxygenase-1, Hsp70 and SOD-2, and that this effect is associated with up-regulation of GSH levels. In addition, by using redox proteomics, we provide a valuable insight into the mechanism of age-related protein oxidation and the effect of LAC in reducing oxidative stress associated with functional impairment in aged brains.Redox proteomics analysis of hippocampus (HP) and cerebral cortex (CX), brain regions in which all indices of oxidative modification are elevated in brain aging showed that the specific carbonyl levels of three proteins, hemoglobin, cofilin 1 and beta-actin, are significantly increased in HP of senescent rats. All specific carbonyl levels of these proteins are reduced by LAC administration in old rats. In the CX of senescent rats, the specific carbonyl levels of eight proteins: heat shock protein 70, glyoxylase 1, beta-actin, 3-mercaptopyruvate sulfurtransferase, peroxiredoxin 1, phosphoribosyl pyrophosphate synthetase 1, and fumarase, were increased. LAC administration was able to reduce the specific carbonyl levels of all these proteins which are involved in three impaired processes in aged brains: antioxidant defence, mitochondrial function and synaptic plasticity. Treatment by LAC may improve the decline of these functions and therefore LAC could be considered as a potential therapeutic agent for treatment of cognitive decline in aging. Therapeutic strategies focussing on acetylcarnitine treatment may represent a crucial mechanism of defence against free radical-induced damage of critical proteins occurring in aging brain.Fragile X syndrome is a common cause of inherited mental retardation. In addition to cognitive defects, many patients display hyperactivity and autistic-like behaviour. The syndrome is caused by the absence of the FMR1 protein (FMRP) and the fmr1-knockout mice (fmr1-KO mice) serve as a mouse model for the syndrome. The transgenic mice exhibit elevated susceptibility to audiogenic seizures and tendency to spend significantly more time in the center of an open field than the wild-type mice do. These phenotypes were shown to be suppressed by the treatment with metabotropic glutamate receptor antagonist, MPEP. We have previously shown that the differentiation of neural stem cells (NSCs) is altered in fragile X syndrome. An increase in the number of cells with metabotropic glutamate response was a unique feature in the differentiation of FMRP-deficient NSCs.We investigated the effects of MPEP on growth and differentiation of NSCs in neurosphere cultures generated from brains of the fmr1-KO mice using the MTT assay and calcium imaging. Treatment with 1-10 M MPEP did not affect growth of proliferating wild-type or FMRP-deficient mouse NSCs. However, treatment with 100 M MPEP caused a significant reduction in the cell ...