Article

The 22q11.2 deletion in children: High rate of autistic disorders and early onset of psychotic symptoms

Department of Psychiatry, Utrecht University, Utrecht, Utrecht, Netherlands
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 6.35). 10/2006; 45(9):1104-13. DOI: 10.1097/01.chi.0000228131.56956.c1
Source: PubMed

ABSTRACT To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS).
Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric interview, and intelligence assessment of the child. Intelligence level, psychiatric symptoms, and classification provided the main outcome.
High rates of autism spectrum disorders (30 of 60, 50.0%) and psychotic symptoms (16 of 60, 26.7%) were found in this sample. In 7 of 60 (11.7%), the psychotic symptoms interfered with behavior and caused considerable distress. In these cases, the diagnosis of a psychotic disorder was applied. The average age of the children with psychotic symptoms at time of assessment was 14.2 years. Although it is likely that the high rate of psychopathology in this sample is to some extent associated with the lower level of cognitive function, a major effect of the degree of cognitive impairment on psychiatric morbidity was not found.
Autism spectrum disorders and subthreshold autistic symptomatology are common in children with 22q11DS. Furthermore, a high rate of psychosis and psychotic symptoms is found in this childhood sample, suggesting an early onset of psychosis in 22q11DS patients. Autistic and psychotic disorders should be considered to be main elements of the behavioral phenotype of 22q11DS children.

2 Followers
 · 
174 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value = 1.27×10-32), PRODH with proline (P-value = 1.11×10-19), SLC16A9 with carnitine level (P-value = 4.81×10-14) and uncovered a novel association between DMGDH and dimethyl-glycine (P-value = 1.65×10-19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value = 1.26×10-8), KCNJ16 with 3-hydroxybutyrate (P-value = 1.65×10-8) and 2p12 locus with valine (P-value = 3.49×10-8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the genetics of complex traits.
    PLoS Genetics 01/2015; 11(1):e1004835. DOI:10.1371/journal.pgen.1004835 · 8.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, an ultrasensitive electrochemiluminescence (ECL) immunosensor was fabricated for a rapid determination of ochratoxin A (OTA) based on gold nanoparticles-hybridized mesoporous carbon (AuNPs@MC). The ECL immunosensor was constructed by modifying an anti-OTA-luminol-AuNPs@MC ionic liquid (IL) dispersion on glassy carbon electrodes. AuNPs@MC presented remarkable signal enhancement performance, and IL was adopted to increase the conductivity of the ECL immunosensor. The voltage was applied by a single-step cycle pulse method, which limited the continuous consumption of luminol and increased the stability of the ECL immunosensor. The proposed ECL immunosensor is simple, rapid, sensitive, specific, stable and reliable. Under optimum conditions, a wide detection range of 1 pg mL−1 to 50 ng mL−1 with a detection limit of 0.3 pg mL−1 was achieved. The proposed ECL immunosensor exhibited great promise in the food analysis field.
    Analytical methods 08/2014; 6(15):5766. DOI:10.1039/C4AY00833B · 1.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background 22q11.2 deletion syndrome (22q11DS) is associated with a number of physical anomalies and neuropsychological deficits including impairments in executive and sensorimotor function. It is estimated that 25% of children with 22q11DS will develop schizophrenia and other psychotic disorders later in life. Evidence of genetic transmission of information processing deficits in schizophrenia suggests performance in 22q11DS individuals will enhance understanding of the neurobiological and genetic substrates associated with information processing. In this report, we examine information processing in 22q11DS using measures of startle eyeblink modification and antisaccade inhibition to explore similarities with schizophrenia and associations with neurocognitive performance. Methods Startle modification (passive and active tasks; 120- and 480-ms pre-pulse intervals) and antisaccade inhibition were measured in 25 individuals with genetically confirmed 22q11DS and 30 healthy control subjects. Results Individuals with 22q11DS exhibited increased antisaccade error as well as some evidence (trend-level effect) of impaired sensorimotor gating during the active condition, suggesting a dysfunction in controlled attentional processing, rather than a pre-attentive dysfunction using this paradigm. Conclusions The findings from the present study show similarities with previous studies in clinical populations associated with 22q11DS such as schizophrenia that may indicate shared dysfunction of inhibition pathways in these groups.
    Journal of Neurodevelopmental Disorders 09/2014; 6(38). DOI:10.1186/1866-1955-6-38 · 3.71 Impact Factor

Full-text (3 Sources)

Download
417 Downloads
Available from
Jun 5, 2014