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Background: Velo-cardio-facial syndrome (VCFS) is associated with interstitial deletions of chromosome 22q11. About 30% of patients with VCFS have psychosis, and the rate of these deletions in schizophrenia has been reported to be about 1%. Even higher rates of VCFS deletions have been reported for childhood-onset schizophrenia.Aims: To test the hypothesis that there is an increased rate of VCFS among patients with early-onset psychosis (age at onset <18 years). We screened 192 early-onset patients and 329 patients with adult-onset schizophrenia.Method: We genotyped the patients and 444 healthy controls for hemizygosity of five microsatellite markers and one single nucleotide polymorphism that map to the 22q11-deleted region.Results: One patient had a VCFS deletion, confirmed with semi-quantitative polymerase chain reaction. None of the controls showed a pattern of genotypes consistent with hemizygosity.Conclusions: VCFS may be less frequent among patients with psychosis than previously suggested; this rate is not increased among early-onset patients. [ABSTRACT FROM AUTHOR]

Background: Evidence exists for an association between aggression and schizophrenia. Although the aetiology of aggression is multifactorial, three studies have reported associations between polymorphisms of the catechol-O-methyltransferase (COMT) gene and aggression in schizophrenia.Aims: To replicate these findings in a larger sample using the Overt Aggression Scale (OAS).Method: A sample of 180 people with DSM-IV schizophrenia were rated for aggression using the OAS. Kruskal-Wallis and contingency table analyses were applied to the OAS results.Results: The high-activity homozygotes showed significantly higher scores of aggression, whereas the heterozygotes showed significantly lower scores. The odds ratio for aggression for the high-activity homozygotes was 2.07 (95% Cl=1.03-4.15), whereas that for the heterozygotes was 0.54 (95% Cl=0.30-1.00). CONCLUSIONS; The high-activity COMT homozygote confers a higher risk of recorded aggression in schizophrenia. Heterozygotes had a significantly lower risk, which may represent an example of heterosis/heterozygote advantage. [ABSTRACT FROM AUTHOR]

For two cohorts of children from low- to moderate-income families, time-use diaries of television viewing were collected over 3 years (from ages 2-5 and 4-7 years, respectively), and tests of reading, math, receptive vocabulary, and school readiness were administered annually. Relations between viewing and performance were tested in path analyses with controls for home environment quality and primary language (English or Spanish). Viewing child-audience informative programs between ages 2 and 3 predicted high subsequent performance on all four measures of academic skills. For both cohorts, frequent viewers of general-audience programs performed more poorly on subsequent tests than did infrequent viewers of such programs. Children's skills also predicted later viewing, supporting a bidirectional model. Children with good skills at age 5 selected more child-audience informative programs and fewer cartoons in their early elementary years. Children with lower skills at age 3 shifted to viewing more general-audience programs by ages 4 and 5. The results affirm the conclusion that the relations of television viewed to early academic skills depend primarily on the content of the programs viewed. [ABSTRACT FROM AUTHOR]

Background: Velo-cardio-facial syndrome (VCFS) is associated with deletions in the qll band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood.Aims: To investigate brain anatomy in adults with VCFS.Method: Magnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume.Results: The subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes.Conclusions: Deletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS. [ABSTRACT FROM AUTHOR]

Background Velo-cardio-facial syndrome (VCFS), a syndrome of multiple congenital abnormalities including characteristic dysmorphology, congenital heart defects and learning disability, is associated with small interstitial deletions of chromosome 22q11. We tested the hypothesis that VCFS may be significantly under-diagnosed by screening a learning-disabled population for chromosome 22q11 deletions. Method Two hundred and sixty-five people with learning disability residing in two earning disability hospitals in South Wales were reviewed. They were selected for inclusion in the study if they fulfilled any of the following criteria: psychotic disorder (schizophrenia or affective disorder), family history of psychotic disorder, cleft palate and/or lip, congenital heart disease, broadly defined facial dysmorphism or a history of hypocalcaemia. Fluorescence in situ hybridisation studies were performed on 74 selected individuals. Results Cytogenetic analysis revealed that two people demonstrated a previously undetected chromosome 22q 11 deletion. A third person demonstrated a previously undetected cytogenetically visible deletion on chromosome 15. Conclusions VCFS appears to be aetiologically significant in a proportion of individuals with idiopathic learning disability, especially in those where psychosis is associated with mild learning disability. We suggest that clinicians should consider a chromosome 22q11 deletion in people who meet selection criteria. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia.Method: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist. Patient's maximum CAG/CTG repeat length was measured using repeat expansion detection (RED). Significant differences were sought for repeat lengths in subjects categorised according to dimensional and categorical schizophrenia subsyndromes, affective episodes, individual symptoms, and a range of demographic variables.Results: Maximum CAG/CTG repeat length did not differ significantly for any of the clinical or demographic variables studied.Conclusion: There are no subsyndromes or other clinical features of schizophrenia associated with CAG/CTG repeat expansion. Therefore, the identification of the gene(s) that contain expanded CAG/CTG repeats and which are associated with schizophrenia is unlikely to be facilitated at present by using any subsyndromes of schizophrenia as phenotypes. [ABSTRACT FROM AUTHOR]

Background Abnormalities presumed to occur during foetal life have been associated with schizophrenia. Polydactyly is a developmental abnormality but no previous association has been reported between polydactyly and functional psychotic illness, Method Individuals with both polydactyly and a functional psychosis were ascertained during a study of familial schizophrenia. Results Five such individuals were ascertained in the course of assessing 234 individuals with familial psychosis, giving a rate of polydactyly in the sample of around 10 times the general population rate. Conclusions This study provides preliminary evidence that polydactyly is over-represented in individuals with familial schizophrenia and related psychotic illnesses. [ABSTRACT FROM AUTHOR]

22q11 Deletion Syndrome (22q11DS) is a relatively common interstitial deletion disorder with a minimum prevalence of approximately 1:5000 live births. Although considerable phenotypic variability occurs, common clinical features include a typical dysmorphology, cleft palate, congenital heart defects and a characteristic behavioural phenotype. While much of the literature has focussed on the well documented association between 22q11DS and schizophrenia, there is now increasing attention on the prevalence of autistic spectrum disorders (ASD) in 22q11DS. The current evidence implicating ASD in 22q11DS and the implications for the clinical management of affected individuals will be discussed. [ABSTRACT FROM AUTHOR]

Background: Velocardiofacial Syndrome (VCFS) is the most common human genetic deletion syndrome and young people with VCFS are at substantial risk for developing psychosis in later life. It has been reported that people with VCFS have significant differences in white matter volume. However, there are few in vivo studies of white matter microstructural integrity (as measured using Diffusion Tensor (DT)-MRI), and nobody has related differences in white matter anatomy to schizotypy in VCFS children or adolescents. Method: We used (respectively) DT-MRI and voxel based morphometry (VBM) to measure the fractional anisotropy (FA) and proportion of white matter in 11 VCFS children and adolescents and 12 controls (7 of whom were siblings). Also, within people with VCFS we carried out a preliminary analysis in which we related differences in white matter to severity of schizotypy. Results: VCFS, compared to controls, had a significantly lower FA in frontal, parietal and temporal lobe regions as measured using DT-MRI. In contrast, FA was significantly higher than controls in the internal capsule, anterior/superior corona radiata and corpus callosum. Using VBM we found a significantly smaller proportion of white matter in the cerebellum, occipital lobes and hippocampus but a significantly higher amount in the internal capsule, basal ganglia, cingulum and corpus callosum in VCFS. Also, within people with VCFS, FA of the internal capsule was significantly positively correlated with severity of schizotypy. Conclusion: Young people with VCFS have significant differences in white matter microstructure and volume. Some, but not all of these, overlap with each other. Also, within VCFS, regional differences in FA are associated with schizotypal behaviour. [ABSTRACT FROM AUTHOR]

Background: 22q11.2 Deletion Syndrome (22q11.2 DS) is a common micro-deletion syndrome associated with intellectual disability, brain abnormalities and a complex spectrum of psychiatric disorders in both adults and children. Many previous studies have shown that adults with 22q11.2 DS have approximately thirty times greater risk for the developing schizophrenia compared to the general population. Furthermore, studies of children and adolescents with 22q11.2 DS have found high rates of psychotic symptoms, ADHD and anxiety disorders. In this study we initially aim to characterize the psychiatric and neuropsychological phenotype of all individuals in Ireland with 22q11.2 DS and then correlate our findings with genetic association studies and brain imaging. We then intend to undertake a longitudinal study to assess for risk factors of future psychotic illness. Methods: Forty-four individuals with 22q11.2 DS (Mean age = 14 years, SD = 9) were compared to 25 non-affected sibling controls (Mean age = 12 years, SD = 4). Psychiatric phenotype assessment was performed using a range of standardized clinical assessments including, the Diagnostic Interview Schedule for Children (DISC), Psychotic Supplement of K-SADS, Comprehensive Assessment of At Risk Mental State (CAARMS), the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Child Behaviour Checklist (CBCL) and the Social Communication Questionnaire (SCQ). Results: Preliminary data indicates that individuals in the 22q11.2 DS group have a higher prevalence of psychiatric disorders including; ADHD (41%), psychotic symptoms (19%), schizophrenia (2.7%), specific phobias (38%), depressive episodes (11%), and anxiety disorders (32%). Conclusion: This is the first stage in a longitudinal follow-up study of individuals with 22q11.2DS in Ireland. Our preliminary results are consistent with previous findings of high rates of psychiatric disorders in people with 22q11.2DS. The challenge remains to identify precursor symptoms in childhood that predicts the later development of psychiatric disorders, particularly schizophrenia in this vulnerable group. [ABSTRACT FROM AUTHOR]

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at ∼10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3–q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P < .05), on the basis of simulation studies. We also found two regions, 17p11.2­q25.1 (maximum LOD score [MLS] p 3.35) and 22q11 (MLS p 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P < .02) to 17p11.2­q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions. [ABSTRACT FROM AUTHOR]