Effects of a Functional COMT Polymorphism on Prefrontal Cognitive Function in Patients With 22q11.2 Deletion Syndrome
ABSTRACT The 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) is associated with attentional problems and executive dysfunction, and is one of the highest known risk factors for schizophrenia. These behavioral manifestations of 22q11.2 deletion syndrome could result from haploinsufficiency of the catechol O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype as a predictor of prefrontal cognitive function in patients with 22q11.2 deletion syndrome.
Patients with confirmed 22q11.2 deletions (N=44) underwent neurocognitive testing following Val(158)Met genotyping (Met hemizygous: N=16; Val hemizygous: N=28).
Analyses of covariance revealed that Met-hemizygous patients performed significantly better on a composite measure of executive function (comprising set-shifting, verbal fluency, attention, and working memory) than did Val-hemizygous patients.
These data are consistent with those of previous studies in normal individuals, suggesting that a functional genetic polymorphism in the 22q11 region may influence prefrontal cognition in individuals with COMT haploinsufficiency.
Full-textDOI: · Available from: Abbas F Jawad, Jul 29, 2015
- SourceAvailable from: Miri Carmel
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- "Similar results were reported by Shashi et al. (2006) and Bearden et al. (2004): Met-hemizygous 22q11.2DS children outperformed Val carriers on a composite measure of EF. "
ABSTRACT: The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.Journal of Psychiatric Research 05/2014; 56. DOI:10.1016/j.jpsychires.2014.04.019 · 4.09 Impact Factor
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- "On average people with PWS shows mild level of mental retardation, although individually their IQ scores may range from average to profoundly mentally retarded. Repeated studies since PWS had been discovered tried to establish a correlation between body mass index with IQ. No significant relation has been found. "
ABSTRACT: Mental retardation(MR) was defined by the World Health Organisation as an intelligent quotient (IQ)<70 that is accompanied by adaptive limitations in two or more key skills areas, before the age of 18. General intellectual functioning is expressed by IQ. Typically, in children younger than 5 years old who present delays in the attainment of developmental milestones at the expected age, the term of "developmental delay" is used. Also, developmental delay is used before the age of 5,when IQ testing is reliable and valid and it takes into consideration learning and adaptive deficits which predict later intellectual disability. Different classifications have been used to partition people with MR, the most frequent, accepted also by DSM IV (American Psychiatry Association) based on performances on standardised cognitive tests: mild (IQ 50-70), moderate (IQ 35-49), severe ( IQ 20-34) and profound (IQ <20). According to this type of classification the level of difficulties and everyday life needs for the social and psychological support of a person affected by MR, can be established. The definition and classification tend to accept the diagnosis of non-progressive form identifiable in small babies. In clinical practice, metabolic or neurodegenerative disorders may associate MR, frequently a progressive form, in children prior having normal development. Adrenoleukodystrophy manifests with progressive cognitive regression in boys, after a period of normal development. In addition, a pervasive developmental disorder manifested through cessation and regression of normal development, associating seizures and mycrocephaly in small girls is rather included in mental regression, only after a clear clinical picture in syndromal MR. The clinical association between MR and malformations, neurological disfunctions such as epilepsy or cerebral palsy, sensorial deficits, other maladies or behaviour disturbances are usually earlier directed to evaluation and medical care. Having such an impact on life, MR is one of the most frequent causes for genetic evaluation in babies in developped countries. Developmental screening addresses those who have developmental delays identifiable in primary care and need referral for furher evaluation.1 edited by Prof. Dr. Maria Puiu Department of Medical Genetics, University of Medicine and Pharmacy Victor Babes Timisoara, Romania, 12/2012; Intech., ISBN: 980-953-307-751-7
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- "Recent work has quantified nonverbal learning impairments in the 22q11.2DS by evaluating the behavioral endophenotypes predicted by the spatial and temporal attention model (Bearden et al., 2001, 2004a, 2005; Bish et al., 2005, 2007; Gothelf et al., 2010a; Karayiorgou et al., 2010; Kiehl et al., 2009; Simon, 2008; Simon et al., 2005a, 2005b, 2008a, 2008b; Stoddard et al., 2010; Takarae et al., 2009; Xu et al., 2010; Yamagishi and Srivastava, 2003). Individuals with the 22q11.2DS "
ABSTRACT: There is a need for refinement of the current behavioral phenotyping methods for mouse models of genetic disorders. The current approach is to perform a behavioral screen using standardized tasks to define a broad phenotype of the model. This phenotype is then compared to what is known concerning the disorder being modeled. The weakness inherent in this approach is twofold: First, the tasks that make up these standard behavioral screens do not model specific behaviors associated with a given genetic mutation but rather phenotypes affected in various genetic disorders; secondly, these behavioral tasks are insufficiently sensitive to identify subtle phenotypes. An alternate phenotyping strategy is to determine the core behavioral phenotypes of the genetic disorder being studied and develop behavioral tasks to evaluate specific hypotheses concerning the behavioral consequences of the genetic mutation. This approach emphasizes direct comparisons between the mouse and human that facilitate the development of neurobehavioral biomarkers or quantitative outcome measures for studies of genetic disorders across species.Progress in Neurobiology 02/2012; 96(2):220-41. DOI:10.1016/j.pneurobio.2011.12.001 · 10.30 Impact Factor